Prophylaxis for Thromboembolism in Critical Care Trial - PROTECT (Dalteparin vs. UFH)

Mar 22, 2011
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Australian and New Zealand College of Anesthetists Research Foundation
Date Published:
01/01/2011
Date Updated:
03/22/2011
Original Posted Date:
03/22/2011
References

Description:

The goal of the trial was to compare treatment with a low-molecular weight heparin (LMWH) compared with unfractionated heparin (UFH) in critically ill patients.

Hypothesis:

LMWH will be more effective than UFH in thromboprophylaxis prevention.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patient Populations:

  • Patients at least 18 years of age, expected to remain in an ICU for at least 3 days
  • Weight at least 45 kg

    Number of enrollees: 3,746
    Duration of follow-up: Until death or hospital discharge
    Mean patient age: 61 years
    Percentage female: 44%

Exclusions:

  • Major trauma
  • Neurosurgery or orthopedic surgery
  • Need for therapeutic anticoagulation
  • Heparin administration in the ICU for at least 3 days
  • Contraindication to heparin or blood products
  • Pregnancy
  • Life-support limitation
  • Enrollment in a related trial

Primary Endpoints:

  • Proximal leg deep-vein thrombosis
  • Ultrasound of the lower extremities was performed within 2 days of hospital admission, then twice weekly until death or hospital discharge.

Secondary Endpoints:

  • Pulmonary embolism
  • Any deep-vein thrombosis
  • Major bleeding
  • Heparin-induced thrombocytopenia
  • Death
  • Composite of venous thromboembolism or death

Drug/Procedures Used:

Patients in the intensive care unit (ICU) were randomized to LMWH (dalteparin 5000 IU subcutaneous once daily with placebo once daily, n = 1,873) versus UFH 5000 IU subcutaneous twice daily (n = 1,873). Study drug was maintained while patients were in the ICU.

Principal Findings:

Overall 3,746 patients were randomized. In the LMWH group, the mean age was 61 years, 44% were female, and body mass index was 28 kg/m2. The presenting diagnosis was a respiratory condition in 46%, a gastrointestinal condition in 14%, and a cardiovascular condition in 9%. Mechanical ventilation was used in 89%, vasopressors in 43%, and central venous catheterization in 83%.

The primary outcome, proximal leg deep-vein thrombosis, occurred in 5.1% of the LMWH group versus 5.8% of the UFH group (p = 0.57).

Secondary outcomes occurred with the following frequency: any deep-vein thrombosis 7.4% versus 8.6% (p = 0.54), pulmonary embolism 1.3% versus 2.3% (p = 0.01), any venous thromboembolism or death 28.3% versus 31.4% (p = 0.07), major bleeding 5.5% versus 5.6% (p = 0.98), heparin-induced thrombocytopenia 0.3% versus 0.6% (p = 0.16), and death 22.1% versus 24.5% (p = 0.21), respectively, for LMWH versus UFH.

Interpretation:

Among critically ill patients in the ICU, treatment with LMWH was not superior to UFH at preventing proximal leg deep-vein thrombosis.

All of the secondary outcomes were similar between the groups, except for pulmonary embolism, which occurred less frequently in the LMWH group. The reduction in pulmonary embolism should be interpreted with caution, especially since LMWH did not reduce proximal leg deep-vein thrombosis, any deep-vein thrombosis, or mortality.

References:

PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011;364:1305-1314.

Keywords: Intensive Care Units, Follow-Up Studies, Pulmonary Embolism, Heparin, Low-Molecular-Weight, Respiration, Artificial, Body Weight, Venous Thromboembolism, Dalteparin, Catheterization, Central Venous, Body Mass Index, Critical Illness, Hemorrhage, Thrombocytopenia


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