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Trial registered on ANZCTR


Registration number
ACTRN12606000090516
Ethics application status
Approved
Date submitted
25/02/2006
Date registered
6/03/2006
Date last updated
13/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
PROphylaxis of ThromboEmbolism in Critical Care Trial (PROTECT)
Scientific title
A randomized phase III study to compare the effects of low-molecular weight heparin and unfractionated heparin in the prevention of proximal deep vein thrombosis in a critically ill population
Secondary ID [1] 245 0
NCT00182143
Secondary ID [2] 246 0
ISRCTN94385648
Universal Trial Number (UTN)
Trial acronym
PROTECT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thromboembolism 1054 0
Condition category
Condition code
Cardiovascular 1135 1135 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will undergo concealed random allocation to LMWH (dalteparin 5,000 IU once daily, the experimental intervention) subcutaneously. The control intervention represents standard thromboprophylaxis in Canada and Australia for these ICU patients, as we have documented in surveys [Cook 2001, Cooper 2005], cross-sectional studies [Cook 2001, Lacherade] and a longitudinal study [Cook 2003]. We will prepare LMWH syringes that contain 5,000 IU of dalteparin. UFH syringes will contain 5,000 IU of UFH. Syringes of LMWH and UFH will appear identical. Patients allocated to LMWH will also receive one placebo injection daily to maintain blinding. For patients allocated to LMWH, the first dose, or the morning dose in each study kit will always be placebo and nurses will administer the numbered doses sequentially. This is to optimize the likelihood that the patients enrolled later in the day into the LMWH arm will receive active drug on study day 1. Nurses will administer study drug at approximately 1100h (+1 hour) (placebo or UFH) and 2300h (+1 hour) (dalteparin or UFH). Study drug will be administered for the duration of the ICU stay.
Bilateral proximal leg compression ultrasounds will be performed within 48hours of enrolment, twice weekly, and on suspicion of DVT.
Intervention code [1] 916 0
Prevention
Comparator / control treatment
Patients will undergo concealed random allocation to UFH (5,000 IU bid, the control intervention) subcutaneously.
Control group
Active

Outcomes
Primary outcome [1] 1520 0
Proximal DVT (symptomatic or asymptomatic DVT) diagnosed by bilateral lower extremity compression ultrasound.
Timepoint [1] 1520 0
Outcome measured: 48 hours of enrolment, twice weekly during ICU stay and upon suspicion of VTE.
Secondary outcome [1] 2749 0
1) pulmonary embolism (PE)
Timepoint [1] 2749 0
Measured during the ICU and hospital duration.
Secondary outcome [2] 2750 0
2) bleeding
Timepoint [2] 2750 0
Measured during the ICU and hospital duration.
Secondary outcome [3] 2751 0
3) Heparin Induced Thrombocytopenia (HIT)
Timepoint [3] 2751 0
Measured during the ICU and hospital duration.
Secondary outcome [4] 2752 0
4) other clinically suspected, objectively confirmed venous thrombosis.
Timepoint [4] 2752 0
Measured during the ICU and hospital duration.
Secondary outcome [5] 2753 0
As always in ICU studies, we will record ICU length of stay, ICU mortality, hospital length of stay and hospital mortality.
Timepoint [5] 2753 0
Measured during the ICU and hospital duration.

Eligibility
Key inclusion criteria
Actual body weight >45 kgAdmission to ICU expected to be >72 hours durationEligible for either UFH or LWMH thromboprophylaxis.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contraindication to prophylactic heparinNeurosurgery within last 3 monthsIschemic or hemorrhagic stroke within last 3 monthsIntracranial hemorrhage, within last 3 monthsSystolic blood pressure (SBP) > 180 mmHg, diastolic blood pressure > 110 mmHg for > 12 hours requiring vasoactive drug infusionMajor hemorrhage within the last week unless definitively treated (e.g., AAA repair)Coagulopathy (INR > 2 x ULN, or PTT > 2 x ULN)Thrombocytopenia (platelet count < 75 x 109/L)Other heparin contraindications (e.g., HIT, pregnancy)Contraindications to blood products (e.g., Jehovah’s Witness)Unable to perform lower limb ultrasound (e.g., severe distal extremity burns)Limitation of life support (life expectancy < 7 days, or palliative care Contamination (e.g., > 3 days of any UFH or LMWH prophylaxis during this ICU admission).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A centralized computerized web based or phone-in randomization system will ensure concealed randomization, through either method used, as per the preference of each center.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The McMaster Methods Center will prepare a computer generated randomization schedule.Patients will be randomized 1:1 (LMWH:UFH) using randomly variable block sizes. We will stratify patients by center and medical versus surgical admission status for 2 main reasons. First, surgical ICU patients may have a higher risk of VTE than medical patients. Second, our Canadian cross-sectional study showed differences in UFH prophylaxis prescribing between medical and surgical patients; 1-2 doses were often deferred or omitted immediately post-operatively when patients were still mechanically ventilated, and sometimes when patients had an epidural catheter [Cook 2001].
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 287 0
Canada
State/province [1] 287 0
Country [2] 288 0
Brazil
State/province [2] 288 0
Country [3] 289 0
United States of America
State/province [3] 289 0
Country [4] 290 0
Saudi Arabia
State/province [4] 290 0

