Critical IllnessPhase 3NCT00182143
PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
A Phase 3 study testing LMWH (Fragmin, dalteparin) and Unfractionated Heparin in people with Critical Illness and Deep Venous Thrombosis, run by McMaster University at 67 sites in 6 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Deep Venous Thrombosis
- What is being tested?
- LMWH (Fragmin, dalteparin) and Unfractionated Heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,659 participants
- Where
- 67 sitesin 6 countries
- Study dates
- May 2006to Jun 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is >/= 18 years of age
- Actual body weight is >/= 45 kg
- Admission to ICU expected to be >/= 72 hours in duration
Who cannot join
- Neurosurgery within last 3 months
- Ischemic stroke within last 3 months
- Intracranial hemorrhage within last 3 months
- Systolic Blood Pressure >/= 180mm Hg, Diastolic Blood Pressure >/= 110mm Hg for >/= 12 hours requiring vasoactive drug infusion
- Major hemorrhage within last week unless definitively treated
- Coagulopathy as defined by INR >/= 2 times upper limit of normal [ULN], or PTT >/= 2 times ULN, at time of screening
Show all 13Show fewer
- Thrombocytopenia defined as platelet count </= 75 x 109/L, at time of screening
- Other heparin contraindications (e.g., HIT, pregnancy, lactating)
- Contraindication to blood products (e.g., Jehovah's Witness)
- Unable to perform lower limb ultrasound (e.g., bilateral above the knee amputation, or severe distal extremity burns)
- Limitation of life support, Life expectancy </= 14 days, or palliative care
- Contamination (e.g., >/= 3 doses of LMWH during this ICU admission)
- Lack of informed consent
Trial locations and contacts
67 sites in 6 countries.
67 sites in 6 countries
Canada35 sites
Foothills Hospital
Calgary, Alberta, T2N 2T9
The Peter Lougheed Hospital
Calgary, Alberta, TiY 6J4
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
University of Alberta
Edmonton, Alberta
Guelph General Hospital
Guelph, Ontario
Queen Elizabeth II Health
Halifax, Nova Scotia, B3H 3A7
Hamilton Health Science Centre - Hamilton General Hospital
Hamilton, Ontario, L8N 3Z5
Hamilton Health Science Centre - McMaster University
Hamilton, Ontario, L8N 3Z5
St Joseph's HealthCare
Hamilton, Ontario, L8N 4A6
Hamilton Health Science Center - Henderson Hospital
Hamilton, Ontario
Kingston General Hospital
Kingston, Ontario, K7L 2V7
Grand River Hospital
Kitchener, Ontario, N2G 1G3
London Health Science Center
London, Ontario
Royal Victoria Hospital, McGill University Health Center
Montreal, Quebec, H3A 1A1
Montreal General Hospital, McGill University Health Centre
Montreal, Quebec, H3G 1A4
Hopital Sacre Couer
Montreal, Quebec, H4J 2C5
Hopital Charles LeMoyne
Montreal, Quebec, J4V 2H1
Hopital Maisonneuve
Montreal, Quebec
Lakeridge Health
Oshawa, Ontario
Ottawa Hospital - General Hospital
Ottawa, Ontario, K1H 8L6
Ottawa Hospital - Civic Site
Ottawa, Ontario, K1Y 4E9
Centre Hospitalier Affilie-Enfant Jesus
Québec, Quebec, G1J 1Z4
Hopital Laval
Québec, Quebec, G1V 4G5
Sherbrooke University (CHUS) Hospital
Sherbrooke, Quebec, J1H 5N4
Surry Memorial
Surrey, British Columbia
Sunnybrook and Women's College Health Science Centre
Toronto, Ontario, M4N 3M5
St Michaels Hospital
Toronto, Ontario, M5B 1W8
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
University Health Network - Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Toronto General Hospital
Toronto, Ontario
Royal Columbian Hospital
Vancouver, British Columbia, V3L 3W4
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
St Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Vancouver Island Health Authority
Victoria, British Columbia
St. Boniface Hospital
Winnipeg, Manitoba, R2H 2A6
Australia17 sites
Royal Adelaide Hospital
Adelaide, South Australia
Flinders Hospital
Bedford Park, Victoria
Bendigo Health Care
Bendigo, Victoria
Blacktown Hospital
Blacktown, New South Wales, 2148
Box Hill Hospital
Box Hill, Victoria
Royal Prince Alfred Hospital
Camperdown, New South Wales
Monash Medical Center
Clayton, Victoria
Dandenong Hospital
Dandenong, Victoria, 3168
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112
Frankston Hospital
Frankston, Victoria
The Geelong Hospital
Geelong, Victoria, 3220
Austin Hill Hospital
Heidelburg, Victoria
Royal Melbourne Hospital
Melbourne, Victoria, 3101
The Alfred Hospital
Melbourne, Victoria, 3181
Nepean Hospital
Penrith, New South Wales
Royal North Shore Hospital
St Leonards, NSW 2065
Wollongong Hospital
Wollongong, New South Wales
Brazil5 sites
Hospitalar Santa Casa
Porto Alegre, Rio Grande do Sul, 90020-200
Hospital Moinhos de Vento
Porto Alegre, Rs Cep, 90035-001
Hospital ProCardiaco
Rio de Janeiro
UTI da Enfermaria de Clinical Medica do Hospital
São Paulo, Brazil
Hospital Coracao
São Paulo
Saudi Arabia5 sites
King Abdulaziz University Hospital
Jeddah, 21418
King Faisal Specialist & Research Center
Jeddah
King Abdulaziz Medical City Hospital
Riyadh, Riyahd, 11426
King Fahad Medical City
Riyadh
Riyadh Military Hospital
Riyadh
United States4 sites
MD Anderson
Houston, Texas, 77030
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic
Rochester, Minnesota, 55905
St. John's Mercy Medical Center
St Louis, Missouri, 63141
About this study
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.
Read the 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:
- 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.
- Timely, complete administration occurred for 98% of scheduled doses; every dose was blinded.
- No LWMH bioaccumulation was observed.
- Scheduled ultrasounds occurred without exception.
- 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.
- Conditions
- Critical Illness, Deep Venous Thrombosis
- Being tested
- LMWH (Fragmin, dalteparin), Unfractionated Heparin
- Keywords
- Critically Ill, Deep Venous ThromboEmbolism, Randomized Controlled Trial
- Medical subject headings
- Critical Illness, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LMWH (Fragmin, dalteparin)Drug
Also called Fragmin
Placebo AM dose (normal saline) and LMWH (Fragmin, dalteparin) 5000IU PM dose
Unfractionated HeparinDrug
Also called Heparin Sodium
5000 IU BID
| Study group | Role | What they receive |
|---|---|---|
| LMWH (Fragmin, dalteparin) | Active comparator | Placebo dose (normal saline) = AM dose LMWH (Fragmin, dalteparin) 5000IU daily = PM dose Receives: Drug: LMWH (Fragmin, dalteparin) |
| 2 | Active comparator | Unfractionated Heparin 5000IU BID Receives: Drug: Unfractionated Heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of LMWH (Fragmin, dalteparin) versus UFH on the primary outcome of proximal leg DVT diagnosed by compression ultrasound
Measured: While in ICU to a maximum of 90 days
Secondary outcomes (1)
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
Measured: While in ICU to a maximum of 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startMay 2006
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,659 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group
- Investigators
- Deborah J Cook, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00182143
- Sponsor's protocol ID
- ISRCTN54618366
- Status last verified
- Oct 2007
- First submitted
- 10 Sep 2005
- Last updated
- 10 Jan 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li G, Cook DJ, Thabane L, Friedrich JO, Crozier TM, Muscedere J, Granton J, Mehta S, Reynolds SC, Lopes RD, Lauzier F, Freitag AP, Levine MA; PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Risk factors for mortality in patients admitted to intensive care units with pneumonia. Respir Res. 2016 Jul 11;17(1):80. doi: 10.1186/s12931-016-0397-5.
PubMed 27401184Li G, Thabane L, Cook DJ, Lopes RD, Marshall JC, Guyatt G, Holbrook A, Akhtar-Danesh N, Fowler RA, Adhikari NKJ, Taylor R, Arabi YM, Chittock D, Dodek P, Freitag AP, Walter SD, Heels-Ansdell D, Levine MAH. Risk factors for and prediction of mortality in critically ill medical-surgical patients receiving heparin thromboprophylaxis. Ann Intensive Care. 2016 Dec;6(1):18. doi: 10.1186/s13613-016-0116-x. Epub 2016 Feb 27.
PubMed 26921148Li G, Cook DJ, Levine MAH, Guyatt G, Crowther M, Heels-Ansdell D, Holbrook A, Lamontagne F, Walter SD, Ferguson ND, Finfer S, Arabi YM, Bellomo R, Cooper DJ, Thabane L; PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients. Medicine (Baltimore). 2015 Sep;94(36):e1479. doi: 10.1097/MD.0000000000001479.
