Aim, design and setting
The study design is that of a single-blind prospective randomized comparison of two splinting methods for patients who have undergone zone II flexor tendon repair. The treating hand therapist and the patient are aware of the treatment regimen but the assessing hand therapist (brought in for the 6 week and 12 week assessments) is specifically not aware of the splint used and remains ‘blinded’ to that information. The study is a single-center study that will inform development of a future multicenter study and is clinically based within the hand trauma service that serves a major conurbation and sees just under 4000 cases annually.
Primary and secondary outcomes
The primary endpoint is Total Active Motion (TAM) measured by goniometer at 6 weeks and 12 weeks (assessed separately). The secondary endpoints comprise patient reported outcomes at 6 and 12 weeks and grip strength measurement at 12 weeks. It is important to establish that the short splint is not worse than the long splint in terms of rupture rates. As rupture is a relatively rare event– (4-6% incidence in recent reported series) it would require a substantial sample size to power the comparison and it is therefore not a primary endpoint. We envisage a narrative description that would reflect on the ruptures within the context of published literature and say whether the rupture rate fell within or outside these published norms.
Characteristics of participants – recruitment to study
All patients who have sustained zone II flexor tendon injury and also meet the inclusion criteria of the study will be assessed by a site investigator (surgeon) for their potential suitability for the study and if appropriate will be invited to participate.
The detailed inclusion and exclusion criteria are presented in Table 1. These criteria include both patient factors and injury factors.
Table 1 Inclusion and exclusion criteria
INCLUSION CRITERIA
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EXCLUSION CRITERIA
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Adult patient (16 yrs or older)
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Children under 16 yrs of age
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Single Zone II flexor tendon division with or without FDS division. Includes single nerve injury on same digit.
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Patients with special needs and vulnerable groups
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Time interval of injury to operation <96 hours (4 days)
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Patients lacking capacity or motivation to participate in planned physiotherapy
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Patients unable to attend physiotherapy for requisite number of sessions for social and economic reasons
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Patients unable to understand English sufficient to complete rehabilitation
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Flexor tendon injury greater than 4 days previous
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Two digital nerve injuries in the same finger as the flexor tendon injury
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More than one finger with FDP injury
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Multilevel FDP injury in one finger
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Complex injury with soft tissue defect
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Complex injury with underlying fracture
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Processes, interventions and comparisons
The specific intervention is to test the use of a short splint against the long dorsal forearm splint that is normally used to protect zone II flexor tendon repairs. Figure 1 illustrates the two splint designs with the traditional long dorsal splint (Fig.1A Dorsal view and Fig 1B lateral view) and the short splint (Fig. 1C Dorsal view and Fig 1D lateral view). The timelines, and assessments are detailed in SPIRIT Figure 2. This includes some modifications to the traditional exercise regime specifically to engage wrist movement and take advantage of the tenodesis phenomenon that passively increases interphalangeal joint extension. Detailed measurements are taken at 6 and 12 weeks into treatment in all patients by an assessing 'blinded' therapist who is not party to which splint has been used (in all patients the splint is discontinued at 6 weeks). The frequency of visits to the hand therapy department is the same for both groups so there are no extra attendances as a result of participation in the trial.
Patients are counselled and invited to participate in the trial by a site investigator who is a member of the surgical team. The patient is provided with Patient Information Leaflet (Appendix 1). Actual recruitment only then takes place at the first attendance to the hand therapy department when a therapist who is a site investigator goes through the counselling and consent for the trial and answers questions the patient may have. A Patient Consent Form is also completed at this time.
The surgery that is undertaken is by the standard protocol of the department and is not affected by this study. This protocol is for a 4-strand core suture using 3/0 prolene and a 5/0 epitendinous suture with adequate venting of the pulleys of the flexor tendon sheath. We are only concerned in this study with the aftercare.
