PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury (PROTEST)

Phase 3

Recruiting

• Conditions: Traumatic Brain Injury
• Interventions: Drug: Saline; Drug: Dalteparin

• Registration Number: NCT03559114
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

This is a pilot study, phase III, multi-centre, double blind, randomized controlled trial of patients with traumatic brain injury (TBI).

Detailed Description

Patients with severe brain injury are at risk for developing blood clots in their legs, which can travel to the lungs. This potentially serious complication is known as venous thromboembolism (VTE). Anticoagulants are commonly used to prevent VTE in hospital patients. However, in patients with major head injury, anticoagulant prevention is commonly delayed for the fear that it can potentially lead to further bleeding in the brain. Another method that aims to prevent blood clots involves the use of sequential compression device (SCD) that compress the legs and increase the flow of blood in the leg veins.

This study will compare results from patients who receive the SCDs only to those who receive both SCD and anticoagulants. The outcome of this study will provide information about how best to prevent blood clots while not increase brain bleeding after head injury.

Study Timeline

• Study First Submitted: 2018-04-10
• Study First Submitted QC: 2018-06-14
• Study First Posted: 2018-06-15
• Study Start: 2018-07-19
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-10
• Last Update Posted: 2024-05-13
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1100

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline	Saline	Saline (0.2 mL) once daily by subcutaneous injection for 7 days upon randomization after hospital admission.
Anticoagulant	Dalteparin	Dalteparin sodium (at a dose of 5000 IU once daily by subcutaneous injection) for 7 days upon randomization after hospital admission.

Primary Outcome Measures

Name	Time	Method
Clinically important VTE	8 days	Composite outcome of clinically-important VTE within 7±1 days after randomization defined as any of: 1. Symptomatic, objectively-confirmed pulmonary embolism (PE), or; 2. Symptomatic, objectively-confirmed, proximal leg deep vein thrombosis (DVT), or; 3. Proximal (above knee) leg DVT on compression ultrasonography on Day 7±1

Secondary Outcome Measures

Name	Time	Method
180-day Mortality	180 days	Mortality at 180 days
Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended	30 days	Glasgow Outcome Scale Extended (GOSE) at Day 30±5 by phone interview.
Clinically-important ICB (Intracranial bleeding) progression	7 days	Clinically-important ICB progression within 7±1 days after randomization , as defined by having (1) any increase in volume of blood in the brain on any CT scan within 7±1 days relative to initial CT scan on Day 0\* AND (2) clinical worsening within 24 hours of this CT scan, defined by one or more of the following: * Surgical intervention related to increased ICB after Day 0 (craniotomy/craniectomy, ICP monitor, external ventricular drain); * Decrease of GCS (Glasgow Coma Scale) by at least 2 points not related to sedation; * Increase in ICP \>5 mmHg on 2 occasions at least 6 hours apart despite medical therapy (if ICP monitor is in place); * Death
Objectively confirmed new or progressing ICB on radiology,	8 days	Assessed by comparing the initial brain CT (Day 0) to that performed within 8±1 days following randomization (or most recent prior to death).
Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended	180 days	Glasgow Outcome Scale Extended (GOSE) at Day 180±14 by phone interview.
Quality of life outcome at 180 days as measured by the EuroQol5D	180 days	EQ-5D (EuroQol 5D) at Day 180±14 by phone interview.
7-day Mortality	7 days	Mortality at 7 days
Quality of life outcome at 30 days as measured by the EuroQol5D	30 days	EQ-5D (EuroQol 5D) at Day 30±5 by phone interview.
30-day Mortality	30 days	Mortality at 30 days
Delayed VTE after day 7	30 days	Any clinically important VTE occurring between Day 8 to Day 30 detected by treating clinicians

Trial Locations

Locations (12)

Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

Royal Alexandra Hospital; 🇨🇦 Edmonton, Alberta, Canada

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Queen Elizabeth II Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Hamilton Health Sciences Centre; 🇨🇦 Hamilton, Ontario, Canada

Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

Unity Health Toronto; 🇨🇦 Toronto, Ontario, Canada

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada

Hopital de L'Enfant-Jesus; 🇨🇦 Quebec, Canada