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

Traumatic Brain Injury Clinical Trial

— PROTEST  

Official title:

PROTEST Trial - PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury, a Double-blind Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03559114
• Other study ID #: 0785
• Status: Recruiting
• Phase: Phase 3
• Start date: July 19, 2018
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Sunnybrook Health Sciences Centre
• Contact: Farhad Pirouzmand, MD, MSc, FRCSC
• Phone: 416-480-6100
• Email: farhad.pirouzmand[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

The pragmatic nature of this study seeks to include all consecutive patients presenting with significant TBI, regardless of whether ICB is evident at presentation. Inclusion criteria are the following:

i) Patients with severe TBI defined as GCS of =8, or

ii) Patients with moderate TBI defined as GCS = 9-12, admitted to ICU, with at least some ICB present on initial CT scan and any of the following:

1. Requiring invasive mechanical ventilation at the time of screening

2. Increased ICB on repeat CT scan compared to initial CT scan

iii) Upon randomization the patient will be able to receive the first dose of study drug in the first 3 calendar days from the time of injury

iv) = 18 years of age

Exclusion Criteria

All participants meeting any of the following exclusion criteria at baseline will be excluded from participation in this study:

i) Known Hypersensitivity to FRAGMIN (Dalteparin), or its constituents including benzyl alcohol or to other low molecular weight heparins and/or heparins or pork products

ii) Known history of confirmed or suspected immunologically-mediated heparin-induced thrombocytopenia (delayed-onset severe thrombocytopenia), and/or in patients with a known history of a positive in vitro platelet-aggregation test in the presence of FRAGMIN (Dalteparin) is positive

iii) Known septic endocarditis

iv) Uncontrollable active bleeding

v) Known major blood clotting disorders

vi) Known acute gastroduodenal ulcer (with active bleeding)

vii) Severe uncontrolled hypertension (i.e. BP>210 despite medications)

viii) Known diabetic or hemorrhagic retinopathy

ix) Anticipated to be unable to receive SCD on at least one lower extremity due to nature of injuries for duration of intervention period

x) Presence of another confounding factor that can adequately explain the poor GCS at time of presentation (e.g. drug toxicity, seizure)

xi) Known presence of irreversible coagulopathies

xii) Known Pregnancy

xiii) Participants extremely low weight (<45 kg), or extremely high weight (>120kg)

xiv) Not expected to survive more than 48 hours from admission

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Thromboembolism
• Traumatic Brain Injury
• Venous Thromboembolism
• Wounds and Injuries

Intervention

Drug:
• Dalteparin
Dalteparin in prophylactic doses administered daily if screening criteria are satisfied.
• Saline
Saline in prophylactic doses administered daily if screening criteria are satisfied.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
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	Hopital de L'Enfant-Jesus	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Canada	Unity Health Toronto	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Canadian Institutes of Health Research (CIHR), Sunnybrook Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinically important VTE	Composite outcome of clinically-important VTE within 7±1 days after randomization defined as any of: Symptomatic, objectively-confirmed pulmonary embolism (PE), or; Symptomatic, objectively-confirmed, proximal leg deep vein thrombosis (DVT), or; Proximal (above knee) leg DVT on compression ultrasonography on Day 7±1	8 days
Secondary	Clinically-important ICB (Intracranial bleeding) progression	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	7 days
Secondary	Objectively confirmed new or progressing ICB on radiology,	Assessed by comparing the initial brain CT (Day 0) to that performed within 8±1 days following randomization (or most recent prior to death).	8 days
Secondary	180-day Mortality	Mortality at 180 days	180 days
Secondary	7-day Mortality	Mortality at 7 days	7 days
Secondary	30-day Mortality	Mortality at 30 days	30 days
Secondary	Delayed VTE after day 7	Any clinically important VTE occurring between Day 8 to Day 30 detected by treating clinicians	30 days
Secondary	Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended	Glasgow Outcome Scale Extended (GOSE) at Day 30±5 by phone interview.	30 days
Secondary	Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended	Glasgow Outcome Scale Extended (GOSE) at Day 180±14 by phone interview.	180 days
Secondary	Quality of life outcome at 30 days as measured by the EuroQol5D	EQ-5D (EuroQol 5D) at Day 30±5 by phone interview.	30 days
Secondary	Quality of life outcome at 180 days as measured by the EuroQol5D	EQ-5D (EuroQol 5D) at Day 180±14 by phone interview.	180 days