Clinical trial NCT03559114: PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury (PROTEST)
Official title: PROTEST Trial - PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury, a Double-blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Traumatic Brain Injury
Keywords: Sequential Compression Device
Anticoagulant Thromboprophylaxis
Deep Vein Thrombosis
Sub Cutaneous
VTE
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
First posted: 2018-06-15
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinically important VTE
timeFrame: 8 days
Secondary outcomes:
measure: Clinically-important ICB (Intracranial bleeding) progression
timeFrame: 7 days
measure: Objectively confirmed new or progressing ICB on radiology,
timeFrame: 8 days
measure: 180-day Mortality
timeFrame: 180 days
measure: 7-day Mortality
timeFrame: 7 days
measure: 30-day Mortality
timeFrame: 30 days
measure: Delayed VTE after day 7
timeFrame: 30 days
measure: Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended
timeFrame: 30 days
measure: Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended
timeFrame: 180 days
measure: Quality of life outcome at 30 days as measured by the EuroQol5D
timeFrame: 30 days
measure: Quality of life outcome at 180 days as measured by the EuroQol5D
timeFrame: 180 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto
state: Ontario
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Quebec
country: Canada
facility: Hopital de L'Enfant-Jesus
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Farhad Pirouzmand, MD, MSc, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Damon Scales, MD, PhD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: