Biomarkers in the Diagnosis of Acute Compartment Syndrome

Study Overview
=================
Brief Summary
-----------------
This prospective multinational, multicentre cohort study aims to investigate the hypothesis that biomarkers of muscle cell damage can predict acute compartment syndrome in patients with tibial fractures.

Detailed Description
-----------------
Patients with a tibial fracture are included. P-myoglobin and P-creatine phosphokinase are analysed at 6-hourly intervals pre- and if applicable, postoperatively after surgical fixation or fasciotomy. Also, blood samples will be collected in 6 hourly intervals if acute compartment syndrome is suspected. An expert panel of senior orthopaedic surgeons will retrospectively assess study data and classify patients who had undergone fasciotomy into those with and without acute compartment syndrome. Blood samples will also be collected in patients with acute compartment syndrome without tibial fractures, to serve as a positive control group.

Official Title
-----------------
Biomarkers of Rhabdomyolysis in the Diagnosis of Acute Compartment Syndrome: Study Protocol of a Prospective Multinational, Multicentre Study in Patients With Tibial Fractures.

Conditions
-----------------
Tibia Fracture, Acute Compartment Syndrome

Intervention / Treatment
-----------------
* Other: Blood samples and biopsies


Participation Criteria
=================
Eligibility Criteria
-----------------
Tibial fracture group Inclusion Criteria: - Traumatic tibial fracture Exclusion Criteria: Malignancy Acute myocardial infarction Kidney failure (GFR ≤35 ml/min) Muscle disease Paraplegia/tetraplegia Non-fracture group Inclusion Criteria: - Suspected acute compartment syndrome Exclusion Criteria: Malignancy Acute myocardial infarction Kidney failure (GFR ≤35 ml/min) Muscle disease Paraplegia/tetraplegia Associated fracture Acute vascular event

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 65 Years

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tibial fracture<br>Patients with a traumatic tibial fracture and without acute compartment syndrome. | Other: Blood samples and biopsies<br>* Blood samples for analysis of biomarkers of muscle damage. Muscle biopsies for histological analysis of muscle damage.<br>|
| Tibial fracture complicated by acute compartment syndrome<br>Patients with a tibial fracture and acute compartment syndrome of fractured leg. | Other: Blood samples and biopsies<br>* Blood samples for analysis of biomarkers of muscle damage. Muscle biopsies for histological analysis of muscle damage.<br>|
| Acute compartment syndrome without fracture<br>Patients with acute compartment syndrome but without a fracture. | Other: Blood samples and biopsies<br>* Blood samples for analysis of biomarkers of muscle damage. Muscle biopsies for histological analysis of muscle damage.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak levels of P-myoglobin and P-creatine phosphokinase | A series of blood samples will be collected with 6-hourly interval at the following time-points: Admission to hospital: P-myoglobin and P-creatine phosphokinase are collected at 6-hourly intervals for a maximum of 48 hours or until definitive surgical fixation of the fracture is performed (temporary external fixation excluded). Surgical fracture treatment: After surgical intervention (definitive surgical fracture treatment, excluding temporary external fixation), another series of blood samples is collected with 6-hourly interval for 24 hours. Acute compartment syndrome: If suspicion of acute compartment syndrome emerges, blood samples will be collected with 6-hourly interval until fasciotomy is performed or the suspicion is written off. After fasciotomy, blood samples will be continued with 6-hourly interval for 24 hours. | Up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MicroRNA | We also collect microRNA specific for muscle damage at the same time intervals and use it as an objective measures of muscle damage. | Up to 5 days | 
| Histological evidence of muscle damage | At surgery (internal fixation or fasciotomy) biopsies are taken from tibialis anterior muscle in some centres for further histological analysis. Two biopsies are taken from the fractured leg, one near the fracture and one at distance, and one biopsy from the uninjured leg (control). Biopsies are frozen within 30 minutes using liquid nitrogen and isopentane and stored in minus 80 degrees Celsius. | At internal fixation and/or fasciotomy |