Clinical trial NCT05516849: Placebo Versus Oxandrolone Supplementation in Trauma
Official title: Placebo Versus Oxandrolone Supplementation in Trauma: A Randomized Multi-Center Double Blind Clinical Trial in High-Energy Lower Extremity Trauma (POST-Injury Trial)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Trauma Injury
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Walter Reed National Military Medical Center
First posted: 2022-08-26
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using a minimal sufficient randomization technique in REDCAP.
Primary purpose: TREATMENT

Brief summary: The primary aim of this study is to examine the effect of Oxandrolone supplementation after lower extremity high energy fracture on muscle volume recovery. As Oxandrolone supplementation has never been examined in this patient population, the primary null hypothesis is that there will be no difference in measured thigh muscle mass volume between Oxandrolone supplementation and placebo administration groups.

Detailed description: Lower extremity fractures associated with high-energy mechanisms of injury (combat injuries including blast or crush injuries, motor vehicle accidents, fall from significant height, gunshot injuries) are unfortunately common among active service members and civilians presenting to level-1 trauma centers worldwide. High-energy fractures have several unique characteristics that distinguish them from low-energy injuries. They typically occur in predominately younger, male patients (30-65 years old)1 and involve significant soft-tissue stripping or damage. These patients require at least one major reconstructive surgery, with the majority requiring multiple reconstructive surgeries, each associated with additional soft tissue injury and subsequent prolonged immobilization to facilitate limb stabilization. Despite extended rehabilitation focused on neuromuscular retraining and muscular development, the result is often permanent limitations of ambulation and medical retirement from active duty due to volumetric muscle loss. So, while advances in orthopedic approaches to fracture care have lowered complications such as non-union and malunion, rendering them less significant as limitations to restoring function soft-tissue complications now predominate.

Oxandrolone has been successfully utilized to accelerate muscular recovery, reduce muscle loss, and improve function in several populations including healthy elderly patients with frailty/sarcopenia, patients with large surface area burns, neuromuscular diseases, HIV, congenital heart disease and genetic diseases including Klinefelter's and Turner's Syndromes. In addition, Oxandrolone has also been safely used in pediatric patients to treat constitutionally delayed growth. Given the similarities in patient populations and the known limitations of volumetric muscle loss in military personnel and civilians after major trauma, Oxandrolone supplementation may reduce initial volumetric muscle loss and improve long-term muscle mass and function.

Eligibility criteria: Inclusion Criteria:

1. Male
2. Ages 18-55 \[inclusive\]
3. Skeletally-mature as based upon tibial or femoral physeal closure41
4. Fracture of the femur or tibia treated with open reduction and internal fixation (simple articular patterns allowed).
5. High energy injuries with associated local soft tissue damage. -

Exclusion Criteria:

1. Unable to participate in rehabilitation including severe head injury, pre-existing TBI or cognitive dysfunction (stroke, dementia, documented developmental delay), patients with significant spinal cord injury or pre-accident paralytic injury or condition will beessential treatment in both intervention and control groups.
2. Medically unfit for anabolic steroid treatment including those with active malignancy, concurrent prednisone use, elevated liver enzymes at baseline (baseline bloodwork to include LFT)
3. Fracture due to primary or metastatic bone lesion
4. Any contraindications to MRI.
5. Patients with major psychiatric illness \[trauma presentation for suicide attempts\] and incarcerated patients will be excluded as they may lack autonomy, decision-making capacity and the ability to meet follow-ups.
6. Patients with substance use disorders, due to increased abuse potential and possible baseline hepatic injury.
7. Patients who are on blood thinning medication, at baseline.
8. Patients receiving hormone treatment.
9. Patients with active cancers.
10. Patients with a history of hypercalcemia/parathyroid disease and chronic renal disease.

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Primary outcomes:
measure: Delta volumetric vastus medialis diameter on MRI
timeFrame: upto 6 months
Secondary outcomes:
measure: Delta volumetric thigh muscle mass on MRI
timeFrame: Up to 1 year
measure: Functional measure: 6-minute walk test
timeFrame: Up to 1 year
measure: Activity count by ActiGraph GT3X-BT
timeFrame: Up to 1 year
measure: Short Form 36 Health Survey
timeFrame: Up to 1 year
measure: Patient-Reported Outcomes Measurement Information System (PROMIS)
timeFrame: Up to 1 year
measure: Standard AP and Lateral X-Rays
timeFrame: Through study completion, an average of 1 year
measure: Length of in-patient Acute Hospital stay, and Rehabilitation stay
timeFrame: Through study completion, an average of 1 year
measure: MARX Scale
timeFrame: Up to 1 year
measure: VAS Score
timeFrame: Up to 1 year
measure: Hand-Held Dynamometer
timeFrame: Up to 1 year
Other outcomes:
Locations:
Study officials:
References: