Novel Dynamic Foot Abduction Bar for Treatment of Clubfoot
Condition: Clubfoot
MeSH terms: Clubfoot; Talipes; Equinus Deformity
Study type: Interventional

Summary: 
      This is an assessor-blinded randomized feasibility trial evaluating a new dynamic bar for
      foot abduction bracing for clubfoot treatment. Eligible patients must have a well-corrected
      idiopathic clubfoot (Pirani Score ≤ 0.5) and be in the minimum 12 hours per day bracing stage
      of the Ponseti clubfoot treatment protocol. The overall study period will be 90 days in
      length. For the first 30 days, the experimental cohort will wear the new Dynamic Bar (DB)
      with standard ankle-foot orthoses (boots) and the control cohort will continue wearing the
      standard Straight Bar (SB). After this 30-day period, the experimental cohort will return to
      wearing their standard SB.

      All patients will be evaluated on Day 0, Day 7, Day 30, and Day 90 of the study period to
      monitor for recurrence of the clubfoot deformity, complications of brace wearing, to submit
      brace wear logs, and to complete parent-reported questionnaires regarding their perceptions
      of the Foot Abduction Brace (FAB) and their child's comfort. A minimum of 10 patients per arm
      will be recruited. A temperature sensor will be added in each participant's boots during the
      90-day study period to objectively measure time of brace wear. It is hypothesized that when
      patients are wearing the DB they will experience higher brace tolerance defined as increased
      wear time of the brace as measured by the temperature sensors, and higher comfort levels as
      reported by parents, without an increase in clubfoot deformity recurrence compared to the SB.
    

Detailed description: 
      Primary objective:

      To evaluate the ease of recruiting and retaining participants for a randomized-controlled
      effectiveness trial of a novel FAB bar.

      Primary endpoint:

      Recruitment rate, dropout rate, and related responses on the parent-reported survey.

      Secondary objectives:

        1. To compare parental perception of the child's comfort in the SB versus the DB for foot
           abduction bracing in Ponseti clubfoot treatment.

        2. To compare patient tolerance of the SB to the DB as measured by parent self-reporting
           and by how many hours the brace is worn per day as recorded by temperature sensors
           placed in the boots.

        3. To perform a preliminary assessment of the effectiveness of the DB at preventing
           clubfoot recurrence during the bracing phase when the brace is worn as prescribed for a
           30-day trial period.

      Secondary endpoints:

        1. Patient comfort levels determined by parent-reported surveys with 5-point Likert scale
           responses completed at Day 0, Day 30, and Day 90 of the study period.

        2. Daily brace wear hours as measured by a parent self-reported log and by temperature
           sensors implanted inside the boots.

        3. Presence of clubfoot recurrence defined as a Pirani score > 0.5 representing any new
           development of cavus, adduction and/or hindfoot varus, or a loss of passive ankle
           dorsiflexion (equinus) of < 10 degrees above neutral or a reduction of 5 or more degrees
           from the previous visit.

           Clubfoot patients are normally reviewed in clinic every 3-6 months. If scheduling
           permits, Day 0 of the study period will align with patient's already scheduled follow up
           visit. All patients will therefore require either 3 or 4 extra visits (possibly on Day
           0, and surely on Day 7, Day 30, and Day 90). These extra visits will consist of the same
           evaluations done in the routine clubfoot monitoring protocol, in addition to the
           study-related questionnaire, brace wear log, video recording (on Day 30 only), and
           temperature sensor data collection.

           Three surveys will be administered to parents on Day 0, Day 30, and Day 90 of the study
           period. These surveys will be collected and managed using REDCap (Research Electronic
           Data Capture) hosted at SickKids. Parents will also be asked to complete a brace wear
           log to be submitted at Day 30 and Day 90 of the study period.

           Most patient information that will be reviewed in this study is data being collected and
           stored per the REB-approved Clubfoot Research Registry protocol (REB #1000053919). All
           patients enrolled in study this will also be enrolled in Clubfoot Research Registry, if
           not already enrolled.

           Each patient will be assigned a unique study ID. Patients will be assigned to an arm by
           drawing lots. This will be done by preparing 20 opaque, sealed envelopes. 10 of these
           envelopes will contain the word "Experimental," and the remaining 10 will contain the
           word "Control." On Day 0 of the study period, each participant will choose an envelope
           at random, and be assigned to that arm. This technique will ensure that the ratio
           between patients in each arm is 1:1.

