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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Dalteparin
  Dalteparin in prophylactic doses administered daily if screening criteria are satisfied.
• Препарат Saline
  Saline in prophylactic doses administered daily if screening criteria are satisfied.

Первичные конечные точки

• Clinically important VTE [Срок оценки: 8 days]

Вторичные конечные точки (10)

• Clinically-important ICB (Intracranial bleeding) progression [Срок оценки: 7 days]
• Objectively confirmed new or progressing ICB on radiology, [Срок оценки: 8 days]
• 180-day Mortality [Срок оценки: 180 days]
• 7-day Mortality [Срок оценки: 7 days]
• 30-day Mortality [Срок оценки: 30 days]
• Delayed VTE after day 7 [Срок оценки: 30 days]
• Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended [Срок оценки: 30 days]
• Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended [Срок оценки: 180 days]
• Quality of life outcome at 30 days as measured by the EuroQol5D [Срок оценки: 30 days]
• Quality of life outcome at 180 days as measured by the EuroQol5D [Срок оценки: 180 days]

Критерии участия

Критерии включения

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:

• Requiring invasive mechanical ventilation at the time of screening
• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Канада · 12 центров

• Foothills Medical Centre — Calgary
• Royal Alexandra Hospital — Edmonton
• University of Alberta Hospital — Edmonton
• Vancouver General Hospital — Vancouver
• Queen Elizabeth II Health Sciences Centre — Halifax
• Hamilton Health Sciences Centre — Hamilton
• Kingston General Hospital — Kingston
• The Ottawa Hospital — Ottawa
• … и ещё 4 центра

Публикации

• 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 PMID 41453781

Идентификаторы

NCT: NCT03559114 · 0785

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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