PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

NCT00182143 | Completed Phase 3 DMC

• 1 other identifier: ISRCTN54618366
• Study Type: interventional
• Target: 3,659
• Locations: 6 countries
• Sites: 67

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.

Conditions

Critical Illness; Deep Venous Thrombosis

Keywords

Critically Ill; Deep Venous ThromboEmbolism; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

LMWH (Fragmin, dalteparin)

ACTIVE COMPARATOR

Placebo dose (normal saline) = AM dose LMWH (Fragmin, dalteparin) 5000IU daily = PM dose

Drug: LMWH (Fragmin, dalteparin)

2

ACTIVE COMPARATOR

Unfractionated Heparin 5000IU BID

Drug: Unfractionated Heparin

Interventions

LMWH (Fragmin, dalteparin) DRUG

Placebo AM dose (normal saline) and LMWH (Fragmin, dalteparin) 5000IU PM dose

Also known as: Fragmin

LMWH (Fragmin, dalteparin)

Unfractionated Heparin DRUG

5000 IU BID

Also known as: Heparin Sodium

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is \>/= 18 years of age
• Actual body weight is \>/= 45 kg
• Admission to ICU expected to be \>/= 72 hours in duration

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Canadian Critical Care Trials Group: collaborator
• Australian and New Zealand Intensive Care Society Clinical Trials Group: collaborator

Study Sites (67)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. John's Mercy Medical Center

St Louis, Missouri, 63141, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Location

Nepean Hospital

Penrith, New South Wales, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Flinders Hospital

Bedford Park, Victoria, Australia

Location

Bendigo Health Care

Bendigo, Victoria, Australia

Location

Box Hill Hospital

Box Hill, Victoria, Australia

Location

Monash Medical Center

Clayton, Victoria, Australia

Location

Dandenong Hospital

Dandenong, Victoria, 3168, Australia

Location

Frankston Hospital

Frankston, Victoria, Australia

Location

The Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

Austin Hill Hospital

Heidelburg, Victoria, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3101, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Royal North Shore Hospital

St Leonards, NSW 2065, Australia

Location

UTI da Enfermaria de Clinical Medica do Hospital

São Paulo, Brazil, Brazil

Location

Hospitalar Santa Casa

Porto Alegre, Rio Grande do Sul, 90020-200, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Rs Cep, 90035-001, Brazil

Location

Hospital ProCardiaco

Rio de Janeiro, Brazil

Location

Hospital Coracao

São Paulo, Brazil

Location

Foothills Hospital

Calgary, Alberta, T2N 2T9, Canada

Location

The Peter Lougheed Hospital

Calgary, Alberta, TiY 6J4, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Surry Memorial

Surrey, British Columbia, Canada

Location

Royal Columbian Hospital

Vancouver, British Columbia, V3L 3W4, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

St Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Vancouver Island Health Authority

Victoria, British Columbia, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Queen Elizabeth II Health

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Guelph General Hospital

Guelph, Ontario, Canada

Location

Hamilton Health Science Centre - Hamilton General Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Hamilton Health Science Centre - McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

Location

St Joseph's HealthCare

Hamilton, Ontario, L8N 4A6, Canada

Location

Hamilton Health Science Center - Henderson Hospital

Hamilton, Ontario, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Grand River Hospital

Kitchener, Ontario, N2G 1G3, Canada

Location

London Health Science Center

London, Ontario, Canada

Location

Lakeridge Health

Oshawa, Ontario, Canada

Location

Ottawa Hospital - General Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Ottawa Hospital - Civic Site

Ottawa, Ontario, K1Y 4E9, Canada

Location

Sunnybrook and Women's College Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St Michaels Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Toronto General Hospital

Toronto, Ontario, Canada

Location

Royal Victoria Hospital, McGill University Health Center

Montreal, Quebec, H3A 1A1, Canada

Location

Montreal General Hospital, McGill University Health Centre

Montreal, Quebec, H3G 1A4, Canada

Location

Hopital Sacre Couer

Montreal, Quebec, H4J 2C5, Canada

Location

Hopital Charles LeMoyne

Montreal, Quebec, J4V 2H1, Canada

Location

Hopital Maisonneuve

Montreal, Quebec, Canada

Location

Centre Hospitalier Affilie-Enfant Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Hopital Laval

Québec, Quebec, G1V 4G5, Canada

Location

Sherbrooke University (CHUS) Hospital

Sherbrooke, Quebec, J1H 5N4, Canada

Location

King Abdulaziz Medical City Hospital

Riyadh, Riyahd, 11426, Saudi Arabia

Location

King Abdulaziz University Hospital

Jeddah, 21418, Saudi Arabia

Location

King Faisal Specialist & Research Center

Jeddah, Saudi Arabia

Location

King Fahad Medical City

Riyadh, Saudi Arabia

Location

Riyadh Military Hospital

Riyadh, Saudi Arabia

Location

Guys and St Thomas Hospital

London, England, United Kingdom

Location

Related Publications (12)

• Li G, Cook DJ, Thabane L, Friedrich JO, Crozier TM, Muscedere J, Granton J, Mehta S, Reynolds SC, Lopes RD, Lauzier F, Freitag AP, Levine MA; PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Risk factors for mortality in patients admitted to intensive care units with pneumonia. Respir Res. 2016 Jul 11;17(1):80. doi: 10.1186/s12931-016-0397-5.

  PMID: 27401184 DERIVED

• Li G, Thabane L, Cook DJ, Lopes RD, Marshall JC, Guyatt G, Holbrook A, Akhtar-Danesh N, Fowler RA, Adhikari NKJ, Taylor R, Arabi YM, Chittock D, Dodek P, Freitag AP, Walter SD, Heels-Ansdell D, Levine MAH. Risk factors for and prediction of mortality in critically ill medical-surgical patients receiving heparin thromboprophylaxis. Ann Intensive Care. 2016 Dec;6(1):18. doi: 10.1186/s13613-016-0116-x. Epub 2016 Feb 27.

  PMID: 26921148 DERIVED

• Li G, Cook DJ, Levine MAH, Guyatt G, Crowther M, Heels-Ansdell D, Holbrook A, Lamontagne F, Walter SD, Ferguson ND, Finfer S, Arabi YM, Bellomo R, Cooper DJ, Thabane L; PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients. Medicine (Baltimore). 2015 Sep;94(36):e1479. doi: 10.1097/MD.0000000000001479.

  PMID: 26356708 DERIVED

• Fowler RA, Mittmann N, Geerts WH, Heels-Ansdell D, Gould MK, Guyatt G, Krahn M, Finfer S, Pinto R, Chan B, Ormanidhi O, Arabi Y, Qushmaq I, Rocha MG, Dodek P, McIntyre L, Hall R, Ferguson ND, Mehta S, Marshall JC, Doig CJ, Muscedere J, Jacka MJ, Klinger JR, Vlahakis N, Orford N, Seppelt I, Skrobik YK, Sud S, Cade JF, Cooper J, Cook D; Canadian Critical Care Trials Group; Australia and New Zealand Intensive Care Society Clinical Trials Group. Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial. Trials. 2014 Dec 20;15:502. doi: 10.1186/1745-6215-15-502.

  PMID: 25528663 DERIVED

• Crowther M, Cook D, Guyatt G, Zytaruk N, McDonald E, Williamson D, Albert M, Dodek P, Finfer S, Vallance S, Heels-Ansdell D, McIntyre L, Mehta S, Lamontagne F, Muscedere J, Jacka M, Lesur O, Kutsiogiannis J, Friedrich J, Klinger JR, Qushmaq I, Burry L, Khwaja K, Sheppard JA, Warkentin TE; PROTECT collaborators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial. J Crit Care. 2014 Jun;29(3):470.e7-15. doi: 10.1016/j.jcrc.2014.02.004. Epub 2014 Feb 14.

  PMID: 24726205 DERIVED

• Lamontagne F, McIntyre L, Dodek P, Heels-Ansdell D, Meade M, Pemberton J, Skrobik Y, Seppelt I, Vlahakis NE, Muscedere J, Reece G, Ostermann M, Padayachee S, Alhashemi J, Walsh M, Lewis B, Schiff D, Moody A, Zytaruk N, Leblanc M, Cook DJ; Prophylaxis for Thromboembolism in Critical Care Trial Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Nonleg venous thrombosis in critically ill adults: a nested prospective cohort study. JAMA Intern Med. 2014 May;174(5):689-96. doi: 10.1001/jamainternmed.2014.169.

  PMID: 24638843 DERIVED

• Lauzier F, Arnold DM, Rabbat C, Heels-Ansdell D, Zarychanski R, Dodek P, Ashley BJ, Albert M, Khwaja K, Ostermann M, Skrobik Y, Fowler R, McIntyre L, Nates JL, Karachi T, Lopes RD, Zytaruk N, Finfer S, Crowther M, Cook D. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med. 2013 Dec;39(12):2135-43. doi: 10.1007/s00134-013-3044-3. Epub 2013 Aug 14.

  PMID: 23942857 DERIVED

• Smith OM, McDonald E, Zytaruk N, Foster D, Matte A, Clarke F, Fleury S, Krause K, McArdle T, Skrobik Y, Cook DJ. Enhancing the informed consent process for critical care research: strategies from a thromboprophylaxis trial. Intensive Crit Care Nurs. 2013 Dec;29(6):300-9. doi: 10.1016/j.iccn.2013.04.006. Epub 2013 Jul 18.

  PMID: 23871290 DERIVED

• Williamson DR, Albert M, Heels-Ansdell D, Arnold DM, Lauzier F, Zarychanski R, Crowther M, Warkentin TE, Dodek P, Cade J, Lesur O, Lim W, Fowler R, Lamontagne F, Langevin S, Freitag A, Muscedere J, Friedrich JO, Geerts W, Burry L, Alhashemi J, Cook D; PROTECT collaborators, the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013 Oct;144(4):1207-1215. doi: 10.1378/chest.13-0121.

  PMID: 23788287 DERIVED

• Smith OM, McDonald E, Zytaruk N, Foster D, Matte A, Clarke F, Meade L, O'Callaghan N, Vallance S, Galt P, Rajbhandari D, Rocha M, Mehta S, Ferguson ND, Hall R, Fowler R, Burns K, Qushmaq I, Ostermann M, Heels-Ansdell D, Cook D; PROTECT Research Coordinators; PROTECT Investigators; Canadian Critical Care Trials Group; Australian, New Zealand Intensive Care Society Clinical Trials Group. Rates and determinants of informed consent: a case study of an international thromboprophylaxis trial. J Crit Care. 2013 Feb;28(1):28-39. doi: 10.1016/j.jcrc.2012.08.005. Epub 2012 Oct 22.

  PMID: 23089679 DERIVED

• Cook D, Meade M, Guyatt G, Walter SD, Heels-Ansdell D, Geerts W, Warkentin TE, Cooper DJ, Zytaruk N, Vallance S, Berwanger O, Rocha M, Qushmaq I, Crowther M. PROphylaxis for ThromboEmbolism in Critical Care Trial protocol and analysis plan. J Crit Care. 2011 Apr;26(2):223.e1-9. doi: 10.1016/j.jcrc.2011.02.010.

  PMID: 21482348 DERIVED

• PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, Zytaruk N, Crowther M, Geerts W, Cooper DJ, Vallance S, Qushmaq I, Rocha M, Berwanger O, Vlahakis NE. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011 Apr 7;364(14):1305-14. doi: 10.1056/NEJMoa1014475. Epub 2011 Mar 22.

  PMID: 21417952 DERIVED

Related Links

• PROTECT Collaborator Web Page

MeSH Terms

Conditions

Critical Illness; Venous Thrombosis

Interventions

Heparin, Low-Molecular-Weight; Dalteparin; Heparin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Deborah J Cook, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 10, 2005
• First Posted: September 16, 2005
• Study Start: May 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: January 10, 2011

Record last verified: 2007-10

Locations

CA (35); BR (5); SA (5); GB (1); US (4); AU (17)