Traumatic Brain InjuryPhase 3PROTESTNCT03559114
PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury (PROTEST)
A Phase 3 study testing Dalteparin and Saline in people with Traumatic Brain Injury, run by Sunnybrook Health Sciences Centre at 12 sites in Canada.
Trial summary
This is a phase III, multi-centre, double blind, randomized controlled trial of patients with traumatic brain injury (TBI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Dalteparin and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,100 participants
- Where
- 12 sitesCanada
- Study dates
- 19 Jul 2018to Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Patients with severe TBI defined as GCS of ≤8, or
- 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:
- Requiring invasive mechanical ventilation at the time of screening
- Increased ICB on repeat CT scan compared to initial CT scan
- 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
- ≥ 18 years of age
Who cannot join
- All participants meeting any of the following exclusion criteria at baseline will be excluded from participation in this study:
- 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
Show all 15Show fewer
- Known acute gastroduodenal ulcer (with active bleeding)
- Severe uncontrolled hypertension (i.e. BP>210 despite medications)
- Known diabetic or hemorrhagic retinopathy
- Anticipated to be unable to receive SCD on at least one lower extremity due to nature of injuries for duration of intervention period
- 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
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Canada12 sites, 12 recruiting
- Recruiting
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
Olesya Dmitrieva, olesya.dmitrieva@ucalgary.ca
Andreas Kramer, MD
- Recruiting
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
Patrica Thompson, patrica.thompson@albertahealthservices.ca
Tayne Hewer, tayne.hewer@albertahealthservices.ca
- Recruiting
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Patrica Thompson, patrica.thompson@albertahealthservices.ca
Tayne Hewer, tayne.hewer@albertahealthservices.ca
- Recruiting
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 3A7
Laura-Lee Magennis, Laura.Magennis@nshealth.ca
Lisa Julien, lisa.julien@nshealth.ca
- Recruiting
Hamilton Health Sciences Centre
Hamilton, Ontario, L8N 3Z5
Amanda Martyniuk, martynia@mcmaster.ca
Sunjay Sharma, MD, MSc, FRCSC, FACS
- Recruiting
Kingston General Hospital
Kingston, Ontario, K7N 2V7
Tracy Boyd, Tracy.Boyd@kingstonhsc.ca
Gordon Boyd, MD, PhD, FRCPC
- Recruiting
The Ottawa Hospital
Ottawa, Ontario, KIH 8L6
Rebecca Porteous, rporteous@ohri.ca
Sydney Mietzitis, smiezitis@ohri.ca
- Recruiting
Hopital de L'Enfant-Jesus
Québec, Quebec, G1J 1Z4
David Bellemare, David.Bellemare@crchudequebec.ulaval.ca
Alexis Turgeon-Fournier, MD
- Recruiting
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
Emily Junk, emily.junk@usask.ca
Gary Hunter, MD, FRCPC, CSCN (EEG)
- Recruiting
Sunnybrook Health Science Centre
Toronto, Ontario, M4N 3M5
Farhad Pirouzmand, MD, MSc, FRCSC
Damon Scales, MD, PhD, FRCPC
- Recruiting
Unity Health Toronto
Toronto, Ontario, M5B1W8
Marlene Santos, MD, MSc, Marlene.Santos@unityhealth.to
Michael Cusimano, MD, MHPE, FRCS, PhD
- Recruiting
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Rebecca Grey, Rebecca.Grey@vch.ca
Donald Griesdale, MD, MPH, FRCPC
About this study
Official title: PROTEST Trial - PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury, a Double-blind Randomized Controlled Trial
This is a phase III, multi-centre, double blind, randomized controlled trial of patients with traumatic brain injury (TBI).
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Dalteparin, Saline
- Keywords
- Sequential Compression Device, Anticoagulant Thromboprophylaxis, Deep Vein Thrombosis, Sub Cutaneous, VTE
- Medical subject headings
- Brain Injuries, Traumatic, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DalteparinDrug
Also called Fragmin
Dalteparin in prophylactic doses administered daily if screening criteria are satisfied.
SalineDrug
Also called Sodium Chloride
Saline in prophylactic doses administered daily if screening criteria are satisfied.
| Study group | Role | What they receive |
|---|---|---|
| Anticoagulant | Active comparator | Dalteparin sodium (at a dose of 5000 IU once daily by subcutaneous injection) for 7 days upon randomization after hospital admission. Receives: Drug: Dalteparin |
| Saline | Placebo comparator | Saline (0.2 mL) once daily by subcutaneous injection for 7 days upon randomization after hospital admission. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 8 days
Secondary outcomes (10)
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
Measured: 7 days
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).
Measured: 8 days
180-day Mortality
Mortality at 180 days
Measured: 180 days
7-day Mortality
Mortality at 7 days
Measured: 7 days
30-day Mortality
Mortality at 30 days
Measured: 30 days
Delayed VTE after day 7
Any clinically important VTE occurring between Day 8 to Day 30 detected by treating clinicians
Measured: 30 days
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.
Measured: 30 days
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.
Measured: 180 days
Quality of life outcome at 30 days as measured by the EuroQol5D
EQ-5D (EuroQol 5D) at Day 30±5 by phone interview.
