PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00182143
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : January 10, 2011
Canadian Institutes of Health Research (CIHR)
Canadian Critical Care Trials Group
Australian and New Zealand Intensive Care Society Clinical Trials Group
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Critical Illness Deep Venous Thrombosis Drug: LMWH (Fragmin, dalteparin) Drug: Unfractionated Heparin Phase 3

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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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3659 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
Study Start Date : May 2006
Actual Primary Completion Date : June 2010
Actual Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: LMWH (Fragmin, dalteparin)
Placebo dose (normal saline) = AM dose LMWH (Fragmin, dalteparin) 5000IU daily = PM dose
Drug: LMWH (Fragmin, dalteparin)
Placebo AM dose (normal saline) and LMWH (Fragmin, dalteparin) 5000IU PM dose
Other Name: Fragmin

Active Comparator: 2
Unfractionated Heparin 5000IU BID
Drug: Unfractionated Heparin
5000 IU BID
Other Name: Heparin Sodium

Primary Outcome Measures :
  1. To evaluate the effect of LMWH (Fragmin, dalteparin) versus UFH on the primary outcome of proximal leg DVT diagnosed by compression ultrasound [ Time Frame: While in ICU to a maximum of 90 days ]

Secondary Outcome Measures :
  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 [ Time Frame: While in ICU to a maximum of 90 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 </= 75 x 109/L, at time of screening
  8. Other heparin contraindications (e.g., HIT, pregnancy, lactating)
  9. Contraindication to blood products (e.g., Jehovah's Witness)
  10. Unable to perform lower limb ultrasound (e.g., bilateral above the knee amputation, or severe distal extremity burns)
  11. Limitation of life support, Life expectancy </= 14 days, or palliative care
  12. Contamination (e.g., >/= 3 doses of LMWH during this ICU admission)
  13. Lack of informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00182143

  Hide Study Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
St. John's Mercy Medical Center
St. Louis, Missouri, United States, 63141
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
MD Anderson
Houston, Texas, United States, 77030
Australia, New South Wales
Blacktown Hospital
Blacktown, New South Wales, Australia, 2148
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Nepean Hospital
Penrith, New South Wales, Australia
Wollongong Hospital
Wollongong, New South Wales, Australia
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, Australia, 5112
Australia, Victoria
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, Australia, 3168
Frankston Hospital
Frankston, Victoria, Australia
The Geelong Hospital
Geelong, Victoria, Australia, 3220
Austin Hill Hospital
Heidelburg, Victoria, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3101
The Alfred Hospital
Melbourne, Victoria, Australia, 3181
Royal North Shore Hospital
St Leonards, Australia, NSW 2065
Hospital Moinhos de Vento
Porto Alegre, Rs Cep, Brazil, 90035-001
Hospitalar Santa Casa
Porto Alegre, RS, Brazil, 90020-200
Hospital ProCardiaco
Rio de Janeiro, Brazil
Hospital Coracao
Sao Paulo, Brazil
UTI da Enfermaria de Clinical Medica do Hospital
Sao Paulo, Brazil
Canada, Alberta
Foothills Hospital
Calgary, Alberta, Canada, T2N 2T9
The Peter Lougheed Hospital
Calgary, Alberta, Canada, TiY 6J4
Royal Alexandra Hospital
Edmonton, Alberta, Canada, T5H 3V9
University of Alberta
Edmonton, Alberta, Canada
Canada, British Columbia
Surry Memorial
Surrey, British Columbia, Canada
Royal Columbian Hospital
Vancouver, British Columbia, Canada, V3L 3W4
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
St Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Vancouver Island Health Authority
Victoria, British Columbia, Canada
Canada, Manitoba
St. Boniface Hospital
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Nova Scotia
Queen Elizabeth II Health
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Guelph General Hospital
Guelph, Ontario, Canada
Hamilton Health Science Centre - Hamilton General Hospital
Hamilton, Ontario, Canada, L8N 3Z5
Hamilton Health Science Centre - McMaster University
Hamilton, Ontario, Canada, L8N 3Z5
St Joseph's HealthCare
Hamilton, Ontario, Canada, L8N 4A6
Hamilton Health Science Center - Henderson Hospital
Hamilton, Ontario, Canada
Kingston General Hospital
Kingston, Ontario, Canada, K7L 2V7
Grand River Hospital
Kitchener, Ontario, Canada, N2G 1G3
London Health Science Center
London, Ontario, Canada
Lakeridge Health
Oshawa, Ontario, Canada
Ottawa Hospital - General Hospital
Ottawa, Ontario, Canada, K1H 8L6
Ottawa Hospital - Civic Site
Ottawa, Ontario, Canada, K1Y 4E9
Sunnybrook and Women's College Health Science Centre
Toronto, Ontario, Canada, M4N 3M5
St Michaels Hospital
Toronto, Ontario, Canada, M5B 1W8
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
University Health Network - Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
Toronto General Hospital
Toronto, Ontario, Canada
Canada, Quebec
Royal Victoria Hospital, McGill University Health Center
Montreal, Quebec, Canada, H3A 1A1
Montreal General Hospital, McGill University Health Centre
Montreal, Quebec, Canada, H3G 1A4
Hopital Sacre Couer
Montreal, Quebec, Canada, H4J 2C5
Hopital Charles LeMoyne
Montreal, Quebec, Canada, J4V 2H1
Hopital Maisonneuve
Montreal, Quebec, Canada
Centre Hospitalier Affilie-Enfant Jesus
Quebec City, Quebec, Canada, G1J 1Z4
Sherbrooke University (CHUS) Hospital
Sherbrooke, Quebec, Canada, J1H 5N4
Hopital Laval
Quebec, Canada, G1V 4G5
Saudi Arabia
King Abdulaziz Medical City Hospital
Riyadh, Riyahd, Saudi Arabia, 11426
King Abdulaziz University Hospital
Jeddah, Saudi Arabia, 21418
King Faisal Specialist & Research Center
Jeddah, Saudi Arabia
King Fahad Medical City
Riyadh, Saudi Arabia
Riyadh Military Hospital
Riyadh, Saudi Arabia
United Kingdom
Guys and St Thomas Hospital
London, England, United Kingdom
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Canadian Critical Care Trials Group
Australian and New Zealand Intensive Care Society Clinical Trials Group
Principal Investigator: Deborah J Cook, MD McMaster University

Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: McMaster University Identifier: NCT00182143     History of Changes
Other Study ID Numbers: ISRCTN54618366
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: January 10, 2011
Last Verified: October 2007

Keywords provided by McMaster University:
Critically Ill
Deep Venous ThromboEmbolism
Randomized Controlled Trial

Additional relevant MeSH terms:
Critical Illness
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Disease Attributes
Pathologic Processes
Calcium heparin
Heparin, Low-Molecular-Weight
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action