MAGIK for Femoral/Tibial Shaft Fractures

Study Overview
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Brief Summary
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The purpose of this phase 2 randomized control trial will be to evaluate the effect of glucose-insulin-potassium (GIK) therapy in the setting of lower extremity trauma to reduce short- and long-term muscle damage, acute rhabdomyolysis, and acute kidney injury. The study will consist of 40 patients with femur or tibial shaft fractures randomized to the GIK arm (using a well-described systemic GIK protocol; n = 20) or the control arm (using isotonic saline; n = 20). The use of systemic GIK is expected to decrease the overall amount of lower extremity muscle cell death and result in improved muscle function in the postoperative period. Additionally, the investigators hypothesize that GIK will lead to less severe rhabdomyolysis and a concomitant decrease in the incidence of AKI that results from the byproducts of muscle cell death.

Official Title
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Muscle Trauma, ATP Depletion, and Glucose-Insulin-Potassium Therapy (The MAGIK Trial): A Randomized, Controlled Feasibility Study of GIK Therapy to Decrease Skeletal Muscle Injury in Trauma Patients With Femoral Shaft (OTA 32A-C) and Tibial Shaft (OTA 42A-C) Fractures

Conditions
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Femoral Shaft Fracture, Tibial Shaft Fracture

Intervention / Treatment
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* Drug: GIK solution
* Drug: Isotonic Normal Saline Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Femoral shaft fracture or tibial shaft fracture Survival > 72 hours after definitive femur fracture fixation Exclusion Criteria: Pregnant women as the safety of GIK therapy in pregnant women has not been studied. Age below 18 years Survival < 72 hours after definitive femur fixation. Pathologic fracture Low energy bisphosphonate related atypical fracture Patients with a contraindication to any of the medications on the study list Patients with prior extremity weakness resulting from stroke or other neurological condition Patients with absolute contraindications to undergoing MRI (implanted defibrillator or pacemaker, implanted deep brain stimulator, bullets or gunshot pellets near great vessels or vital organs, cerebral aneurysm clips, cochlear implants, magnetic dental implants).

Ages Eligible for Study
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Minimum 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GIK Therapy<br>In patients randomized to the GIK Therapy Arm, a stepwise GIK infusion process will be performed. Baseline lab values that are markers of skeletal muscle injury (CPK), acute kidney injury (creatinine), and general tissue perfusion (lactate) will be obtained within the first 30 min of arrival to the ED. Subsequently, serial CPK, creatinine, myoglobin and lactate values will be obtained at regularly scheduled intervals until a minimum of 72 hours after definitive fixation or until rhabdomyolysis is resolved and/or kidney function has normalized | Drug: GIK solution<br>* Therapy cocktail of Glucose, Insulin and Potassium. The medications will be prepared as per standard protocol. Administered intravenously.<br>|
| Placebo Comparator: Placebo Control<br>Patients randomized to the control cohort will receive a normal saline infusion instead of GIK. Standard institutional ICU protocol will be used to monitor potassium and glucose levels per current standard-of-care practices and abnormal lab values will be treated accordingly per standard institutional protocols. | Drug: Isotonic Normal Saline Solution<br>* Placebo injection - administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Creatine Kinase (CK) Concentration During Hospital Stay | Measured via standard of care lab assessment. | Up to Day 7 Post-Operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience Acute Kidney Injury (AKI) |  | Up to Week 52 Post-Operation | 
| Number of Participants with Stage 1 AKI |  | Up to Week 52 Post-Operation | 
| Number of Participants with Stage 2 AKI |  | Up to Week 52 Post-Operation | 
| Number of Participants with Stage 3 AKI |  | Up to Week 52 Post-Operation | 
| Patient Reported Outcome Measurement Information System (PROMIS) Physical Function | Measure of self-reported capability rather than actual performance of physical activities. The raw score is the sum of responses and is calculated into a T-score with a mean of 50 and a standard deviation of 10; higher scores indicate greater physical function. | Up to Week 52 Post-Operation | 
| Quadriceps Muscle Strength in the Uninjured Leg | Measured via handheld dynamometer. | Up to Week 52 | 
| Quadriceps Muscle Strength in the Injured Leg | Measured via handheld dynamometer. | Up to Week 52 | 
| Hamstrings Muscle Strength in the Uninjured Leg | Measured via handheld dynamometer. | Up to Week 52 | 
| Hamstrings Muscle Strength in the Injured Leg | Measured via handheld dynamometer. | Up to Week 52 | 
| Uninjured Femur Muscle Volume at Week 4 Post-Op | Muscle volume calculated via MRI. | Week 4 Post-Operation | 
| Injured Femur Muscle Volume at Week 4 Post-Op | Muscle volume calculated via MRI. | Week 4 Post-Operation | 
| Uninjured Femur Muscle Volume at Week 24 Post-Op | Muscle volume calculated via MRI. | Week 24 Post-Operation | 
| Injured Femur Muscle Volume at Week 24 Post-Op | Muscle volume calculated via MRI. | Week 24 Post-Operation | 
| Uninjured Femur Muscle Volume at Week 52 Post-Op | Muscle volume calculated via MRI. | Week 52 Post-Operation | 
| Injured Femur Muscle Volume at Week 52 Post-Op | Muscle volume calculated via MRI. | Week 52 Post-Operation |