PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00182143
First received: September 10, 2005
Last updated: January 7, 2011
Last verified: October 2007
  Purpose

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 Intervention Phase
Critical Illness
Deep Venous Thrombosis
Drug: LMWH (Fragmin, dalteparin)
Drug: Unfractionated Heparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 3659
Study Start Date: May 2006
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182143

  Show 67 Study Locations
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
Investigators
Principal Investigator: Deborah J Cook, MD McMaster University
  More Information

No publications provided by McMaster University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT00182143     History of Changes
Other Study ID Numbers: ISRCTN54618366
Study First Received: September 10, 2005
Last Updated: January 7, 2011
Health Authority: Canada: Health Canada

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

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

ClinicalTrials.gov processed this record on August 28, 2014