It is normal practice to see the flexor tendon patients 4-5 days after surgery to commence rehabilitation. The patients in the study will have had this period of time to consider whether they wish to participate or not. If they choose to join the study then subsequent randomization proceeds as follows. Block randomization is used to ensure that equal numbers of patients are allocated to the control and trial groups with block sizes of 4 patients in each. The allocation sequence is randomly generated using the randomization software (www.randomizr.org). The treatment sequence is then sequence coded so the so the site investigators do not know the upcoming allocation of the patients. This is designed to deliver equipoise and obviate the possibility of recruitment bias.
Concealment is assured as the hand therapist undertaking assessment at the 6 week and 12 week assessment points is not present whilst the splint is being worn. The treating therapist then removes the splint at 6 weeks and the patient is instructed not to reveal which splint they have used as they move across to the assessing therapist. The patient and the hand therapist at randomization/splint application are not blinded to treatment allocation and hence the trial is by definition single blind. Patients who choose not to enter the study receive the traditional long splint. Patients in both groups are treated by an experienced team of specialist hand therapists who will supervise their rehabilitation.
A patient who has initially given consent to participate but then loses capacity or chooses to withdraw consent to participate is withdrawn from the study. In practice this means that a patient in Group B (short splint) converts to traditional splinting any time within the first 6 weeks after operation. A patient in Group A (long dorsal splint) continues with that splint but does not undergo the specific assessments of the study.
Follow up arrangements are the same for each group and all patients are required to attend therapy clinic once each week for the first 6 weeks and undertake specified exercises as part of routine care. Following removal of the splint at 6 weeks, a program of exercise, soft tissue stretching and night splinting for any residual contracture is initiated. Patients in both groups are permitted to return to normal activities at 12 weeks. From 6 weeks onwards once the splint is removed the treatment of all patients, regardless of Group is the same.
The rehabilitation protocol for both groups is that of early combined passive flexion and active motion exercises. The exercise sequence emphasizes full passive flexion stretches to maximize passive digital motion prior to commencing active motion. Active flexion exercises are initiated from the distal interphalangeal (DIP) joint to maximize differential glide. Patients are encouraged to perform active flexion exercises carefully to minimize the work of flexion. They are encouraged to perform active digital extension exercises to minimize the occurrence of interphalangeal joint flexion contractures. Furthermore, patients are discouraged from performing excessive or forced active flexion at the end range of motion.
Patients in group A (long dorsal splint) perform digital flexion and extension exercises within the splint keeping the wrist in neutral and MCP joints at 30o flexion position. In contrast Patients in group B (short splint) perform active digital flexion exercises with the wrist extended to 45° and active digital extension exercises with the wrist in maximal flexion with the MCP joints at 30o flexion.
In both groups, palmar thermoplastic finger splints will be provided for use at night in those patients who are unable to achieve full interphalangeal joint extension and therefore have incipient fixed flexion tendency notably of the proximal interphalangeal joints.
All patients will be given instructions on the safe and light functional use of their hands, excluding the injured digit(s). The patients will be instructed to wear their splints for a period of 6 weeks.
Assessment is undertaken at 6 weeks and on completion of treatment at 12 weeks by the ‘blinded’ hand therapist who is one of the site investigators. The primary outcomes are the range of motion of PIPJ and DIPJ of the affected finger (Total Active Motion) at 6 weeks and 12 weeks. Secondary outcome measures comprise Visual Analogue Scale for pain score, PEM, Quick DASH patient questionnaire, and grip strength all at 6 and 12 weeks with the exception of grip strength which is only tested at 12 weeks. In addition the absence of tendon rupture is a further secondary outcome in this study. The number and duration of visits to the hand therapy department is the same for both groups. The study duration is from the time the patient is first seen in the Hand Therapy clinic post-surgery and completes at 12 weeks for the patient. All measurements and adverse events are recorded in the participants’ Case Report Forms.
Adverse events are recorded in the patients’ Case Report Forms and depending on the particular form of adverse event will be notified or actioned as follows and in line with Good Clinical Practice protocols. The treating hand therapist will communicate any event, complication or other concern to one of the hand therapists acting as site investigators to the trial. The site investigator will initially decide whether the reported event is likely to be, or could potentially be, associated with the trial intervention and assign attribution. Adverse events will be notified to the Principal Investigator and any Serious Adverse Events notified directly to the Principal Investigator and within 24 hours to the trial sponsor. Any trial participant suffering serious adverse event will be followed up and onward referral to an appropriate clinician made, as clinically indicated. There is potential for serious adverse device effect (SADE) related to the short splint of which there may be anticipated serious adverse device effect (ASADE) - for example increased incidence of rupture of repair and unanticipated serious adverse device effect (USADE). As the splint material itself is the same for both splint patterns it is not anticipated that there would be any biological reaction to the splint material such that the chance of a serious unexpected serious adverse reaction (SUSAR) is minimal.
Thus surgical wound infection may be categorized as an adverse event that is not causally related to the splint conformation but rather to injury and surgical factors. Tendon ruptures may or may not be related to the splint conformation and would be categorized as SADE given that further surgery is normally required to effect a rerepair. Patients affected in this way will still continue on the trial and have their data collected. Flexor tenolysis performed at a later date for poor glide of the tendon repair due to adhesions would not be performed during the trial period, but only at a later date, and are therefore not reported within the timeline of the trial. Any earlier surgical interventions occurring within the 12 week trial timeline would be recorded in the Case Report Form.
Table 2 details the assessments, investigations and interventions undertaken by the hand therapists with comparison on which parts of the pathway represent additional items that would not otherwise be part of routine treatment .
Table 2 Details of assessments and interventions undertaken by the hand therapists
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First postoperative visit (within 5 days of flexor tendon repair operation)
*Recruitment into trial with counselling regarding same by the investigating hand therapist. Trial consent form is completed and patient is randomized to short splint (intervention) or long dorsal splint (control)
Fashioning of thermoplastic splint. Advice to patient on exercises to be undertaken including safe use of the hand.
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Patient reviewed weekly thereafter at 2,3,4, and 5 weeks as part of standard care by treatment hand therapist. During visit the patient is further advised and undertakes supervised exercises by the treating hand therapist. Integrity and glide of tendon repair are assessed. Same for trial and non-trial patients.
*Trial patients – any adverse events are reported in CRF having been notified to a site investigator
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6 week review. Splint is discontinued and removed by the treating hand therapist. Advice is given on driving and return to normal activities of daily living and sporting and recreational activities. The treating hand therapist then hands over to the assessing hand therapist (site investigator) who is ‘blinded’ as to which splint has been used. The assessing hand therapist is a different one from the therapist who recruited the patient initially to the trial. Assessing hand therapist measures range of motion of the affected finger is made and recorded using goniometer. Also measures contralateral finger range of motion to allow calculation of the TAM as a percentage of what is normal for that patient. Integrity and glide of tendon repair are assessed. Data is recorded.
*Trial patients have their measurements performed by an assessing hand therapist after removal of the splint (single blind protocol). Any adverse events are reported in CRF. In addition the PEM, Quick DASH and VAS PROMs scales are administered and recorded in the CRF.
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12 week review. Patients who attend will have their range of motion and grip strength recorded using Jamar dynamometer on the second setting (mean of 3 separate recordings of grip). Integrity and glide of tendon repair are assessed. Data is recorded.
*Trial patients have their measurements performed by an assessing hand therapist (single blind protocol). Any adverse events are reported in CRF In addition the PEM, Quick DASH and VAS PROMs scales are administered and recorded in the CRF.
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*Comments in italics highlight those parts of the pathway representing additional items that would not otherwise be part of routine treatment
The assessment by the site investigator hand therapist includes :
- Quick DASH, PEM
- pain scales (Numerical Analogue Scale 0-10)
- range of motion of injured digit proximal and distal interphalangeal joint range of motion using digital goniometer
- grip strength at 12 weeks using Jamar dynamometer on 2nd setting (power grip is not tested earlier to avoid potential tendon rupture)
Trial management
The trials team meet regularly to review conduct and progress of the trial and to ensure trial documentation is maintained in compliance with GCP requirements. The Principal Investigator will be responsible for submitting trial amendments to the Research and Ethics Committee for approval, providing regular trial progress reports and notifying completion of trial. Once approved, any trial changes and accompanying documentation will be relayed to the site investigators and Clinical Trials Management teams by the Principal Investigator. The Clinical Trials Management team will have an independent reviewer to undertake site visit to monitor trial conduct, compliance and documentation (approximately annually).
