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

November 16, 2022 updated by: Sunnybrook Health Sciences Centre

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

1100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Recruiting
        • Vancouver General Hospital
        • Principal Investigator:
          • Donald Griesdale, MD, MPH, FRCPC
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3A7
        • Recruiting
        • Queen Elizabeth II Health Sciences Centre
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sean Christie, MD, FRCSC
        • Sub-Investigator:
          • Laurel Murphy, MD
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Recruiting
        • Hamilton Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Sunjay Sharma, MD, MSc, FRCSC, FACS
        • Sub-Investigator:
          • Paul Engels, MD
      • Kingston, Ontario, Canada, K7N 2V7
        • Recruiting
        • Kingston General Hospital
        • Principal Investigator:
          • Gordon Boyd, MD, PhD, FRCPC
      • Ottawa, Ontario, Canada, KIH 8L6
        • Recruiting
        • The Ottawa Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Shane English, MD, MSc, FRCPC
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Health Science Centre
        • Principal Investigator:
          • Farhad Pirouzmand, MD, MSc, FRCSC
        • Sub-Investigator:
          • Damon Scales, MD, PhD, FRCPC
      • Toronto, Ontario, Canada, M5B1W8
        • Recruiting
        • Unity Health Toronto
        • Contact:
        • Principal Investigator:
          • Michael Cusimano, MD, MHPE, FRCS, PhD
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Recruiting
        • Royal University Hospital
        • Contact:
        • Principal Investigator:
          • Gary Hunter, MD, FRCPC, CSCN (EEG)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Anticoagulant
Dalteparin sodium (at a dose of 5000 IU once daily by subcutaneous injection) for 7 days upon randomization after hospital admission.
Drug: Dalteparin
Dalteparin in prophylactic doses administered daily if screening criteria are satisfied.
Other Names:
  • Fragmin
PLACEBO_COMPARATOR: Saline
Saline (0.2 mL) once daily by subcutaneous injection for 7 days upon randomization after hospital admission.
Drug: Saline
Saline in prophylactic doses administered daily if screening criteria are satisfied.
Other Names:
  • Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinically important VTE
Time Frame: 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
8 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinically-important ICB (Intracranial bleeding) progression
Time Frame: 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
7 days
Objectively confirmed new or progressing ICB on radiology,
Time Frame: 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).
8 days
180-day Mortality
Time Frame: 180 days
Mortality at 180 days
180 days
7-day Mortality
Time Frame: 7 days
Mortality at 7 days
7 days
30-day Mortality
Time Frame: 30 days
Mortality at 30 days
30 days
Delayed VTE after day 7
Time Frame: 30 days
Any clinically important VTE occurring between Day 8 to Day 30 detected by treating clinicians
30 days
Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended
Time Frame: 30 days
Glasgow Outcome Scale Extended (GOSE) at Day 30±5 by phone interview.
30 days
Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended
Time Frame: 180 days
Glasgow Outcome Scale Extended (GOSE) at Day 180±14 by phone interview.
180 days
Quality of life outcome at 30 days as measured by the EuroQol5D
Time Frame: 30 days
EQ-5D (EuroQol 5D) at Day 30±5 by phone interview.
30 days
Quality of life outcome at 180 days as measured by the EuroQol5D
Time Frame: 180 days
EQ-5D (EuroQol 5D) at Day 180±14 by phone interview.
180 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Canadian Institutes of Health Research (CIHR)
Sunnybrook Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 19, 2018

Primary Completion (ANTICIPATED)

December 1, 2026

Study Completion (ANTICIPATED)

December 1, 2027

Study Registration Dates

First Submitted

April 10, 2018

First Submitted That Met QC Criteria

June 14, 2018

First Posted (ACTUAL)

June 15, 2018

Study Record Updates

Last Update Posted (ACTUAL)

November 17, 2022

Last Update Submitted That Met QC Criteria

November 16, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0785

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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