PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury (PROTEST) (PROTEST)
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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 |
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Recruitment Status :
Recruiting
First Posted : June 15, 2018
Last Update Posted : June 15, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Traumatic Brain Injury | Drug: Dalteparin Drug: Saline | Phase 3 |
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 (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 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Anticoagulant
Dalteparin sodium (at a dose of 5000 IU once daily by subcutaneous injection) for 7 days upon randomization after hospital admission.
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Drug: Dalteparin
Dalteparin in prophylactic doses administered daily if screening criteria are satisfied.
Other Name: Fragmin |
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Placebo Comparator: Saline
Saline (0.2 mL) once daily by subcutaneous injection for 7 days upon randomization after hospital admission.
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Drug: Saline
Saline in prophylactic doses administered daily if screening criteria are satisfied.
Other Name: Sodium Chloride |
- Clinically important VTE [ Time Frame: 8 days ]
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
- 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
- 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).
- 180-day Mortality [ Time Frame: 180 days ]Mortality at 180 days
- 7-day Mortality [ Time Frame: 7 days ]Mortality at 7 days
- 30-day Mortality [ Time Frame: 30 days ]Mortality at 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
- 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.
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 and moderate acute TBI defined as:
- GCS of ≤8 or
- GCS of 9-12 (moderate) with any intracranial hemorrhage seen on CT scan (patients with only subarachnoid hemorrhage are excluded)
ii) Upon randomization patient can receive the first dose of study drug in the first 3 calendar days of the time of injury
ii) ≥ 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
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
| 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 |
| Canada, Alberta | |
| Foothills Medical Centre | Recruiting |
| Calgary, Alberta, Canada, T2N 2T9 | |
| Contact: Shaleen Maharaj Shaleen.Maharaj@albertahealthservices.ca | |
| Principal Investigator: Andreas Kramer, MD | |
| Royal Alexandra Hospital | 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 | 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: Rebecca Grey Rebecca.Grey@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 | 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: Emily Junk emily.junk@usask.ca | |
| Principal Investigator: Gary Hunter, MD, FRCPC, CSCN (EEG) | |
| Principal Investigator: | Farhad Pirouzmand, MD, MSc, FRCSC | Sunnybrook Health Sciences Centre | |
| Principal Investigator: | Damon Scales, MD, PhD, FRCPC | Sunnybrook Health Sciences Centre |
| 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: | June 15, 2021 |
| Last Verified: | June 2021 |
| 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 |
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Sequential Compression Device Anticoagulant Thromboprophylaxis Deep Vein Thrombosis Sub Cutaneous VTE |
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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 Tinzaparin Heparin, Low-Molecular-Weight Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |