A Randomized Controlled Trial of Leg Length Discrepancy Techniques

Study Overview
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Brief Summary
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This is a randomized clinical trial of epiphysiodesis techniques: percutaneous transphyseal screw epiphysiodesis versus percutaneous drill epiphysiodesis for the correction of leg length discrepancy. Failed epiphysiodesis was selected as the primary outcome. Failed epiphysiodesis was defined as one or more of the following: development of angular deformity > 5°, revision epiphysiodesis, or growth inhibition < 70% of expected. EOS, low dose biplanar X-Ray, will be used to make all length measurements. Secondary outcomes assess mean growth at the physis following epiphysiodesis, in the subset of patients with bead implantation, fluoroscopy and operative times, length of stay, return to full weight bearing, as well as functional and quality of life outcomes. The following outcome scales will be used to measure pain (VAS), quality of life (PROMIS Pediatric Pain Interference Scale), and function (PROMIS Pediatric Mobility Scale, Pedi-FABS, and UCLA Activity Score). Each of these scales has been validated for use in children (Beyer, Denyes, & Villarruel, 1992; DeWitt et al., 2011; Fabricant et al., 2013; Novais et al., 2014; Varni et al., 2010a). We will also determine the cost associated with each technique and perform a cost-effectiveness analysis to establish which technique is preferred from a societal perspective.

Detailed Description
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Drill and screw epiphysiodesis are the two most common techniques for surgical correction of predicted limb length discrepancies 2-5cm. Both procedures require minimal incisions, less than 1cm, (Canale & Christian, 1990; Metaizeau et al., 1998). Previous studies have demonstrated that both drill and screw epiphysiodesis result in improved outcomes compared to open techniques (Alzahrani, Behairy, Alhossan, Arab, & Alammari, 2003; Canale & Christian, 1990). Moreover, alternative approaches such as medial and lateral 8 plates may not sufficiently tether growth, or cause peripheral but not central growth arrest (Stewart et al., 2013). We selected drill vs. screw epiphysiodesis as the two treatment groups as they are both minimally invasive, relatively effective, in common usage, and are thought to differ in costs and other characteristics. Although outcomes of drill and screw epiphysiodesis exist{{10 Campens,C. 2010; 11 Ghanem,I. 2011}} , the assessments are retrospective non-randomized series, which may be at risk for selection bias, and may not adequately capture all of the outcomes of interest, depending on what data is routinely collected and documented in the medical chart. To our knowledge, no prospective randomized comparison of epiphysiodesis techniques and clinical outcomes has been published accurately assessing how effective each technique is in disabling growth at the physis, or taking into account patient-centered outcomes or cost. Operative measures such as the surgical time and radiation exposure from intra-operative fluoroscopy have not previously been compared. Patient-centered outcomes such as level of pain, activity, and function by measures such PROMIS and Ped-FABS, have not been previously assessed in this population. The proposed research study aims to fill this gap. This study was designed as a multicenter randomized trial to answer an important clinical question and to do so with a clearly defined objective and validated outcomes. This trial can be executed on a relatively small budget with simple outcome measures, and recruitment of a moderate number of patients at each of a few centers well equipped for research. By involving multiple surgeons and patients from various geographies, we improve the generalizability of this study. Our institution and collaborating institutions have been successful in completing randomized clinical trials in the past. This study will answer a clinical question that is important and current, providing orthopedic surgeons with an evidence-based identification of the ideal technique for treating predicted limb length discrepancies 2-7cm. This study will also be the first to accurately measure mean growth following both epiphysiodesis techniques, through implantation of tantalum beads in consenting participants. These beads will provide stationary landmarks by which growth can be measured directly, and not inferred. Previous methods of judging epiphysiodesis success have primarily relied on assessing efficacy by estimating growth inhibition through calculation. Tantalum beads have been successfully used in adults and children (Lauge-Pedersen,H. 2006), and although it requires implantation of small radio-opaque beads, it is considered the gold standard when making detailed radiographic measures, and the optimal technique for physeal growth measurements.(Lauge-Pedersen,H. 2006)(Haugan,K. 2012). Over 300 000 beads have been inserted in vivo without significant complications.