           To minimize bias, the outcomes assessor, who is an advanced practice physiotherapist
           clubfoot provider, will be independent of the study and design teams and blinded, so
           they will not know which bar has been assigned to which patient.

           To ensure that the outcomes assessor remains blinded, a member of the study team will
           check in the patient at the beginning of each visit, remind the patient and parent about
           the blinding, and ensure that the bar is removed and hidden from view before the outcome
           assessor enters the evaluation room.

           Unblinding may occur for any participant who has experienced an adverse event, such as
           clubfoot recurrence, and must return to their original SB, if not already using it.
           Unblinding will occur for all participants if any severe adverse event occurs that is
           related to the use of the DB. For unblinding to occur, the outcomes assessor must notify
           a member of the study team, and any member of the study team may unblind the outcomes
           assessor.

           All intentional and unintentional breaking of the blind will be documented in the
           study's enrollment log, along with the reason(s) for unblinding. Per protocol, the Data
           Safety Monitoring Board and Research Ethics Board will also be notified of any adverse
           events or unblinding.

           Participation in this trial is completely voluntary and parents may choose not to
           participate and may withdraw at any time. If parents choose to withdraw, this will be
           noted in the study enrollment log and their collected data will be deleted upon request.

           As an incentive for visit attendance, all participants will receive $20 CAD for each
           extra clinical visit (possibly on Day 0, and surely on Day 7, Day 30, and Day 90 of the
           study period) as reimbursement for travel expenses, given on the day of the final study
           visit.

           STUDY INTERVENTIONS An example of a standard SB is the Ponseti bar, which is a rigid,
           metal bar that clips on and off of the patient's boots by means of a patented "Quick
           Clip" mechanism. This bar is available in 3 sizes, depending on the patient's shoulder
           width. Designated as a class 1 medical device, this bar is used as standard care for
           clubfoot treatment.

           The DB prototype is a 3-part bar, consisting of a crossbar with two L-shaped components
           on each end, which connect to the boots by the same "Quick Clip" mechanism. Each
           L-component is connected to the crossbar via a low friction slider, which allows for
           independent axial translation perpendicular to the crossbar, and a modified ball joint
           linkage, which allows for independent sagittal rotation.

           The ball joint linkages also provide a small amount of independent axial and coronal
           rotation. This provides the patient with extra ankle dorsiflexion and abduction up to a
           maximum of 30 degrees in each direction. This allows for added movement through the knee
           and hips, reduces strain at the patient's joints, and reduces stress concentration at
           the hinges of the bar. The ball joint linkages therefore reduce potential discomfort for
           the patient and reduce the chance that the bar will break while in use.

           The L-components are machined using 5052-H32 aluminum and have a soft protective end cap
           to reduce the risk of any unintentional self-injuries. The crossbar and sliders are 3D
           printed using medical grade ABS plastic. They are attached using adhesive, two steel
           ball joint linkages, and various fasteners made out of steel and brass.

           Ideal foot position for clubfoot is approximately 10 degrees of ankle dorsiflexion, and
           60 degrees of external rotation with the feet held shoulder-width apart. This position
           is maintained as the DB is pre-bent to provide 10 degrees of ankle dorsiflexion, the
           external rotation can be adjusted with bolts, and the length of the bar can be adjusted
           with set screws. While the DB provides extra mobility, the ball joint linkages prevent
           patients' ankle dorsiflexion of less than 10 degrees and abduction of less than 60
           degrees at all times during use. We anticipate that providing patients with more ankle
           dorsiflexion and external rotation than required will have no negative effects on
           patient outcomes.

           Both bars are compatible with the same boots.

           STUDY INTERVENTION COMPLIANCE Standard care for clubfoot treatment is to assess bracing
           compliance by asking the parent about the patient's daily wear time at each scheduled
           appointment. Studies have shown that parents over-report brace wear by approximately
           30%. In order to objectively measure bracing compliance, a temperature sensor will be
           added in each patient's boots during the 90-day study period.

