Biomarkers in the Diagnosis of Acute Compartment Syndrome (BioFACTS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Compartment Syndrome; Tibia Fracture
• Intervention / Treatment: Other: Blood samples and biopsies

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.

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

• Study Contact: Name: Jörg Schilcher, MD, PhD; Phone Number: +46101030000; Email: jorg.schilcher@liu.se
• Study Contact Backup: Name: Abraham Nilsson, MD; Phone Number: +46101030000; Email: abraham.nilsson@regionostergotland.se

Study Locations

• Sweden
  • Linkoping, Sweden, 581 85
    • Recruiting
    • University Hospital of Linkoping
    • Contact: Jörg Schilcher, MD, PhD; Phone Number: +46101030000; Email: jorg.schilcher@liu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a traumatic tibial fracture with or without other concomitant fractures and patients with suspected acute compartment syndrome. The study population is sampled in a consecutive way.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tibial fracture; Patients with a traumatic tibial fracture and without acute compartment syndrome.	Other: Blood samples and biopsies; Blood samples for analysis of biomarkers of muscle damage. Muscle biopsies for histological analysis of muscle damage.
Tibial fracture complicated by acute compartment syndrome; Patients with a tibial fracture and acute compartment syndrome of fractured leg.	Other: Blood samples and biopsies; Blood samples for analysis of biomarkers of muscle damage. Muscle biopsies for histological analysis of muscle damage.
Acute compartment syndrome without fracture; Patients with acute compartment syndrome but without a fracture.	Other: Blood samples and biopsies; Blood samples for analysis of biomarkers of muscle damage. Muscle biopsies for histological analysis of muscle damage.

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

Collaborators and Investigators

• Sponsor: University Hospital, Linkoeping
• Collaborators: Helsinki University Central Hospital; Medical Research Council of Southeast Sweden
• Investigators: Principal Investigator: Jörg Schilcher, PhD, University Hospital, Linkoeping

Publications and helpful links

General Publications

• Nilsson A, Ibounig T, Lyth J, Alkner B, von Walden F, Fornander L, Ramo L, Schmidt A, Schilcher J. BioFACTS: biomarkers of rhabdomyolysis in the diagnosis of acute compartment syndrome - protocol for a prospective multinational, multicentre study involving patients with tibial fractures. BMJ Open. 2022 May 2;12(5):e059918. doi: 10.1136/bmjopen-2021-059918.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 5, 2018
• Primary Completion (ANTICIPATED): June 1, 2023
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: December 13, 2020
• First Submitted That Met QC Criteria: December 13, 2020
• First Posted (ACTUAL): December 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Fractures, Bone; Wounds and Injuries; Leg Injuries; Disease; Musculoskeletal Diseases; Muscular Diseases; Syndrome; Tibial Fractures; Compartment Syndromes
• Other Study ID Numbers: BioFACTS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No