DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

Information source: McMaster University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Critical Illness; Deep Venous Thrombosis

Intervention: LMWH (Fragmin, dalteparin) (Drug); Unfractionated Heparin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: McMaster University

Official(s) and/or principal investigator(s):
Deborah J Cook, MD, Principal Investigator, Affiliation: McMaster University


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.

Clinical Details

Official title: PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: To evaluate the effect of LMWH (Fragmin, dalteparin) versus UFH on the primary outcome of proximal leg DVT diagnosed by compression ultrasound

Secondary outcome: 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

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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: 1. Patient is >/= 18 years of age 2. Actual body weight is >/= 45 kg 3. Admission to ICU expected to be >/= 72 hours in duration Exclusion Criteria: 1. Neurosurgery within last 3 months 2. Ischemic stroke within last 3 months 3. Intracranial hemorrhage within last 3 months 4. Systolic Blood Pressure >/= 180mm Hg, Diastolic Blood Pressure >/= 110mm Hg for >/= 12 hours requiring vasoactive drug infusion 5. Major hemorrhage within last week unless definitively treated 6. Coagulopathy as defined by INR >/= 2 times upper limit of normal [ULN], or PTT >/= 2 times ULN, at time of screening 7. Thrombocytopenia defined as platelet count /= 3 doses of LMWH during this ICU admission) 13. Lack of informed consent

Locations and Contacts

Royal North Shore Hospital, St Leonards NSW 2065, Australia

Hospital ProCardiaco, Rio de Janeiro, Brazil

Hospital Coracao, Sao Paulo, Brazil

UTI da Enfermaria de Clinical Medica do Hospital, Sao Paulo, Brazil

Hopital Laval, Quebec G1V 4G5, Canada

King Abdulaziz University Hospital, Jeddah 21418, Saudi Arabia

King Faisal Specialist & Research Center, Jeddah, Saudi Arabia

King Fahad Medical City, Riyadh, Saudi Arabia

Riyadh Military Hospital, Riyadh, Saudi Arabia

Foothills Hospital, Calgary, Alberta T2N 2T9, Canada

The Peter Lougheed Hospital, Calgary, Alberta TiY 6J4, Canada

Royal Alexandra Hospital, Edmonton, Alberta T5H 3V9, Canada

University of Alberta, Edmonton, Alberta, Canada

Surry Memorial, Surrey, British Columbia, Canada

Royal Columbian Hospital, Vancouver, British Columbia V3L 3W4, Canada

St Paul's Hospital, Vancouver, British Columbia V6Z 1Y6, Canada

Vancouver General Hospital, Vancouver, British Columbia V5Z 1M9, Canada

Vancouver Island Health Authority, Victoria, British Columbia, Canada

Guys and St Thomas Hospital, London, England, United Kingdom

St. Boniface Hospital, Winnipeg, Manitoba R2H 2A6, Canada

Mayo Clinic, Rochester, Minnesota 55905, United States

St. John's Mercy Medical Center, St. Louis, Missouri 63141, United States

Blacktown Hospital, Blacktown, New South Wales 2148, Australia

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

Nepean Hospital, Penrith, New South Wales, Australia

Wollongong Hospital, Wollongong, New South Wales, Australia

Queen Elizabeth II Health, Halifax, Nova Scotia B3H 3A7, Canada

Guelph General Hospital, Guelph, Ontario, Canada

Hamilton Health Science Center - Henderson Hospital, Hamilton, Ontario, Canada

Hamilton Health Science Centre - Hamilton General Hospital, Hamilton, Ontario L8N 3Z5, Canada

Hamilton Health Science Centre - McMaster University, Hamilton, Ontario L8N 3Z5, Canada

St Joseph's HealthCare, Hamilton, Ontario L8N 4A6, Canada

Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada

Grand River Hospital, Kitchener, Ontario N2G 1G3, Canada

London Health Science Center, London, Ontario, Canada

Lakeridge Health, Oshawa, Ontario, Canada

Ottawa Hospital - Civic Site, Ottawa, Ontario K1Y 4E9, Canada

Ottawa Hospital - General Hospital, Ottawa, Ontario K1H 8L6, Canada

Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada

St Michaels Hospital, Toronto, Ontario M5B 1W8, Canada

Sunnybrook and Women's College Health Science Centre, Toronto, Ontario M4N 3M5, Canada

Toronto General Hospital, Toronto, Ontario, Canada

University Health Network - Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada

Hopital Charles LeMoyne, Montreal, Quebec J4V 2H1, Canada

Hopital Maisonneuve, Montreal, Quebec, Canada

Hopital Sacre Couer, Montreal, Quebec H4J 2C5, Canada

Montreal General Hospital, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada

Royal Victoria Hospital, McGill University Health Center, Montreal, Quebec H3A 1A1, Canada

Centre Hospitalier Affilie-Enfant Jesus, Quebec City, Quebec G1J 1Z4, Canada

Sherbrooke University (CHUS) Hospital, Sherbrooke, Quebec J1H 5N4, Canada

Hospitalar Santa Casa, Porto Alegre, RS 90020-200, Brazil

Rhode Island Hospital, Providence, Rhode Island 02903, United States

King Abdulaziz Medical City Hospital, Riyadh, Riyahd 11426, Saudi Arabia

Hospital Moinhos de Vento, Porto Alegre, Rs Cep 90035-001, Brazil

Royal Adelaide Hospital, Adelaide, South Australia, Australia

Lyell McEwin Hospital, Elizabeth Vale, South Australia 5112, Australia

MD Anderson, Houston, Texas 77030, United States

Flinders Hospital, Bedford Park, Victoria, Australia

Bendigo Health Care, Bendigo, Victoria, Australia

Box Hill Hospital, Box Hill, Victoria, Australia

Monash Medical Center, Clayton, Victoria, Australia

Dandenong Hospital, Dandenong, Victoria 3168, Australia

Frankston Hospital, Frankston, Victoria, Australia

The Geelong Hospital, Geelong, Victoria 3220, Australia

Austin Hill Hospital, Heidelburg, Victoria, Australia

Royal Melbourne Hospital, Melbourne, Victoria 3101, Australia

The Alfred Hospital, Melbourne, Victoria 3181, Australia

Additional Information

Starting date: May 2006
Last updated: January 7, 2011

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017