Official Title
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PEDS Trial: Percutaneous Epiphysiodesis, Drill Versus Screws for Leg Length Discrepancy A Randomized Clinical Trial

Conditions
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Leg Length Discrepancy

Intervention / Treatment
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* Device: Tantalum Beads & Injector
* Procedure: Percutaneous Drill Epiphysiodesis
* Procedure: Percutaneous Screw Epiphysiodesis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Open growth plates Skeletally immature requiring isolated complete epiphysiodesis of the distal femur and/or proximal tibia At least one year of predicted growth remaining Less than 18 years of age Predicted limb length discrepancy 2-7 cm Exclusion Criteria: Patients undergoing additional orthopedic procedures at time of epiphysiodesis Metabolic bone disease or sick physis syndrome, that may cause bone to grow in an unpredictable manner. Pregnancy

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Percutaneous Drill Epiphysiodesis<br>A 5 mm incision will be made centered over the physis both medially and laterally. A 4.5 mm drill will be passed repeatedly across the physis in a divergent manner. Curettes will then be used to further remove and disrupt the growth plate. Fluoroscopy will be used throughout to ensure proper passage of the drill and curettes. Omnipaque dye will then be inserted to confirm ablation of the physis. | Device: Tantalum Beads & Injector<br>* To measure growth at physis, four tantalum beads will be implanted per physis at baseline and take radiostereometric analysis measurements at all follow up timepoints. Tantalum beads have been used to make detailed three dimensional radiographic measurements in orthopedic and other specialties<br>* Other names: 500 RSA ®Tantalum Markers diameter 0.8mm or 1.0mm;Procedure: Percutaneous Drill Epiphysiodesis<br> <br> |
| Experimental: Percutaneous Screw Epiphysiodesis<br>In the distal femur, guide wires will be placed in an antegrade fashion, with an 8 mm skin incision proximal to the physis both medially and laterally. The guide wire will be placed with the medial wire crossing the physis at the junction of the middle and medial third of the physis. The lateral guide wire will cross the physis at the junction of the lateral and middle third of the physis. The wires will extend into the epiphysis, but will not enter the joint. The guide wires will be over drilled with a 5 mm drill, and 7.3 mm fully threaded cannulated screws will be placed across the growth plate. For tibias, screw placement will be retrograde, with 8 mm incisions made medially and laterally distal to the physis, with guide wires aiming proximally. | Device: Tantalum Beads & Injector<br>* To measure growth at physis, four tantalum beads will be implanted per physis at baseline and take radiostereometric analysis measurements at all follow up timepoints. Tantalum beads have been used to make detailed three dimensional radiographic measurements in orthopedic and other specialties<br>* Other names: 500 RSA ®Tantalum Markers diameter 0.8mm or 1.0mm;Procedure: Percutaneous Screw Epiphysiodesis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure of Epiphysiodesis | development of angular deformity > 5°, revision epiphysiodesis, or growth inhibition < 70% of expected | 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Physeal Growth | Distance between tantalum beads. | Baseline, 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 
| Time to Baseline Pain | Visual Analog Scale | Baseline, 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 
| Quality of Life | PROMIS Pain Interference and Mobility | Baseline, 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 
| Length of Hospital Stay | participants will be followed for the duration of hospital stay (discharge date - admission date) | An expected average of 2 days | 
| Time to full weight-bearing | Documenting the number of days until patient could weight-bear without using devices as crutches or wheelchairs. | 2- 6 weeks | 
| Need for Splint or Cast | Documenting days worn. | 2- 6 weeks | 
| Days Until Return to Sports | Documenting how many days elapsed before the patient returned to sports. This information will be recorded in a post-operative pain and function diary. Return to sports is typically surgeon driven, but timing for return to sports is not standardized in clinical practice. In the current study patients will be allowed to return to sports when pain free, no longer limping and strength is equivalent to the non-operative side | 2-6 weeks | 
| Need for Secondary Surgery | Assessed in follow up clinical visits and documented in clinical records | 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 
| Physical Activity Level | Pediatric activity scale assessment measured by HSS Pedi-FABS. | Baseline, 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 
| Physical Activity Level | UCLA Activity Scale | Baseline, 2-6 weeks, 6 months, 12 months, 24 months, and 60 months | 
| Complications | Complications will be tracked for two years post surgery. Due to previous research, which is outlined below, the following complications will be included in the data collection follow up sheets: angular deformity, revision surgery, time until return to sports, hospital stay, failure/incomplete epiphysiodesis, time until weight bearing, infection, use of aid, number of days using the aid, and osteochondral damage. | 2-6 weeks, 6 months, 12 months, 24 months, and 60 months | 
| Medical Costs | Costs will be collected through hospital administration. In hospital costs and outpatients costs will be included. Indirect costs, such as lost days of parental work will not be considered. Only costs from the United States centers in this protocol will be assessed. | 5 years (end of study) | 
| Operative Outcomes | radiation, total time during surgery, skin dose, blood loss, surgeon experience, epiphysiodesis technique, fluoroscopy time | intra-operative | 
| Radiographic Assessments | Mechanical Tibial-Femoral Angle, Mechanical Axis Deviation, mLDFA, MPTA, PPTA | Baseline, 2-6 weeks, 5-7 months, 11-13 months, 23-25 months, 59-61 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCT, Epiphysiodesis, Tantalum beads, Patient centered outcome data, Cost effective analysis