Funding & Sponsors
Funding source category [1] 1236 0
Government body
Name [1] 1236 0
Canadian Institute of Health Research
Country [1] 1236 0
Canada
Primary sponsor type
University
Name
McMaster University
Address
1200 Main Stree West, Hamilton ON
Country
Canada
Secondary sponsor category [1] 1094 0
None
Name [1] 1094 0
none
Address [1] 1094 0
Country [1] 1094 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2566 0
St Joseph's Hospital
Ethics committee address [1] 2566 0
Ethics committee country [1] 2566 0
Canada
Date submitted for ethics approval [1] 2566 0
Approval date [1] 2566 0
28/12/2005
Ethics approval number [1] 2566 0
Ethics committee name [2] 2567 0
QEII Halifax
Ethics committee address [2] 2567 0
Ethics committee country [2] 2567 0
Canada
Date submitted for ethics approval [2] 2567 0
Approval date [2] 2567 0
19/12/2005
Ethics approval number [2] 2567 0
Ethics committee name [3] 2568 0
Maisonneuve Rosemont
Ethics committee address [3] 2568 0
Ethics committee country [3] 2568 0
Canada
Date submitted for ethics approval [3] 2568 0
Approval date [3] 2568 0
12/01/2006
Ethics approval number [3] 2568 0
Ethics committee name [4] 2569 0
Westminster General Hospital
Ethics committee address [4] 2569 0
Ethics committee country [4] 2569 0
Canada
Date submitted for ethics approval [4] 2569 0
Approval date [4] 2569 0
10/01/2006
Ethics approval number [4] 2569 0
Ethics committee name [5] 2570 0
The Alfred Hosptial
Ethics committee address [5] 2570 0
Ethics committee country [5] 2570 0
Australia
Date submitted for ethics approval [5] 2570 0
Approval date [5] 2570 0
09/01/2006
Ethics approval number [5] 2570 0
Ethics committee name [6] 2571 0
Surry Memorial Hospital
Ethics committee address [6] 2571 0
Ethics committee country [6] 2571 0
Canada
Date submitted for ethics approval [6] 2571 0
Approval date [6] 2571 0
10/01/2006
Ethics approval number [6] 2571 0
Ethics committee name [7] 2572 0
University of Alberta
Ethics committee address [7] 2572 0
Ethics committee country [7] 2572 0
Canada
Date submitted for ethics approval [7] 2572 0
Approval date [7] 2572 0
23/12/2006
Ethics approval number [7] 2572 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36091 0
Dr Deborah Cook
Address 36091 0
St Joseph's Healthcare Hamilton
50 Charlton Ave E, Martha Building H327
Hamilton ON, L8N 4A6

Country 36091 0
Canada
Phone 36091 0
1-905-522-1155
Fax 36091 0
Email 36091 0
Contact person for public queries
Name 10105 0
Dr Deborah Cook
Address 10105 0
St Josephs Hospital
50 Charlton Avenue E, Rm H327-1
Hamilton ON
L8N 4A6
Country 10105 0
Canada
Phone 10105 0
1-905-522-1155 ext.35325
Fax 10105 0
1-905-308-7223
Email 10105 0
Contact person for scientific queries
Name 1033 0
Dr Deborah Cook
Address 1033 0
St Josephs Hospital
50 Charlton Avenue E, Rm H327-1
Hamilton ON
L8N 4A6
Country 1033 0
Canada
Phone 1033 0
1-905-522-1155 ext 35325
Fax 1033 0
1-905-308-7223
Email 1033 0

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.