Self-Myofascial Release Intervention and Mobile App in Patients With Hemophilic Ankle Arthropathy: Protocol for a Randomized Controlled Trial

Background Hemophilic ankle arthropathy is manifested by degenerative functional alterations and chronic pain. Myofascial release techniques are used to treat soft tissue adhesions, relieve pain, and reduce tissue sensitivity. Objective This study aims to evaluate the safety and efficacy of a protocol using self-myofascial release with a foam roller to be applied in patients with hemophilic ankle arthropathy. Methods Patients with ankle arthropathy (N=70) will be recruited, enrolled, and assigned to one of two groups—experimental or control—in a 1:1 allocation ratio. Patients will be recruited from 5 centers in different regions of Spain. Patient data will be collected at baseline, posttreatment, and follow-up. The primary outcome will be frequency of ankle joint bleeding (self-reported). The secondary outcomes will be ankle range of motion (measured with a digital goniometer); joint pain (measured with a visual analog scale and an algometer); joint status (measured using the Hemophilia Joint Health Score); muscle strength (measured with a dynamometer); functionality of lower limbs (measured using the 6-minute walking test); activity (self-reported); and muscle flexibility (measured using the fingertip-to-floor test). The treatment program includes 11 exercises that must be administered bilaterally. A mobile app will be developed where each patient will be able to observe the exercises to be carried out. Each session will last 15 minutes with 5 physiotherapy sessions per week for a period of 3 months. It is expected that patients with hemophilia who receive the foam roller intervention will show improvement in mobility, pain, and status of the ankle joint; muscle strength; and function in the lower extremities. Results The study has been approved by the institutional review board of the University of Murcia. Patient recruitment will begin in September 2020, and the intervention period will last until June 2021. Data collection will take place between September 2020 and October 2021. Conclusions This protocol describes a randomized clinical trial to examine the safety and efficacy of a self-myofascial release intervention using a foam roller in patients with hemophilic ankle arthropathy. Trial Registration ClinicalTrials.gov NCT03914287; http://clinicaltrials.gov/ct2/show/NCT03914287. International Registered Report Identifier (IRRID) PRR1-10.2196/15612