           The temperature sensors that will be used are the DS1921G-F5 Thermochron iButtons,
           designed and manufactured by iButtonLink Technology in Wisconsin, USA. Each device is a
           battery powered data logger equipped with a temperature sensor. The devices will be set
           to record the temperature of the boots' insoles every 45 minutes and launched on Day 0
           and Day 30 on the study period. The device complies with medical standards and is
           calibrated against a National Institute of Standards and Technology (NIST) traceable
           source. Thermochron iButtons have previously been used in a similar clubfoot bracing
           adherence study. The data obtained from these temperature sensors will be used to
           calculate the daily brace wear time of each patient during the interventions, by
           measuring the temperature increase when the child is in the brace.

           For unilateral clubfoot cases, the temperature sensor will be placed in the boot that
           holds the clubfoot. For bilateral cases, the sensor will be placed on the right boot. To
           implant each sensor, technicians at SickKids will drill a hole through the sole of the
           boot and insert the iButton with an interference fit. This hole will be located directly
           over top of the slider in the "Quick Clip" mechanism, so that the slider secures the
           sensor and prevents it from falling out. The insole of the boot will be then covered
           with a layer of ShearBan® in order to ensure patient comfort and to ensure that the
           temperature sensor never comes into contact with skin. ShearBan is a self-adhesive film
           often used in insoles and orthopaedic braces. This procedure mimics that of another
           clubfoot brace compliance study, for which an installation video has been created.

           The orthotics department will ensure that implantation of the iButton does not
           compromise the fit or function of the boots. Depending on the size and model of the
           participant's current boots, each participant will either receive a new boot that is
           pre-fitted with an iButton sensor, or the iButton sensor will be inserted into their
           current boot on Day 0 of the study period. If a new boot was given, the study team will
           collect this boot on Day 90 of the study period, and the participant will return to
           their original boot.

           To launch and retrieve data from the temperature sensors, a member of the study team
           will have to briefly remove the sensor from the boot on Day 0, Day 30, and Day 90 of the
           study period. When reinserting the sensor, the research team will ensure that the hole
           is re-covered with a layer of ShearBan.

           If the participant is using their original boots and the parent wishes to remove the
           sensor after the study is complete, the research team will remove the sensor and cover
           the hole with a layer of ShearBan.

           Participants are free to withdraw from participation in the study at any time upon
           request.

           STUDY ASSESSMENTS AND PROCEDURES The physical exam that will be performed at each study
           visit will be done according to standard care for clubfoot. The only physical
           assessments that are not part of standard clubfoot care is measuring the patients' tibia
           length to ensure appropriate fit of the DB, as well as measuring the patients' height
           and weight to explore any possible reasons for bar malfunction or breakage. The height
           and weight of each participant will be measured and recorded by the blinded outcome
           assessor, with or without help of the clinic nurse, who routinely collects this data at
           SickKids.

           To quantify parent perception and feedback, three different surveys will be administered
           to the parents/caregiver at scheduled times throughout the trial. This includes a survey
           at Day 0, Day 30, and Day 90 of the study period. Surveys will be completed in-person at
           the time of clinic visits, or via email after the visit if there was insufficient time
           to collect the data.

           The purpose of the first survey on Day 0 is to assess parental perception of the
           standard SB prior to the study period. For the experimental arm, the second survey will
           assess parental perception of the new DB immediately after 30 days of wear, and the
           third survey will assess parental impression of returning to the SB after use of the DB
           at Day 90. For the control arm, the Day 30 and 90 surveys will serve as a test-retest
           reliability measure from Day 0 to assess if any variation over time (due to change in
           foot shape, treatment, recurrence, or environment) can be detected.

           ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS An Adverse Event (AE) is any untoward medical
           occurrence associated with the use of an intervention in a study participant, which does
           not necessarily have a causal relationship with the intervention. An AE can therefore be
           any unfavourable and unintended sign, symptom or disease temporally associated with the
           use of the DB, whether or not considered related to the investigational intervention.

           Stable chronic conditions which are present prior to entry in the study and do not
           worsen are not considered AE. These pre-existing conditions will be documented in the
           participant's medical history.

           We do not foresee any SAEs occurring that are related to the use of the DB. That being
           said, all SAEs will be documented and reported for any incident that:

             1. is related to a failure of the dynamic bar or a deterioration in its effectiveness,
                or any inadequacy in its directions for use; and

             2. has led to the death or a serious deterioration in the state of health of a
                patient, user or other person, or could do so were it to recur. "Serious
                deterioration in the state of health" means: a life-threatening disease, disorder
                or abnormal physical state; the permanent impairment of a body function or
                permanent damage to a body structure; or a condition that necessitates an
                unexpected medical or surgical intervention to prevent such a disease, disorder or
                abnormal physical state or permanent impairment or damage.

           Known risks associated with all standard bars include pressure sores, skin rashes,
           unintentional self-injuries, and clubfoot recurrence for suboptimal brace wear or
           application.

           We anticipate that the same risks are associated with the dynamic bar prototype, in
           addition to the risk of bar malfunction or breakage due to lack of extensive material
           evaluations, and an increased risk of clubfoot recurrence due to the unprecedented
           mobility provided to patients.

           If any of these events occur during the study, they will be documented in the patient's
           chart, and on REDCap as specified by the Clubfoot Research Registry protocol. These
           events might also result in the participant being withdrawn from the study or
           temporarily discontinued from the study intervention.

           It should be noted that pressure sores may break skin. While patients are encouraged to
           wear socks with their boots, if they choose to not wear socks, this may result in the
           ShearBan adhesive, which will be placed on top of the temperature sensor inside the
           boot, coming into contact with intact or non-intact skin.

           The severity of an AE will be assessed by the study team's physiotherapists and/or PI,
           who will use the following definitions when assessing the intensity of an AE:

             -  Mild - Events require minimal or no treatment and do not interfere with the
                participant's daily activities.

             -  Moderate - Events result in a low level of inconvenience or concern with the
                therapeutic measures. Moderate events may cause some interference with functioning.

             -  Severe - Events interrupt a participant's usual daily activity and may require
                systemic drug therapy or other treatment. Severe events are usually potentially
                life-threatening or incapacitating. Of note, the term "severe" does not necessarily
                equate to "serious".

           The only "severe" AE that is foreseen to potentially occur during the study is clubfoot
           recurrence. Clubfoot recurrence would likely be treated by serial casting, as is
           standard care for clubfoot treatment. Mild to moderate AEs may potentially include
           pressure sores, skin rashes, and unintentional self-injuries. All of these AEs are known
           risks associated with FABs.

           All Adverse Events (AEs) will have their relationship to the DB assessed by the study
           team's physiotherapists and/or PI based on temporal relationship and their clinical
           judgment. The degree of certainty about causality will be graded using the categories
           below.

             -  Definitely Related - There is clear evidence to suggest a causal relationship, and
                other possible contributing factors can be ruled out. The clinical event occurs in
                a plausible time relationship to study intervention administration and cannot be
                explained by concurrent disease or other drugs or chemicals. The response to
                withdrawal of the study intervention should be clinically plausible.

             -  Probably Related - There is evidence to suggest a causal relationship, and the
                influence of other factors is unlikely. The clinical event occurs within a
                reasonable time after administration of the study intervention, is unlikely to be
                attributed to concurrent disease or other drugs or chemicals, and follows a
                clinically reasonable response on withdrawal.

             -  Possibly Related - There is some evidence to suggest a causal relationship (e.g.,
                the event occurred within a reasonable time after administration of the study
                intervention). However, other factors may have contributed to the event (e.g., the
                participant's clinical condition, other concomitant events).

             -  Unlikely to be related - A clinical event whose temporal relationship to study
                intervention administration makes a causal relationship improbable (e.g., the event
                did not occur within a reasonable time after administration of the study
                intervention) and in which other drugs or chemicals or underlying disease provides
                plausible explanations (e.g., the participant's clinical condition, other
                concomitant treatments).

             -  Unrelated - The AE is completely independent of study intervention administration,
                and/or evidence exists that the event is definitely related to another etiology.

           All unexpected AEs will be reported to The Hospital for Sick Children Research Ethics
           Board according to The Hospital for Sick Children's Adverse Event Reporting
           Requirements.

           TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP All AEs and SAEs occurring
           while on study will be documented regardless of relationship. Information to be
           collected will include event description, date of onset, date of resolution, outcome,
           and the assessment of seriousness, expectedness, relationship to study intervention, and
           severity by the study team's physiotherapists and/or PI.

           Any baseline condition recorded in the medical history that deteriorates at any time
           during the study, will be recorded as an AE or SAE.

           Changes in the severity of an AE will be documented to allow an assessment of the
           duration of the event at each level of severity to be performed.

           Events will be followed for outcome information until resolution or in the opinion of
           the study team's physiotherapists and/or PI, the participant is stable and does not
           require further follow-up, or the participant is deemed lost to follow-up.

           Participants and/or their parent/legal guardian will be informed in a timely manner of
           any new information, including safety information, that is relevant to that
           participant's willingness to continue participation. The communication of this
           information will be documented through a revised REB approved Informed Consent Form,
           where possible, based on the timeliness of the information.

           SAMPLE SIZE DETERMINATION The intent of this study is to obtain preliminary data on the
           current prototype and evaluate the feasibility of conducting a larger-scale clinical
           trial. Therefore, only a minimum of 10 patients will be enrolled in each arm.

           In a future effectiveness randomized controlled trial, we plan to use a sample size of
           124, with 62 patients per arm. This sample size will ensure that the study has
           sufficient statistical power to detect a minimal clinically detectable difference in
           recurrence rates of at least 20% between the SB and DB group. Note this is assuming that
           the recurrence rates in the control arm will be 30%, as reported recurrence rates after
           correction range from 20-41% (6). This power analysis was conducted based on 80% power
           and 5% type 1 error.

           The Clubfoot Clinic at SickKids sees approximately 35 patients per week. Based on the
           frequency of clinical visits required for patients at different stages in the Ponseti
           treatment, it is expected that approximately 15% of these patients will be between the
           ages of 1 and 3 and in the minimum 12-hour per day bracing stage of the Ponseti
           treatment. Furthermore, approximately 80% of all clubfoot patients are idiopathic, and
           it is expected that 75% of eligible patients will be willing to participate in the trial
           (22). Therefore, it is foreseen that it will take approximately 2 months to register all
           20 participants.

           POPULATIONS FOR ANALYSES

           The following study populations are defined and will be analyzed as specified below:

             -  Intent to treat population: the total population of patients registered in the
                study.

             -  Experimental arm population: all registered participants in the experimental arm
                with DB.

             -  Control arm population: all registered participants in the control arm with SB.

             -  Safety population: all registered participants who wore their FAB as prescribed for
                the full 90-day study period.

             -  Brace discomfort population: all registered participants who have any history of
                brace intolerance or indicated in the parent-reported survey that they are not
                comfortable/have concerns with their original FAB.

             -  Brace comfort population: all registered participants who have no history of brace
                intolerance and indicated in the parent-reported survey that they are
                comfortable/have no concerns with their original FAB.

           STATISTICAL ANALYSES All data will be deidentified before analysis. Due to the small
           sample size, the analysis will consist of descriptive statistics, as defined in terms of
           means, standard deviations, and percentile ranks where applicable.

           ANALYSIS OF THE PRIMARY ENDPOINT Parent-reported comfort levels will be determined by
           parent-reported surveys with 5-point Likert scale responses. Results from these surveys
           will be analyzed with descriptive statistics for the intent to treat population, the
           brace discomfort population, and the brace comfort population. The enrollment log will
           also record the age and fit issues of patients that do not adequately fit the available
           prototype but are otherwise eligible. This will serve to inform future adaptations of
           the new DB for future trials.

           ANALYSIS OF THE SECONDARY ENDPOINTS Daily bracing times will be measured by a
           temperature sensor added in each patient's boots for the entire 90-day study period. The
           number of hours the brace is worn per day will be divided by the standard number of
           desirable hours in brace (12 hours) in order to obtain a fraction that quantifies the
           patient's adherence to the FAB. Mean 'adherence fractions' will be calculated for
           patients in each arm, and then compared using descriptive statistics. This analysis will
           be performed for the intent to treat population, the brace discomfort population, and
           the brace comfort population. This data will be compared to the self-reported brace wear
           hours by parents in their daily logs.

