Evaluation of the Diagnostic and Therapeutic Value of Tissue Ultrafiltration in Patients at Risk of Acute Compartment Syndrome (ACS)

Study Overview
=================
Brief Summary
-----------------
The study will enroll 200 adults ages 18-60 admitted to the hospital with severe open or closed fractures of the proximal tibia or tibial shaft at risk for ACS. Participants will be randomized to either treatment with tissue ultrafiltration (TUF) catheters (n=100) or to a control group (n=100). All patients will receive continuous pressure monitoring of the anterior compartment of their leg. Both groups will receive comprehensive clinical evaluation and will be treated according to the standard-of-care regarding management of their underlying injury and diagnosis of ACS as practiced by their treating surgeon. In addition, patients randomized to the experimental arm will have three TUF catheters placed in the anterior muscle compartment of the injured limb. The TUF catheters will be connected to a closed suction drain and will remove interstitial fluid from the muscle. All patients will be followed at 6 months following initial hospital discharge. This visit will include a clinical evaluation of complications, hospital admission and emergency room visits, wound and fracture healing, infection, muscle sensory and function exam and patient reported outcome

Detailed Description
-----------------
The study will enroll 200 adults ages 18-60 admitted to the hospital with severe open or closed fractures of the proximal tibia or tibial shaft at risk for ACS. Participants will be randomized to either treatment with tissue ultrafiltration (TUF) catheters (n=100) or to a control group (n=100). All patients will receive continuous pressure monitoring of the anterior compartment of their leg. Both groups will receive comprehensive clinical evaluation and will be treated according to the standard-of-care regarding management of their underlying injury and diagnosis of ACS as practiced by their treating surgeon. In addition, patients randomized to the experimental arm will have three TUF catheters placed in the anterior muscle compartment of the injured limb. The TUF catheters will be connected to a closed suction drain and will remove interstitial fluid from the muscle. All patients will be followed at 6 months following initial hospital discharge. This visit will include a clinical evaluation of complications, hospital admission and emergency room visits, wound and fracture healing, infection, muscle sensory and function exam and patient-reported outcome. The study approach hypothesizes that the expert panel consensus likelihood of ACS, defined as the median of the ratings of the individual panel members who evaluated each patient, the incidence of fasciotomy, and intramuscular pressure (IMP) will be lower in the TUF cohort compared to control. In addition, patients in the TUF cohort will demonstrate superior functional outcome and muscle strength at 6 months following injury compared to those in the control cohort, levels of specific biomarkers as measured in the interstitial fluid will be worse in patients with ACS compared to patients without ACS in the treatment group, and there will be a threshold for each biomarker which is predictive of ACS (biomarkers will be collected from 10 patients enrolled at Hennepin Healthcare only).

Official Title
-----------------
Evaluation of the Diagnostic and Therapeutic Value of Tissue Ultrafiltration in Patients at Risk of Acute Compartment Syndrome (ACS)

Conditions
-----------------
Acute Compartment Syndrome

Intervention / Treatment
-----------------
* Device: Tissue Ultrafiltration Catheters


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The target population for this study include adults ages 18-60 with traumatic severe open or closed fractures of the proximal or tibia shaft at risk for ACS by virtue of their mechanism of injury, fracture pattern, or clinical signs. Recruitment of participants will happen during hospital admission for treatment of injury. To be eligible, patients must enroll in the study within 8 hours of injury and meet all of the following criteria: Patients between the ages of 18 and 60 years Patient can be enrolled in the study and study procedures initiated within 8 hours of injury. Open or closed proximal tibial shaft fracture with displacement, comminution, or segmental pattern; proximal fibula fracture; bicondylar tibial plateau fracture; Schatzker IV medial knee fracture-dislocation; proximal leg injury due to shotgun, rifle, or other projectile. Isolated injury meeting above criteria, except for minor distal extremity injuries (defined as closed injuries distal to wrist and ankle in opposite leg or arms). Patient (or authorized legal representative) willing to sign informed consent. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Patients not willing to participate Patients with non-traumatic cases of acute compartment syndrome (e.g. severe exertion, snakebite, high-pressure injection injury) Patients diagnosed with ACS or impending ACS such that immediate fasciotomy is recommended Soft tissue wounds, including lacerations or abrasions, that are in a location that will interfere with safe insertion of indwelling pressure or TUF catheters (anterior - anterolateral aspect of the leg) Patients not likely to follow-up (are homeless, incarcerated, live out-of-state). Patients with known peripheral vascular disease Non-ambulatory due to an associated complete spinal cord injury; Non-ambulatory before the injury due to a pre-existing condition. Very low clinical concern for ACS at time of admission

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Pressure Monitoring Group<br>Participants in this group will have pressure monitoring of the anterior compartment of their leg using an indwelling IMP catheter (MY01, MY01 Inc., Montreal, CA). The participants will be treated according to the standard-of-care regarding management of their underlying injury and diagnosis of ACS as practiced by their treating surgeon. Participants will be followed for six months post-injury. | |
| Experimental: Tissue Ultrafiltration Intervention Group (TUF)<br>Participants in this group will have pressure monitoring of the anterior compartment of their leg using an indwelling IMP catheter (MY01, MY01 Inc., Montreal, CA). The participants will be treated according to the standard-of-care regarding management of their underlying injury and diagnosis of ACS as practiced by their treating surgeon. In addition, participants in this group will will undergo three TUF of the anterior compartment of the injured limb. Participants will be followed for six months post-injury. | Device: Tissue Ultrafiltration Catheters<br>* patients randomized to the experimental arm will have three TUF catheters placed in the anterior muscle compartment of the injured limb. The TUF catheters will be connected to a closed suction drain and will remove interstitial fluid from the muscle.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To test whether there are differences in the incidence of ACS in patients with severe leg injuries treated with active TUF compared to the control group. | The consensus likelihood of ACS as assessed by a panel of experts after review of a standardized patient profile. | 6 months post injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To test whether TUF reduces the incidence of fasciotomy compared to control patients. | Proportion of patients with a of fasciotomy | 6 months post injury | 
| To test whether TUF reduces Intramuscular Pressure (IMP) compared to control patients. | Proportion of patients with a of Change in continuously measured IMP. | 6 months post injury | 
| To test the impact of TUF on improving patient global health | PROMIS Global Health | 6 months post injury | 
| To test the impact of TUF on improving patient physical function | PROMIS Physical Function | 6 months post injury |