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PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)

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ClinicalTrials.gov Identifier: NCT00182143
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : January 10, 2011
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

Tracking Information
First Submitted Date  ICMJE September 10, 2005
First Posted Date  ICMJE September 16, 2005
Last Update Posted Date January 10, 2011
Study Start Date  ICMJE May 2006
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2011)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2005)
To evaluate the effect of LMWH vs UFH on the primary outcome of proximal leg DVT diagnosed by compression ultrasound.
Change History Complete list of historical versions of study NCT00182143 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2011)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2005)
To evaluate the effect of LMWH vs UFH on the secondary outcomes of PE, bleeding, HIT, and objectively confirmed venous thrombosis at any site.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
Official Title  ICMJE PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Critical Illness
  • Deep Venous Thrombosis
Intervention  ICMJE
  • Drug: LMWH (Fragmin, dalteparin)
    Placebo AM dose (normal saline) and LMWH (Fragmin, dalteparin) 5000IU PM dose
    Other Name: Fragmin
  • Drug: Unfractionated Heparin
    5000 IU BID
    Other Name: Heparin Sodium
Study Arms  ICMJE
  • Active Comparator: LMWH (Fragmin, dalteparin)
    Placebo dose (normal saline) = AM dose LMWH (Fragmin, dalteparin) 5000IU daily = PM dose
    Intervention: Drug: LMWH (Fragmin, dalteparin)
  • Active Comparator: 2
    Unfractionated Heparin 5000IU BID
    Intervention: Drug: Unfractionated Heparin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 7, 2011)
3659
Original Enrollment  ICMJE
 (submitted: September 10, 2005)
3600
Actual Study Completion Date  ICMJE June 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   Saudi Arabia,   United Kingdom,   United States
Removed Location Countries Singapore
 
Administrative Information
NCT Number  ICMJE NCT00182143
Other Study ID Numbers  ICMJE ISRCTN54618366
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party McMaster University
Study Sponsor  ICMJE McMaster University
Collaborators  ICMJE
  • Canadian Institutes of Health Research (CIHR)
  • Canadian Critical Care Trials Group
  • Australian and New Zealand Intensive Care Society Clinical Trials Group
Investigators  ICMJE
Principal Investigator: Deborah J Cook, MD McMaster University
PRS Account McMaster University
Verification Date October 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP