MAGIK for Femoral/Tibial Shaft Fractures (MAGIK)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Femoral Shaft Fracture; Tibial Shaft Fracture
• Intervention / Treatment: Drug: GIK solution; Drug: Isotonic Normal Saline Solution

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Matthew Kingery, MD; Phone Number: 212-598-6000; Email: matthew.kingery@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
      • Contact: Matthew Kingery, MD; Phone Number: 212-598-6000; Email: matthew.kingery@nyulangone.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Femoral shaft fracture or tibial shaft fracture
2. Survival > 72 hours after definitive femur fracture fixation

Exclusion Criteria:

1. Pregnant women as the safety of GIK therapy in pregnant women has not been studied.
2. Age below 18 years
3. Survival < 72 hours after definitive femur fixation.
4. Pathologic fracture
5. Low energy bisphosphonate related atypical fracture
6. Patients with a contraindication to any of the medications on the study list
7. Patients with prior extremity weakness resulting from stroke or other neurological condition
8. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GIK Therapy; 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; Therapy cocktail of Glucose, Insulin and Potassium. The medications will be prepared as per standard protocol. Administered intravenously.
Placebo Comparator: Placebo Control; 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; Placebo injection - administered intravenously.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Sanjit Konda, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Pharmaceutical Solutions
• Other Study ID Numbers: 22-01118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: [matthew.kingery@nyulangone.org]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be given access to the data upon reasonable request. Requests should be directed to matthew.kingery@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No