Measured: 30 days
Quality of life outcome at 180 days as measured by the EuroQol5D
EQ-5D (EuroQol 5D) at Day 180±14 by phone interview.
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start19 Jul 2018
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Research Institute
- Responsible party
- Sponsor
- Investigators
- Farhad Pirouzmand, MD, MSc, FRCSC, Principal investigator, Sunnybrook Health Sciences CentreDamon Scales, MD, PhD, FRCPC, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03559114
- Sponsor's protocol ID
- 0785
- Acronym
- PROTEST
- Status last verified
- May 2024
- First submitted
- 10 Apr 2018
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pirouzmand F, Mathieu F, Mansouri A, Kavikondala K, Alkins R, Boyd JG, Christie S, Couillard P, Cusimano MD, Engels PT, English S, Fourney D, Fowler R, Geerts W, Gooderham PA, Griesdale D, Hunter G, Jabehdar Maralani P, Kelly ME, Klein G, Kramer AH, Kromm J, Kutsogiannis DJ, Lauzier F, Machnowska M, Maslove DM, Mejia-Mantilla J, Midha R, Misra B, Murphy L, O'Kelly CJ, Patel C, Pinto RL, Pronovost AP, Sekhon M, Sharma SV, Sinclair J, Tsai E, Turgeon AF, Warade A, Scales DC; PROTEST investigators. Prophylaxis for venous thromboembolism in traumatic brain injury: protocol for a randomised controlled trial. BMJ Open. 2025 Dec 25;15(12):e114158. doi: 10.1136/bmjopen-2025-114158.
PubMed 41453781
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PROTEST Trial - PROphylaxis for Venous ThromboEmbolism in Severe Traumatic Brain Injury, a Double-blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03559114
- Acronym / sponsor ID
- PROTEST / 0785
- Conditions
- Traumatic Brain Injury
- Keywords
- Sequential Compression Device, Anticoagulant Thromboprophylaxis, Deep Vein Thrombosis, Sub Cutaneous, VTE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,100 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Sunnybrook Research Institute
- Study start
- 19 Jul 2018 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 15 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anticoagulant | Active comparator | Drug: DalteparinDalteparin sodium (at a dose of 5000 IU once daily by subcutaneous injection) for 7 days upon randomization after hospital admission. |
| Saline | Placebo comparator | Drug: SalineSaline (0.2 mL) once daily by subcutaneous injection for 7 days upon randomization after hospital admission. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- Patients with severe TBI defined as GCS of ≤8, or
- 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:
- Requiring invasive mechanical ventilation at the time of screening
- Increased ICB on repeat CT scan compared to initial CT scan
Key exclusion criteria (15 listed)
- All participants meeting any of the following exclusion criteria at baseline will be excluded from participation in this study:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DalteparinAlso: FragminDalteparin in prophylactic doses administered daily if screening criteria are satisfied. | Drug | Anticoagulant |
| SalineAlso: Sodium ChlorideSaline in prophylactic doses administered daily if screening criteria are satisfied. | Drug | Saline |
Primary outcome
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
10 secondary outcomes
Clinically-important ICB (Intracranial bleeding) progression
Time frame: 7 days
Objectively confirmed new or progressing ICB on radiology,
Time frame: 8 days
180-day Mortality
Time frame: 180 days
7-day Mortality
Time frame: 7 days
30-day Mortality
Time frame: 30 days
Delayed VTE after day 7
Time frame: 30 days
Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended
Time frame: 30 days
Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended
Time frame: 180 days
Quality of life outcome at 30 days as measured by the EuroQol5D
Time frame: 30 days
Quality of life outcome at 180 days as measured by the EuroQol5D
Time frame: 180 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 41453781Pirouzmand F, Mathieu F, Mansouri A, Kavikondala K, Alkins R, Boyd JG, Christie S, Couillard P, Cusimano MD, Engels PT, English S, Fourney D, Fowler R, Geerts W, Gooderham PA, Griesdale D, Hunter G, Jabehdar Maralani P, Kelly ME, Klein G, Kramer AH, Kromm J, Kutsogiannis DJ, Lauzier F, Machnowska M, Maslove DM, Mejia-Mantilla J, Midha R, Misra B, Murphy L, O'Kelly CJ, Patel C, Pinto RL, Pronovost AP, Sekhon M, Sharma SV, Sinclair J, Tsai E, Turgeon AF, Warade A, Scales DC; PROTEST investigators. Prophylaxis for venous thromboembolism in traumatic brain injury: protocol for a randomised controlled trial. BMJ Open. 2025 Dec 25;15(12):e114158. doi: 10.1136/bmjopen-2025-114158.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Farhad Pirouzmand, MD, MSc, FRCSC principal investigator
Sunnybrook Health Sciences Centre
Damon Scales, MD, PhD, FRCPC principal investigator
Sunnybrook Health Sciences Centre
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dalteparin and Saline in people with Traumatic Brain Injury, run by Sunnybrook Health Sciences Centre at 12 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Farhad Pirouzmand, MD, MSc, FRCSC (416-480-6100 ext. 5263, farhad.pirouzmand@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically important VTE (time frame: 8 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03559114, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024; AzTrials last refreshed its copy on 7 Nov 2026.