           To ensure minimal efficacy of the DB prototype, all signs of clubfoot recurrence will be
           carefully examined at each study visit. The null hypothesis is that 'the dynamic bar
           does not lead to higher rates of clubfoot recurrence,' and it will be rejected if the
           number of patients in the safety population that develop clubfoot recurrence during the
           90-day study period, is substantially greater in the experimental arm than it is in the
           control arm (i.e. more than 2 instances of clubfoot recurrence in the experimental arm
           than in the control arm). Note that this endpoint is not intended to prove safety or
           efficacy, but rather to ensure that the design may prevent early recurrence before a
           larger-scale trial is conducted. Clubfoot recurrence is defined as a Pirani score > 0.5,
           a new occurrence of cavus, adduction and/or hindfoot varus, or a loss of passive ankle
           dorsiflexion (equinus) of < 10 degrees above neutral or a reduction of 5 or more degrees
           from the previous visit. Note that all clinical tests required to diagnose recurrence
           are routinely performed as standard clubfoot care.

           If consent is provided by the parents, a member of the study team will also record a
           video of each patient wearing their prescribed bar on Day 30 of the study period. These
           videos will be closely studied to compare the range of motion provided by the SB to the
           DB, and to verify that the DB consistently maintains proper foot position during use.
           Videos will be recorded on a password-protected personal device, audio will be removed,
           then the video will be uploaded each day to the patient's REDCap forms. The video will
           then be deleted from the personal device. All efforts will be made to made to only
           include the patient's feet and legs in the field of the video, and to blur or remove any
           identifiable physical marks like unique birthmarks and tattoos on the patient's skin.

           SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS This study may be temporarily
           suspended or prematurely terminated if there is sufficient reasonable cause. Written
           notification, documenting the reason for study suspension or termination, will be
           provided by the suspending or terminating party to study participants and the REB. Study
           participants will be contacted, as applicable, and be informed of changes to study visit
           schedule.

           Circumstances that may warrant termination or suspension include, but are not limited
           to:

             -  Determination of unexpected, significant, or unacceptable risk to participants by
                use of the dynamic bar

             -  Insufficient compliance to protocol requirements

             -  Data that are not sufficiently complete and/or evaluable

             -  Determination of futility

           The study may resume once concerns about safety, protocol compliance, and data quality
           are addressed, and satisfy the Sponsor and REB.

           All research activities will be conducted in as private a setting as possible.

           Study data will be entered into REDCap, a secure, web-based application designed
           exclusively to support data capture for research studies. The application and data are
           housed on servers provided by the Hospital for Sick Children. These servers are located
           within SickKids secure data center.

           Most patient health information that will be analyzed for this trial will be collected,
           stored, and destroyed as specified by the Clubfoot Research Registry (REB #1000053919).
           The clinical evaluations performed at each study visit will be standard care.

           A separate electronic enrollment log will track enrollment of patients by MRN number and
           name and assign a study ID to those patients that consent to participate in the trial.
           Data collected will not link to participants' OHIP number.

           Patient confidentiality will be ensured except when legally required. Only members of
           the research team will have access to the research data. Any data exported for
           statistical analysis will be de-identified. All identifying information will be kept
           behind 2 security measures or as per equivalent institutional policy, under the
           supervision of the PI and will not be transferred outside of the hospital.

           To enable evaluations and/or audits from the Sponsor or REB, the Principal Investigator
           agrees to keep records, including all original signed informed consent forms, consent
           discussion forms, the enrollment log, and surveys in a secure location for a minimum of
           7 years in accordance with SickKids policy. Subsequently, all identifying data will be
           destroyed.
    

Intervention name(s): Foot abduction bracing for clubfoot with novel dynamic bar; Foot abduction bracing for clubfoot with standard straight bar
Intervention type(s): Device; Device
Intervention description(s): After Ponseti treatment of serial casting and tenotomy for clubfoot, patients are braced full time x 3 months then night time until age 5. This study compares the standard straight bar in a foot abduction brace to our novel dynamic bar. This group uses the novel bar.; After Ponseti treatment of serial casting and tenotomy for clubfoot, patients are braced full time x 3 months then night time until age 5. This study compares the standard straight bar in a foot abduction brace to our novel dynamic bar. This group uses the standard bar.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Experimental arm with new device, control arm with standard device.
Masking: Single (Outcomes Assessor)
Primary purpose: Device Feasibility