PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
- Conditions
- Critical IllnessDeep Venous Thrombosis
- Interventions
- Drug: LMWH (Fragmin, dalteparin)
- Registration Number
- NCT00182143
- Lead Sponsor
- McMaster University
- Brief Summary
The purpose of this study is to evaluate the effect of Low Molecular Weight Heparin (LMWH) (Fragmin, dalteparin) versus Unfractionated Heparin (UFH) on the primary outcome of proximal leg Deep Vein Thrombosis (DVT) diagnosed by compression ultrasound, and the secondary outcomes of Pulmonary Embolism (PE), bleeding, Heparin-Induced Thrombocytopenia (HIT), and objectively confirmed venous thrombosis at any site.
- Detailed Description
PROTECT: The PROphylaxis for ThromboEmbolism in Critical Care Trial.
Background: Critically ill patients have an increased risk of deep venous thrombosis (DVT) due to their acute illness, procedures such as central venous catheterization, and immobility. Among patients in the intensive care unit (ICU), DVT is an important problem, since thrombus propagation and embolization can lead to potentially fatal pulmonary embolism (PE). Only 1 randomized trial (n=119) in medical-surgical ICU patients demonstrates that unfractionated heparin (UFH) prevents DVT compared to no prophylaxis; only 1 randomized trial (n=223) in ventilated COPD patients shows that low molecular weight heparin (LMWH) prevents DVT compared to no prophylaxis. In medical-surgical ICUs, the effect of LMWH vs UFH for DVT prevention has not been tested. On one hand, LMWH is likely to be more effective at venous thromboembolism (VTE) prevention and is associated with a lower rate of heparin-induced thrombocytopenia (HIT). On the other hand, UFH is likely associated with less bleeding, and is less expensive. Current guidelines indicate that in the absence of comparative data, both LMWH and UFH are suitable for thromboprophylaxis in this population, but that a randomized trial is needed.
PROTECT Pilot: In our Pilot Study, feasibility objectives were to assess:
1) timely enrolment and complete, blinded study drug administration, 2) the bioaccumulation of LMWH in patients with acquired renal insufficiency, 3) twice weekly leg ultrasounds, and 4) recruitment rates.
1. Timely, complete administration occurred for 98% of scheduled doses; every dose was blinded.
2. No LWMH bioaccumulation was observed.
3. Scheduled ultrasounds occurred without exception.
4. Recruitment will be 4 patients/month/centre after modification of 3 exclusion criteria in the PROTECT pilot.
Objective: To evaluate the effect of LMWH (dalteparin) vs UFH on the primary outcome of proximal leg DVT diagnosed by compression ultrasound, and the secondary outcomes of PE, bleeding, HIT, and objectively confirmed venous thrombosis at any site.
Design: Prospective randomized stratified concealed blinded multicentre trial.
Population: Inclusion Criteria: Eligible patients in medical-surgical ICUs will be \>18 years old, weigh \> 45 kg, and have an expected ICU stay \> 72 hours.
Exclusion Criteria: Patients admitted to ICU post trauma, orthopedic surgery, or neurosurgery, with severe hypertension, DVT, PE or major hemorrhage within 3 months, International Normalized Ratio (INR) \> 2 ULN, Partial Thromboplastin Time (PTT) \> 2 ULN, platelets \< 75 x 109/L, or those requiring therapeutic anticoagulation will be excluded. Patients with a contraindication to heparin, blood products or pork products, with \> 3 days of LMWH or UFH in ICU, patients who are pregnant, undergoing withdrawal of life support, or are enrolled in this or a related trial will also be excluded.
Methods: Using centralized telephone randomization, we will allocate 3,650 patients in 40 centres to LMWH (dalteparin) 5,000 IU daily or UFH 5,000 IU twice daily SC for the duration of ICU stay. Patients, families, all clinicians and researcher will be blinded; only the pharmacist will be aware of allocation. Bilateral proximal leg compression ultrasounds will be performed within 48h of ICU admission, twice weekly, and on suspicion of DVT. PE will be diagnosed by a predefined diagnostic algorithm. We will record bleeding, HIT, other venous thrombosis and complications. Protocol adherence will be maximized using training, manuals, study aids, site visits, audit and feedback. Blinded Adjudication Committees will adjudicate endpoints. PROTECT will be conducted by the Canadian Critical Care Trials Group and overseen by an independent DSMB.
Relevance: The results of PROTECT will be used to develop evidence based practice guidelines regarding the safety and efficacy of LMWH (dalteparin) vs UFH for thromboprophylaxis in medical-surgical ICU patients around the world.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3659
- Patient is >/= 18 years of age
- Actual body weight is >/= 45 kg
- Admission to ICU expected to be >/= 72 hours in duration
- Neurosurgery within last 3 months
- Ischemic stroke within last 3 months
- Intracranial hemorrhage within last 3 months
- Systolic Blood Pressure >/= 180mm Hg, Diastolic Blood Pressure >/= 110mm Hg for >/= 12 hours requiring vasoactive drug infusion
- Major hemorrhage within last week unless definitively treated
- Coagulopathy as defined by INR >/= 2 times upper limit of normal [ULN], or PTT >/= 2 times ULN, at time of screening
- Thrombocytopenia defined as platelet count </= 75 x 109/L, at time of screening
- Other heparin contraindications (e.g., HIT, pregnancy, lactating)
- Contraindication to blood products (e.g., Jehovah's Witness)
- Unable to perform lower limb ultrasound (e.g., bilateral above the knee amputation, or severe distal extremity burns)
- Limitation of life support, Life expectancy </= 14 days, or palliative care
- Contamination (e.g., >/= 3 doses of LMWH during this ICU admission)
- Lack of informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LMWH (Fragmin, dalteparin) LMWH (Fragmin, dalteparin) Placebo dose (normal saline) = AM dose LMWH (Fragmin, dalteparin) 5000IU daily = PM dose 2 Unfractionated Heparin Unfractionated Heparin 5000IU BID
- Primary Outcome Measures
Name Time Method To evaluate the effect of LMWH (Fragmin, dalteparin) versus UFH on the primary outcome of proximal leg DVT diagnosed by compression ultrasound While in ICU to a maximum of 90 days
- Secondary Outcome Measures
Name Time Method To evaluate the effect of LMWH (Fragmin, dalteparin) versus UFH on the secondary outcomes of PE, bleeding, HIT, and objectively confirmed venous thrombosis at any site While in ICU to a maximum of 90 days
Trial Locations
- Locations (67)
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Sunnybrook and Women's College Health Science Centre
🇨🇦Toronto, Ontario, Canada
St Michaels Hospital
🇨🇦Toronto, Ontario, Canada
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
University Health Network - Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
Sherbrooke University (CHUS) Hospital
🇨🇦Sherbrooke, Quebec, Canada
Wollongong Hospital
🇦🇺Wollongong, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Austin Hill Hospital
🇦🇺Heidelburg, Victoria, Australia
The Geelong Hospital
🇦🇺Geelong, Victoria, Australia
Bendigo Health Care
🇦🇺Bendigo, Victoria, Australia
Hospital ProCardiaco
🇧🇷Rio de Janeiro, Brazil
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Flinders Hospital
🇦🇺Bedford Park, Victoria, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Foothills Hospital
🇨🇦Calgary, Alberta, Canada
St. John's Mercy Medical Center
🇺🇸St. Louis, Missouri, United States
Riyadh Military Hospital
🇸🇦Riyadh, Saudi Arabia
King Abdulaziz University Hospital
🇸🇦Jeddah, Saudi Arabia
MD Anderson
🇺🇸Houston, Texas, United States
Dandenong Hospital
🇦🇺Dandenong, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Nepean Hospital
🇦🇺Penrith, New South Wales, Australia
Monash Medical Center
🇦🇺Clayton, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Hospitalar Santa Casa
🇧🇷Porto Alegre, RS, Brazil
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
Royal North Shore Hospital
🇦🇺St Leonards, Australia
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Rs Cep, Brazil
Hospital Coracao
🇧🇷Sao Paulo, Brazil
Royal Alexandra Hospital
🇨🇦Edmonton, Alberta, Canada
UTI da Enfermaria de Clinical Medica do Hospital
🇧🇷Sao Paulo, Brazil
The Peter Lougheed Hospital
🇨🇦Calgary, Alberta, Canada
Surry Memorial
🇨🇦Surrey, British Columbia, Canada
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Guelph General Hospital
🇨🇦Guelph, Ontario, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
St. Boniface Hospital
🇨🇦Winnipeg, Manitoba, Canada
Queen Elizabeth II Health
🇨🇦Halifax, Nova Scotia, Canada
Hamilton Health Science Centre - Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada
St Joseph's HealthCare
🇨🇦Hamilton, Ontario, Canada
Hamilton Health Science Centre - McMaster University
🇨🇦Hamilton, Ontario, Canada
Lakeridge Health
🇨🇦Oshawa, Ontario, Canada
Hamilton Health Science Center - Henderson Hospital
🇨🇦Hamilton, Ontario, Canada
Grand River Hospital
🇨🇦Kitchener, Ontario, Canada
London Health Science Center
🇨🇦London, Ontario, Canada
Ottawa Hospital - General Hospital
🇨🇦Ottawa, Ontario, Canada
Ottawa Hospital - Civic Site
🇨🇦Ottawa, Ontario, Canada
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Hopital Maisonneuve
🇨🇦Montreal, Quebec, Canada
Montreal General Hospital, McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Royal Victoria Hospital, McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Hopital Charles LeMoyne
🇨🇦Montreal, Quebec, Canada
Hopital Sacre Couer
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Affilie-Enfant Jesus
🇨🇦Quebec City, Quebec, Canada
Hopital Laval
🇨🇦Quebec, Canada
King Faisal Specialist & Research Center
🇸🇦Jeddah, Saudi Arabia
King Abdulaziz Medical City Hospital
🇸🇦Riyadh, Riyahd, Saudi Arabia
King Fahad Medical City
🇸🇦Riyadh, Saudi Arabia
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Royal Columbian Hospital
🇨🇦Vancouver, British Columbia, Canada
Vancouver Island Health Authority
🇨🇦Victoria, British Columbia, Canada
Guys and St Thomas Hospital
🇬🇧London, England, United Kingdom
St Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States