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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03559114
Recruitment Status : Recruiting
First Posted : June 15, 2018
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
Sunnybrook Research Institute
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Dalteparin Drug: Saline Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: PROTEST Trial - PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury, a Double-blind Randomized Controlled Trial
Actual Study Start Date : July 19, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Sodium Chloride




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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).

  3. 180-day Mortality [ Time Frame: 180 days ]
    Mortality at 180 days

  4. 7-day Mortality [ Time Frame: 7 days ]
    Mortality at 7 days

  5. 30-day Mortality [ Time Frame: 30 days ]
    Mortality at 30 days

  6. Delayed VTE after day 7 [ Time Frame: 30 days ]
    Any clinically important VTE occurring between Day 8 to Day 30 detected by treating clinicians

  7. 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.

  8. 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with severe acute TBI defined as GCS ≤8 and within 48 hours of injury ;
  • ≥ 16 years of age (with exception of Quebec where patients will be ≥ 18 years of age)

Exclusion Criteria:

  • Known Hypersensitivity to FRAGMIN (Dalteparin), or its constituents including benzyl alcohol or to other low molecular weight heparins and/or heparins or pork products
  • 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
  • Known septic endocarditis
  • Uncontrollable active bleeding
  • Known major blood clotting disorders
  • Known acute gastroduodenal ulcer (with active bleeding)
  • Severe uncontrolled hypertension (i.e. BP>210 despite medications)
  • Known diabetic or hemorrhagic retinopathy
  • Confirmed complete acute spinal cord injury
  • Unable to receive bilateral SCDs due to femur fracture, below-knee injury requiring external fixation device, critical lower leg ischemia
  • Unstable pelvic fracture requiring external or internal fixation
  • Presence of another confounding factor that can adequately explain the poor GCS at time of presentation (e.g. drug toxicity, seizure).
  • Known presence of irreversible coagulopathies
  • Known Pregnancy
  • Participants extremely low weight (<45 kg), or extremely high weight (>120kg)
  • Not expected to survive more than 48 hours from admission

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03559114


Contacts
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Contact: Farhad Pirouzmand, MD, MSc, FRCSC 416-480-6100 ext 5263 farhad.pirouzmand@sunnybrook.ca
Contact: Catarina Downey, MSc, CCRP 416-480-6100 ext 87546 protest@sunnybrook.ca

Locations
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Canada, Alberta
Foothills Medical Centre Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Stacy Ruddell       Stacy.Ruddell@albertahealthservices.ca   
Principal Investigator: Andreas Kramer, MD         
Royal Alexandra Hospital Not yet recruiting
Edmonton, Alberta, Canada, T5H 3V9
Contact: Patrica Thompson       patrica.thompson@albertahealthservices.ca   
Contact: Tayne Hewer       tayne.hewer@albertahealthservices.ca   
Principal Investigator: Jim Kutsogiannis, MD, MHS, FRCPC         
University of Alberta Hospital Not yet recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Patrica Thompson       patrica.thompson@albertahealthservices.ca   
Contact: Tayne Hewer       tayne.hewer@albertahealthservices.ca   
Principal Investigator: Jim Kutsogiannis, MD, MHS, FRCPC         
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Denise Foster       denise.foster@vch.ca   
Principal Investigator: Donald Griesdale, MD, MPH, FRCPC         
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Contact: Laura-Lee Magennis       Laura.Magennis@nshealth.ca   
Contact: Lisa Julien       lisa.julien@nshealth.ca   
Principal Investigator: Sean Christie, MD, FRCSC         
Sub-Investigator: Laurel Murphy, MD         
Canada, Ontario
Hamilton Health Sciences Centre Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Amanda Martyniuk       martynia@mcmaster.ca   
Principal Investigator: Sunjay Sharma, MD, MSc, FRCSC, FACS         
Sub-Investigator: Paul Engels, MD         
Kingston General Hospital Recruiting
Kingston, Ontario, Canada, K7N 2V7
Contact: Tracy Boyd       Tracy.Boyd@kingstonhsc.ca   
Principal Investigator: Gordon Boyd, MD, PhD, FRCPC         
The Ottawa Hospital Not yet recruiting
Ottawa, Ontario, Canada, KIH 8L6
Contact: Rebecca Porteous       rporteous@ohri.ca   
Contact: Sydney Mietzitis       smiezitis@ohri.ca   
Principal Investigator: Shane English, MD, MSc, FRCPC         
Sunnybrook Health Science Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Principal Investigator: Farhad Pirouzmand, MD, MSc, FRCSC         
Sub-Investigator: Damon Scales, MD, PhD, FRCPC         
Canada, Saskatchewan
Royal University Hospital Recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Contact: Rashmi Nagaraj       rashmi.nagaraj@usask.ca   
Contact: Lilian Urroz       lilian.urroz@usask.ca   
Principal Investigator: Gary Hunter, MD, FRCPC, CSCN (EEG)         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Sunnybrook Research Institute
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: Farhad Pirouzmand, MD, MSc, FRCSC Sunnybrook Health Sciences Centre
Principal Investigator: Damon Scales, MD, PhD, FRCPC Sunnybrook Health Sciences Centre

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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03559114    
Other Study ID Numbers: 0785
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020

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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
Keywords provided by Sunnybrook Health Sciences Centre:
Sequential Compression Device
Anticoagulant Thromboprophylaxis
Deep Vein Thrombosis
Sub Cutaneous
VTE
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Thromboembolism
Venous Thromboembolism
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action