URL of your Intervention Website or App e.g. a direct link to the mobile app on app in appstore (itunes, Google Play), or URL of the website. If the intervention is a DVD or hardware, you can also link to an Amazon page.
Tu respuesta URL of an image/screenshot (optional) Tu respuesta Accessibili ty * Can an enduser access the intervention presently? Primary Medical Indication/Disease/Conditi on * e.g. "Stress", "Diabetes", or define the target group in brackets after the condition, e.g. "Autism (Parents of children with)", "Alzheimers (Informal Caregivers of)" Primary Outcomes measured in trial * comma-separated list of primary outcomes reported in the trial Secondary/other Are there any other outcomes the intervention is expected to affect? subitem not at all 1 2 3 4 5 essential 1a-i) Identify the mode of delivery in the title Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-webbased Internet components (e.g. email), use "computerbased" or "electronic" only if offline products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms.
Does your paper address subitem 1a-i? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 1a-ii) Non-web-based components or important cointerventions in title Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support").
Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta 1a-iii) Primary condition or target group in the title Mention primary condition or target group in the title, if any (e.g., "for children with Type I Diabetes") Example: A Web-based and Mobile Intervention with Telephone Support for Children with Type I Diabetes: Randomized Controlled Trial Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study subitem not at all important 1 2 3 4 5 essential 1b-ii) Level of human involvement in the METHODS section of the ABSTRACT Clarify the level of human involvement in the abstract, e.g., use phrases like "fully automated" vs. "therapist/nurse/care provider/physician-assisted" (mention number and expertise of providers involved, if any). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) Does your paper address subitem 1b-ii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta 1b-iii) Open vs. closed, web-based (selfassessment) vs. face-to-face assessments in the METHODS section of the ABSTRACT Mention how participants were recruited (online vs. offline), e.g., from an open access website or from a clinic or a closed online user group (closed usergroup trial), and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment). Clearly say if outcomes were self-assessed through questionnaires (as common in web-based trials From September 2020 to June 2021, 70 patients with ankle arthropathy will be recruited to randomized clinical trial. Participants will be assigning to one of two groups: experimental group (n = 35) and control group (n = 35). Patients will be recruited in 5 centers, from different regions of Spain. Patient´s will be collected at baseline, posttreatment and follow-up period. Primary outcome will be frequency of ankle joint bleeding (self-reported). Secondary outcomes will be ankle range of motion (digital goniometer); joint pain (visual analog scale and algometer); joint status (Haemophilia Joint Health Score); muscle strength (dynamometer); functionality of lower limbs (6-Minute Walking test); activity record; and muscle flexibility (Finger-floor test). The treatment program includes 11 exercises that must be administered bilaterally. A mobile application will be developed where each patient will be able to observe the exercises to be carried out. Each session will last 15 minutes, with five physiotherapy sessions per week for a period of 3 months.
subitem not at all important (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not For Self-Myofascial release, patients use their own body weight on a foam roller or on the lower limbs to exert pressure on the affected soft tissues [20,21]. Scientific evidence shows that these types of tools help improve the range of motion and pre and post exercise muscle performance [21,22]. The effectiveness of these types of exercises to improve joint mobility has been tested by authors such as MacDonald et al. [20] in relation to improving mobility in knee flexion, and by Skarabot et al. [23] relative to the improvement of ankle joint mobility.
The myofascial system possibly responds to the use of foam rollers based on post-intervention changes in joint range of motion and pressure pain thresholds. These changes may be due to a mechanical and neurophysiological response [24,25]. The direct pressure of the roller may produce a local mechanical and global neurophysiological effect relaxing the tissues and reducing pain in the target and surrounding area [26].
Local pressure from the roller may affect the viscoelastic properties of myofascia which may be responsible for such changes.
Other mechanisms that may be involved include thixotropy (reduced viscosity), myofascial restriction, fluid-related changes, and cellular responses [24].
Researchers have also found that foam-rolling reduces arterial stiffness, increases arterial tissue perfusion, and improves vascular endothelial functions related to tissue relaxation [27].
The object of this paper is to detail our approach to the design and implementation of this protocol for self-myofascial release using a Foam Roller applied in patients with hemophilic ankle arthropathy looking to reduce the frequency of joint bleeding and improve variables such as range of motion, joint pain, functionality, joint state, and muscle flexibility and strength.
3b) Important changes to methods after trial commencement (such as eligibility criteria), with reasons subitem not at all important 1 2 3 4 5 essential 4a) Eligibility criteria for participants applicable/relevant for your study Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 3b-i) Bug fixes, Downtimes, Content Changes Bug fixes, Downtimes, Content Changes: ehealth systems are often dynamic systems. A description of changes to methods therefore also includes important changes made on the intervention or comparator during the trial (e.g., major bug fixes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have influenced study design such as staff changes, system failures/downtimes, etc. [2].
Does your paper address subitem 3b-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study A randomized, multicenter clinical trial in patients with hemophilia and ankle hemophilic arthropathy. Figure 1 presents an overview of the study. The primary aim of this randomized trial (ClinicalTrials.gov NCT03914287) is to establish the safety and effectiveness of a physiotherapy intervention through self-myofascial release using a Foam Roller. Once eligibility is be determined, participants will be randomized either to the intervention arm (experimental group) or the control group.

Not available
subitem not at all important 1 2 3 4 5 essential subitem not at all important 1 2 3 4 5 essential 4a-i) Computer / Internet literacy Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clarified.
Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 4a-ii) Open vs. closed, webbased vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. offline), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were faceto-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasianonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email confirmation, phone calls) were used to detect/prevent these.
Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

Tu respuesta
The inclusion criteria to participate in the present study are patients: diagnosed with hemophilia A and B disease; over 18 years-old; diagnosed with bilateral hemophilic arthropathy of the ankle (more than three points of joint damage on the Hemophilia Joint Health Score); and on prophylactic or on demand treatment with FVIII/FIX concentrates. Patients who will be excluded from the study are those: without ambulation ability; with inhibitors (antibodies to FVIII or FIX); with neurological or cognitive alterations that prevent understanding the questionnaires and physical tests; and who have failed to sign the informed consent document.
After obtaining the patients' informed consent, the baseline assessments will be carried out at the relevant centers of the Hemophilia Associations included in the study.
subitem not at all important 1 2 3 4 5 essential 4b) Settings and locations where the data were collected subitem not at all important 1 2 3 4 5 essential 4a-iii) Information giving during recruitment Information given during recruitment. Specify how participants were briefed for recruitment and in the informed consent procedures (e.g., publish the informed consent documentation as appendix, see also item X26), as this information may have an effect on user self-selection, user expectation and may also bias results.
Does your paper address subitem 4a-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta Does your paper address CONSORT subitem 4b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 4b-i) Report if outcomes were (self-)assessed through online questionnaires Clearly report if outcomes were (self-)assessed through online questionnaires (as common in web-based trials) or otherwise.
Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study After obtaining the patients' informed consent, the baseline assessments will be carried out at the relevant centers of the Hemophilia Associations included in the study. Each patient will perform the interventions at home.
Measurements will be performed by a physiotherapist blinded to patient assignment. After the treatment period and at 3 months following completion, the patients included in both groups (experimental and control) will be reevaluated by the same rater, under the same conditions as the initial evaluation. Seven dependent variables (range of motion, joint pain, functionality, joint state, muscle strength and flexibility, and activity record) will be measured at the various study assessment times (baseline, post-treatment and follow-up). The outcome measures used for these variables will be: -Visual analogic scale (VAS). This scale will be used to evaluate the perception of joint pain, where ankle joint pain ranges from 0 to 10 points (no pain to maximum perceived pain).
-Pressure algometer (model Wagner FPN100, Wagner Instruments, CT, USA). Measuring instrument used for the assessment of pressure pain, both at the joint and remote sites (in other parts of the body) [28]. This device uses Newton/cm2 to measure the pressure point at which the subject perceives pain upon pressure. Pressure will be made on the chosen site, gradually increasing at an approximate speed of 50kPa/s until the patient reports that the sensation is becoming painful [29]. In patients with ankle arthropathy, bilateral measurements will be 4b-ii) Report how institutional Report how institutional affiliations are displayed to potential participants [on ehealth media], as affiliations with prestigious hospitals or universities Measurements will be performed by a physiotherapist blinded to patient assignment. After the treatment period and at 3 months following completion, the patients included in both groups (experimental and control) will be reevaluated by the same rater, under the same conditions as the initial evaluation. Seven dependent variables (range of motion, joint pain, functionality, joint state, muscle strength and flexibility, and activity record) will be measured at the various study assessment times (baseline, post-treatment and follow-up). The outcome measures used for these variables will be: -Visual analogic scale (VAS). This scale will be used to evaluate the perception of joint pain, where ankle joint pain ranges from 0 to 10 points (no pain to maximum perceived pain).
-Pressure algometer (model Wagner FPN100, Wagner Instruments, CT, USA). Measuring instrument used for the assessment of pressure pain, both at the joint and remote sites (in other parts of the body) [28]. This device uses Newton/cm2 to measure the pressure point at which the subject perceives pain upon pressure. Pressure will be made on the chosen site, gradually increasing at an approximate speed of 50kPa/s until the patient reports that the sensation is becoming painful [29]. In patients with ankle arthropathy, bilateral measurements will be taken ventral to the lateral malleolus (ankle) [30]; and at two remote points distant from the ankle: on the spinous process of L5 and at the extensor carpi radialis longus (on the forearm, 5 cm distal to the lateral epicondyle of the humerus) [ . This measuring instrument will be used to evaluate the joint condition of knees, ankles, and elbows. It includes 8 items (inflammation and its duration, pain, atrophy and muscle strength, crepitus, and reduced flexion and extension) ranging from 0 to 20 points per joint (the higher the score, the greater the joint deterioration).
-6-Minute Walking test (6-MWT) [33]. The 6-MWT test is a performance-based test that measures walking speed and the submaximal capacity to perform an exercise. This instrument was developed for use in patients with respiratory disease and heart failure but has been used in children and adults with a variety of chronic conditions, including hemophilia [34][35][36]. Patients are instructed to walk along a 30 to 50-meter track for 6 minutes attempting to cover as much distance as possible without running. The distance traveled in 6 minutes is recorded, allowing the use of a walking aid or orthopedic devices. -Digital goniometer. Ankle range of motion shall be measured using a digital goniometer according to protocol rules designed by Thornton et al. [37]; the assessment can be made with the patient standing. The axis of the goniometer will be placed parallel to the external malleolus of the ankle. The fixed arm will be parallel to the fibula, while the mobile arm parallel to the fifth metatarsal bone. This measuring instrument allows more accurate measurements than those obtained with a universal plastic goniometer. The patient will be asked to perform three repetitions of each movement. -Dynamometry. The maximum isometric strength of the plantar flexor muscles of the ankles will be evaluated on both limbs with a manual dynamometer. The patient will be placed in supine position with his or her foot arranged at 90º of dorsal flexion. The dynamometer will be located proximal to the metatarsophalangeal joints on the plantar side). The patient will be asked to perform 3 isometric maximum 5-second contractions, with a 30-second break between them, against the dynamometer held by the evaluator [38]. . This test is used to assess the degree of flexibility of the posterior muscles of the lower limbs. The value is calculated as the distance between the fingertip and the floor when maximum hip flexion with knee extension is performed. Does your paper address subitem 5-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 5-ii) Describe the history/development process Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results.
Copy and paste relevant sections from the manuscript Each session will last approximately 15 minutes, with five physiotherapy sessions over a period of 3 months. The Self-Myofascial release protocol for the lower limbs using a Foam Roller and Solid Ball Massage, adapted to patients with hemophilic ankle arthropathy, will include self-myofascial release of the plantar region, back of the leg, hamstring region, and adductor, abductor and pelvitrochanteric muscles. Does your paper address subitem 5-ii?
(include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta

5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial. Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b).
Does your paper address subitem 5-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 5-iv) Quality assurance methods Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable.
Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta 5-v) Ensure replicability by publishing the source code, and/or providing Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture Each session will last approximately 15 minutes, with five physiotherapy sessions over a period of 3 months. Each patient will perform the interventions at home. The Self-Myofascial release protocol for the lower limbs using a Foam Roller and Solid Ball Massage, adapted to patients with hemophilic ankle arthropathy, will include self-myofascial release of the plantar region, back of the leg, hamstring region, and adductor, abductor and pelvitrochanteric muscles. Table 1 shows the Physiotherapy protocol used in patients with hemophilic ankle arthropathy.
subitem not at all important Does your paper address subitem 5-v?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login.
Does your paper address subitem 5-vi?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of specific group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).
Does your paper address subitem 5-vii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for Does your paper address subitem 5-viii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum.
Participants will have free access, downloading the mobile app, without having to be members of any group. Access to the platform was approved after signing the informed consent. Once the study is complete, the contents of the application (Table 1) will be posted on the website (www.inhefis.org.) Participants will have free access, downloading the mobile app, without having to be members of any group. Access to the platform was approved after signing the informed consent. Once the study is complete, the contents of the application (Table 1)  Does your paper address subitem 5-ix?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the eintervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21 -generalizability).
Does your paper address subitem 5-x?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta 5-xi) Report any prompts/reminders used Report any prompts/reminders used: Clarify if there were prompts (letters, emails, phone calls, SMS) to use the application, what triggered them, frequency etc. It may be necessary to distinguish between the level of prompts/reminders required for the trial, and the level of prompts/reminders for a routine application outside of a RCT setting (discuss under item 21 -generalizability).
Does your paper address subitem 5-xi? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for Participants will have free access, downloading the mobile app, without having to be members of any group. Access to the platform was approved after signing the informed consent. Once the study is complete, the contents of the application (Table 1)  Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta 6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed If outcomes were obtained through online questionnaires, describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were A periodic follow-up will be made, through phone calls and SMS, to answer questions from patients regarding the use of the application, etc.
Subjects included in the control group will receive no physical therapy through self-myofascial release and will continue with their usual routine of physical activity and exercise, following the same pharmacological treatment regimen with FVIII/FIX. At the end of the study period the intervention will be applied under the same conditions as the experimental group, analyzing the overall sample at the end of the study.
subitem not at all important Tu respuesta -Visual analogic scale (VAS). This scale will be used to evaluate the perception of joint pain, where ankle joint pain ranges from 0 to 10 points (no pain to maximum perceived pain).
-Pressure algometer. Pressure will be made on the chosen site, gradually increasing at an approximate speed of 50kPa/s until the patient reports that the sensation is becoming painful [29]. In patients with ankle arthropathy, bilateral measurements will be taken ventral to the lateral malleolus (ankle) [30]; and at two remote points distant from the ankle: on the spinous process of L5 and at the extensor carpi radialis longus (on the forearm, 5 cm distal to the lateral epicondyle of the humerus) [28]. register [31]. Using a portable instrument for assessing physical activity, the patient's level of physical activity and main related variables (average number of steps per day, average distance per day, average amount of active time and energy consumption) shall be recorded.
-Hemophilia Joint Health Score (HJHS). It includes 8 items (inflammation and its duration, pain, atrophy and muscle strength, crepitus, and reduced flexion and extension) ranging from 0 to 20 points per joint (the higher the score, the greater the joint deterioration).
-Minute Walking test (6-MWT) [33]. This instrument was developed for use in patients with respiratory disease and heart failure but has been used in children and adults with a variety of chronic conditions, including hemophilia [34][35][36]. Patients are instructed to walk along a 30 to 50-meter track for 6 minutes attempting to cover as much distance as possible without running. The distance traveled in 6 minutes is recorded, allowing the use of a walking aid or orthopedic devices.
-Digital goniometer. The axis of the goniometer will be placed parallel to the external malleolus of the ankle. The fixed arm will be parallel to the fibula, while the mobile arm parallel to the fifth metatarsal bone. This measuring instrument allows more accurate measurements than those obtained with a universal plastic goniometer. The patient will be asked to perform three repetitions of each movement.
-Dynamometry.The patient will be placed in supine position with his or her foot arranged at 90º of dorsal flexion. The dynamometer will be located proximal to the metatarsophalangeal joints on the plantar side). The patient will be asked to perform 3 isometric maximum 5-second contractions, with a 30-second break between them, against the dynamometer held by the evaluator [38]. . The value is calculated as the distance between the fingertip and the floor when maximum hip flexion with knee extension is performed. 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group 8b) Type of randomisation; details of any restriction (such as blocking and block size) 9) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

No Yes
For those patients who, fulfilling the study selection criteria, wish to voluntarily participate in the study, a random assignment using opaque envelopes will be made to each of the two study groups: experimental group and control group. Random assignment of patients will be carried out after cluster recruitment (based on hemophilia type and age) to ensure greater homogeneity of the study groups. This assignment will be carried out by a person not involved in the study objectives and always unaware of the identity of the subjects included in the study.
10) Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions 11a) If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering cointerventions (if any).
Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 11a-ii) Discuss e.g., whether participants knew which intervention was the Informed consent procedures (4a-ii) can create biases and certain expectations -discuss For those patients who, fulfilling the study selection criteria, wish to voluntarily participate in the study, a random assignment using opaque envelopes will be made to each of the two study groups: experimental group and control group. Random assignment of patients will be carried out after cluster recruitment (based on hemophilia type and age) to ensure greater homogeneity of the study groups. This assignment will be carried out by a person not involved in the study objectives and always unaware of the identity of the subjects included in the study.

Yes
After obtaining the patients' informed consent, the baseline assessments will be carried out at the relevant centers of the Hemophilia Associations included in the study. Measurements will be performed by a physiotherapist blinded to patient assignment.
subitem not at all important 1 2 3 4 5 essential 11b) If relevant, description of the similarity of interventions (this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed "intervention of interest" and which one was the "comparator" e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator".
Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 12a-i) Imputation techniques to deal with attrition / missing Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how subitem not at all important 1 2 3 4 5 essential values participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).
Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

X26-i) Comment on ethics committee approval
The main descriptive statistics will be obtained (mean and standard deviation) of the evaluations carried out for all the dependent variables. An ANOVA of partially repeated measures will be carried out to compare the two groups (experimental and control) at the three assessment times: baseline (T0), posttreatment (T1) and follow-up (T2). When the interaction is significant, pairwise comparison tests will be performed on the group factor and on the repeated measurements factor. To control the significance level of error rate, the Bonferroni correction method will be applied. The results of the F test depend on the significance of Mauchly's sphericity test. If significant, the Greenhouse-Geisser correction will be used. To assess clinical relevance, we will calculate the standard error of measurement (SEM) and minimal detectable change (MDC) for each dependent variable.
We will use the intent-to-treat method to include all subjects who were randomized in the final data analysis.

RESULTS
13a) For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center Does your paper address subitem X26-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study x26-ii) Outline informed consent procedures Outline informed consent procedures e.g., if consent was obtained offline or online (how? Checkbox, etc.?), and what information was provided (see 4a-ii). See [6] for some items to be included in informed consent documents.
Does your paper address subitem X26-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta X26-iii) Safety and security procedures Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline) Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta Does your paper address subitem 15-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 16-i) Report multiple "denominators" and provide definitions Report multiple "denominators" and provide definitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at specific pre-defined time points of interest (in absolute and relative numbers per group). Always clearly define "use" of the intervention.
Does your paper address subitem 16-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study

16-ii) Primary analysis should be intent-to-treat
Primary analysis should be intent-to-treat, secondary analyses could include comparing only "users", with the appropriate caveats that this is no longer a randomized sample (see 18-i).
Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Table 2   Table 3 17a) For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) subitem not at all important 1 2 3 4 5 essential 17b) For binary outcomes, presentation of both absolute and relative effect sizes is recommended Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 17a-i) Presentation of process outcomes such as metrics of use and intensity of use In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational definitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is defined (e.g., timeout after idle time) [1] (report under item 6a).
Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta Does your paper address CONSORT subitem 17b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study  Tables 4 and 5 For those patients who, fulfilling the study selection criteria, wish to voluntarily participate in the study, a random assignment using opaque envelopes will be made to each of the two study groups: experimental group and control group. Random assignment of patients will be carried out after cluster recruitment (based on hemophilia type and age) to ensure greater homogeneity of the study groups. This assignment will be carried out by a person not involved in the study objectives and always unaware of the identity of the subjects included in the study.

Yes
subitem not at all important

20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error.
Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events.
Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study The goal of the study is to evaluate the safety and effectiveness of a protocol related to self-myofascial release with a Foam Roller when used in patients with hemophilic ankle arthropathy. This project is the most ambitious physiotherapy study in terms of methodology recorded to date. The recruitment of 70 patients with hemophilia from 5 different regions for participation in a Physiotherapy program confers this project an extraordinary statistical power in a rare pathology such as hemophilia. Patients with hemophilic ankle arthropathy will receive treatment based on self-myofascial release using a Foam Roller. Coordination among different regions of Spain, with the participation of Universities, Hospitals and Associations of patients, is an uncommon effort in the field of hemophilia-related Physiotherapy research. The research team is made up of multidisciplinary hemophilia specialists. Renowned physiotherapists with extensive clinical experience and researchers in the field of hemophilia, as well as experts in methodology and statistics, make up a highly competitive and efficient multidisciplinary team.
Another potential strength of this protocol is to demonstrate the safety and efficacy of self-myofascial release with a Foam Roller for the treatment of hemophilia ankle arthropathy. This protocol can help to establish a rapid, safe and effective intervention for these patients.
In addition to the clinical improvement, it would favor a greater adherence to physiotherapeutic treatment and a better perception of quality of life. Self-myofascial release using a Foam Roller requires no economic investment in cases of manual therapy. Validating its safety and efficacy could promote the development of a quick, inexpensive and simple physiotherapy intervention, easily achieving a widespread use. Generalizability to other populations: In particular, discuss generalizability to a general Internet population, outside of a RCT setting, and general patient population, including applicability of the study results for other organizations Does your paper address subitem 21-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta 21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other co-interventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting.
Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Tu respuesta Does your paper address CONSORT subitem 23? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study 24) Where the full trial protocol can be accessed, if available 25) Sources of funding and other support (such as supply of drugs), role of funders X27) Conflicts of Interest (not a CONSORT item) subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 24? * Cite a Multimedia Appendix, other reference, or copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Does your paper address CONSORT subitem 25? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study X27-i) State the relation of the study team towards the system being evaluated In addition to the usual declaration of interests (financial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention.
Does your paper address subitem X27-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briefly explain why the item is not applicable/relevant for your study Registration: Clinicaltrials.gov NCT00102401 Table 1 The study has been approved by the Ethics Committee of the University of Murcia (ID: 2428/2019). Patient recruitment will begin in September 2020, with an intervention period until June 2021. Data collection will take place between September 2020 and October 2021, recruiting 70 patients with hemophilia. Otro: STOP -Save this form as PDF before you click submit To generate a record that you filled in this form, we recommend to generate a PDF of this page (on a Mac, simply select "print" and then select "print as PDF") before you submit it.
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