The investigating team are scientifically independent from the sponsor (Trust). The responsibility for interim analyses and stopping guidelines will be with the trials team and Principal Investigator with advice from the trial statisticians.
Recruitment strategies include regular educational updates for new members of the surgical team to act as site investigators. Our research nurse will assist with identification of potential participants based around the morning trauma meeting. The departmental trauma coordinator and trauma clinic nurses will also assist in case identification but will not be involved in actual recruitment to the trial. In addition regular review of reasons for non-recruitment of potential patients will be undertaken. Retention of trial patients once on study is recognized to be important and this will be supported through the continuity of high level care in the hand therapy department. Patients who do not attend an appointment will be phoned once to offer a further appointment.
Trial ethical approval has been obtained form the Research Ethics Committee 14/NW/1486 IRAS project ID 159054.
The Trust as sponsor is acting for ancillary and post-trial care as the need arises.
Statistical analysis and power calculation
Advice on statistical analysis was obtained from our medical statistician at Manchester University Foundation Hospitals Trust. With respect to primary analysis of TAM : a two-sample t-test will be used for comparing TAM of the injured finger at 6 and 12 weeks. In order to detect a difference in mean TAM of 20o (SD 30o) with 90% power and a 5% significance level, a sample size of n=37 will be required for each group. Accounting for a realistic drop-out rate of 20% of participants over the course of the study this sample size would have to be adjusted to n=47 for each group making a total for planned recruitment of 94 participants. This calculation is based on data from our previously published audit Peck et al 2014 (5). Secondary analysis will be performed and continuous outcomes will be compared using two-sided two-sample t-tests, or a nonparametric Mann-Whitney U test if the Normality assumption is not satisfied on review of the data. Categorical outcomes including will be compared using a Chi-squared or Fisher’s exact test as appropriate. All statistical tests will be performed at the 5% significance level using SPSS software.
Interim analysis
An interim analysis will not be carried out, as this is a small scale exploratory trial to investigate the effectiveness of the new short splint. Early stopping for futility is unlikely as the new splint did not appear to perform worse than the control splint in our previous audit (Peck et al, 2014). There will be no issue of multiple testing as there are not multiple primary outcomes. On the point of potential missing data, the sample size has been increased to account for this.
Data management
The study protocol is designed in compliance with standard Caldicott and GDPR regulations. Patients recruited and consented to the study are notified to the Local Portfolio Management System and recorded on R-PEAK. Special patient identifier numbers will be generated for each participant’s Case Report Form (CRF) and used to identify patients through the study. No names or dates of birth are used with respect to data entry to the study. Data collection is manual and this raw data is then transcribed into Excel held on Trust computer. The CRF hard copy files will be maintained on site consistent with regulations. The raw data transcription into electronic format will be undertaken by member of the hand therapy team. Primary data will be processed on Trust computers by the authors and secondary data transported without patient identifiers on encrypted pen drives. Processed data will be stored on home computers of the authors of the research study and will be the subject of peer review presentation and publication so will be communicated electronically at this stage.
Trial data management is subject to regular audit trail led by Clinical Trials Management team of the Trust. The auditor is independent of the trial investigating team.
Post study the full participant data will be stored for less than 12 months from the conclusion of the study (electronic and hard copy). Processed data will be stored in the Hand Therapy department files. Lead Hand Therapist (DB) will have access to the same and the processed data (electronic and hard copy) will be destroyed after 10 years. There are no specific plans to facilitate public access to the final trial dataset but this will be available on reasonable request from the Principal Investigator (VL).
Finally, publication of the results will be sought in peer-reviewed journal with presentation at national meetings. Summary of results will be communicated to participants by letter. The results will also be reviewed with our Patient and Public Involvement and Engagement group (PPIE).