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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00182143
Other study ID # ISRCTN54618366
Secondary ID
Status Completed
Phase Phase 3
First received September 10, 2005
Last updated January 7, 2011
Start date May 2006
Est. completion date June 2010

Study information

Verified date October 2007
Source McMaster University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 3659
Est. completion date June 2010
Est. primary completion date June 2010
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
LMWH (Fragmin, dalteparin)
Placebo AM dose (normal saline) and LMWH (Fragmin, dalteparin) 5000IU PM dose
Unfractionated Heparin
5000 IU BID

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide South Australia
Australia Flinders Hospital Bedford Park Victoria
Australia Bendigo Health Care Bendigo Victoria
Australia Blacktown Hospital Blacktown New South Wales
Australia Box Hill Hospital Box Hill Victoria
Australia Royal Prince Alfred Hospital Camperdown New South Wales
Australia Monash Medical Center Clayton Victoria
Australia Dandenong Hospital Dandenong Victoria
Australia Lyell McEwin Hospital Elizabeth Vale South Australia
Australia Frankston Hospital Frankston Victoria
Australia The Geelong Hospital Geelong Victoria
Australia Austin Hill Hospital Heidelburg Victoria
Australia Royal Melbourne Hospital Melbourne Victoria
Australia The Alfred Hospital Melbourne Victoria
Australia Nepean Hospital Penrith New South Wales
Australia Royal North Shore Hospital St Leonards
Australia Wollongong Hospital Wollongong New South Wales
Brazil Hospital Moinhos de Vento Porto Alegre Rs Cep
Brazil Hospitalar Santa Casa Porto Alegre RS
Brazil Hospital ProCardiaco Rio de Janeiro
Brazil Hospital Coracao Sao Paulo
Brazil UTI da Enfermaria de Clinical Medica do Hospital Sao Paulo
Canada Foothills Hospital Calgary Alberta
Canada The Peter Lougheed Hospital Calgary Alberta
Canada Royal Alexandra Hospital Edmonton Alberta
Canada University of Alberta Edmonton Alberta
Canada Guelph General Hospital Guelph Ontario
Canada Queen Elizabeth II Health Halifax Nova Scotia
Canada Hamilton Health Science Center - Henderson Hospital Hamilton Ontario
Canada Hamilton Health Science Centre - Hamilton General Hospital Hamilton Ontario
Canada Hamilton Health Science Centre - McMaster University Hamilton Ontario
Canada St Joseph's HealthCare Hamilton Ontario
Canada Kingston General Hospital Kingston Ontario
Canada Grand River Hospital Kitchener Ontario
Canada London Health Science Center London Ontario
Canada Hopital Charles LeMoyne Montreal Quebec
Canada Hopital Maisonneuve Montreal Quebec
Canada Hopital Sacre Couer Montreal Quebec
Canada Montreal General Hospital, McGill University Health Centre Montreal Quebec
Canada Royal Victoria Hospital, McGill University Health Center Montreal Quebec
Canada Lakeridge Health Oshawa Ontario
Canada Ottawa Hospital - Civic Site Ottawa Ontario
Canada Ottawa Hospital - General Hospital Ottawa Ontario
Canada Hopital Laval Quebec
Canada Centre Hospitalier Affilie-Enfant Jesus Quebec City Quebec
Canada Sherbrooke University (CHUS) Hospital Sherbrooke Quebec
Canada Surry Memorial Surrey British Columbia
Canada Mount Sinai Hospital Toronto Ontario
Canada St Michaels Hospital Toronto Ontario
Canada Sunnybrook and Women's College Health Science Centre Toronto Ontario
Canada Toronto General Hospital Toronto Ontario
Canada University Health Network - Toronto Western Hospital Toronto Ontario
Canada Royal Columbian Hospital Vancouver British Columbia
Canada St Paul's Hospital Vancouver British Columbia
Canada Vancouver General Hospital Vancouver British Columbia
Canada Vancouver Island Health Authority Victoria British Columbia
Canada St. Boniface Hospital Winnipeg Manitoba
Saudi Arabia King Abdulaziz University Hospital Jeddah
Saudi Arabia King Faisal Specialist & Research Center Jeddah
Saudi Arabia King Abdulaziz Medical City Hospital Riyadh Riyahd
Saudi Arabia King Fahad Medical City Riyadh
Saudi Arabia Riyadh Military Hospital Riyadh
United Kingdom Guys and St Thomas Hospital London England
United States MD Anderson Houston Texas
United States Rhode Island Hospital Providence Rhode Island
United States Mayo Clinic Rochester Minnesota
United States St. John's Mercy Medical Center St. Louis Missouri

Sponsors (4)

Lead Sponsor Collaborator
McMaster University Australian and New Zealand Intensive Care Society Clinical Trials Group, Canadian Critical Care Trials Group, Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Saudi Arabia,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
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