PubMed 26356708Fowler RA, Mittmann N, Geerts WH, Heels-Ansdell D, Gould MK, Guyatt G, Krahn M, Finfer S, Pinto R, Chan B, Ormanidhi O, Arabi Y, Qushmaq I, Rocha MG, Dodek P, McIntyre L, Hall R, Ferguson ND, Mehta S, Marshall JC, Doig CJ, Muscedere J, Jacka MJ, Klinger JR, Vlahakis N, Orford N, Seppelt I, Skrobik YK, Sud S, Cade JF, Cooper J, Cook D; Canadian Critical Care Trials Group; Australia and New Zealand Intensive Care Society Clinical Trials Group. Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial. Trials. 2014 Dec 20;15:502. doi: 10.1186/1745-6215-15-502.
PubMed 25528663Crowther M, Cook D, Guyatt G, Zytaruk N, McDonald E, Williamson D, Albert M, Dodek P, Finfer S, Vallance S, Heels-Ansdell D, McIntyre L, Mehta S, Lamontagne F, Muscedere J, Jacka M, Lesur O, Kutsiogiannis J, Friedrich J, Klinger JR, Qushmaq I, Burry L, Khwaja K, Sheppard JA, Warkentin TE; PROTECT collaborators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial. J Crit Care. 2014 Jun;29(3):470.e7-15. doi: 10.1016/j.jcrc.2014.02.004. Epub 2014 Feb 14.
PubMed 24726205Lamontagne F, McIntyre L, Dodek P, Heels-Ansdell D, Meade M, Pemberton J, Skrobik Y, Seppelt I, Vlahakis NE, Muscedere J, Reece G, Ostermann M, Padayachee S, Alhashemi J, Walsh M, Lewis B, Schiff D, Moody A, Zytaruk N, Leblanc M, Cook DJ; Prophylaxis for Thromboembolism in Critical Care Trial Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Nonleg venous thrombosis in critically ill adults: a nested prospective cohort study. JAMA Intern Med. 2014 May;174(5):689-96. doi: 10.1001/jamainternmed.2014.169.
PubMed 24638843Lauzier F, Arnold DM, Rabbat C, Heels-Ansdell D, Zarychanski R, Dodek P, Ashley BJ, Albert M, Khwaja K, Ostermann M, Skrobik Y, Fowler R, McIntyre L, Nates JL, Karachi T, Lopes RD, Zytaruk N, Finfer S, Crowther M, Cook D. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med. 2013 Dec;39(12):2135-43. doi: 10.1007/s00134-013-3044-3. Epub 2013 Aug 14.
PubMed 23942857Smith OM, McDonald E, Zytaruk N, Foster D, Matte A, Clarke F, Fleury S, Krause K, McArdle T, Skrobik Y, Cook DJ. Enhancing the informed consent process for critical care research: strategies from a thromboprophylaxis trial. Intensive Crit Care Nurs. 2013 Dec;29(6):300-9. doi: 10.1016/j.iccn.2013.04.006. Epub 2013 Jul 18.
PubMed 23871290Williamson DR, Albert M, Heels-Ansdell D, Arnold DM, Lauzier F, Zarychanski R, Crowther M, Warkentin TE, Dodek P, Cade J, Lesur O, Lim W, Fowler R, Lamontagne F, Langevin S, Freitag A, Muscedere J, Friedrich JO, Geerts W, Burry L, Alhashemi J, Cook D; PROTECT collaborators, the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013 Oct;144(4):1207-1215. doi: 10.1378/chest.13-0121.
PubMed 23788287Smith OM, McDonald E, Zytaruk N, Foster D, Matte A, Clarke F, Meade L, O'Callaghan N, Vallance S, Galt P, Rajbhandari D, Rocha M, Mehta S, Ferguson ND, Hall R, Fowler R, Burns K, Qushmaq I, Ostermann M, Heels-Ansdell D, Cook D; PROTECT Research Coordinators; PROTECT Investigators; Canadian Critical Care Trials Group; Australian, New Zealand Intensive Care Society Clinical Trials Group. Rates and determinants of informed consent: a case study of an international thromboprophylaxis trial. J Crit Care. 2013 Feb;28(1):28-39. doi: 10.1016/j.jcrc.2012.08.005. Epub 2012 Oct 22.
PubMed 23089679Cook D, Meade M, Guyatt G, Walter SD, Heels-Ansdell D, Geerts W, Warkentin TE, Cooper DJ, Zytaruk N, Vallance S, Berwanger O, Rocha M, Qushmaq I, Crowther M. PROphylaxis for ThromboEmbolism in Critical Care Trial protocol and analysis plan. J Crit Care. 2011 Apr;26(2):223.e1-9. doi: 10.1016/j.jcrc.2011.02.010.
PubMed 21482348PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, Zytaruk N, Crowther M, Geerts W, Cooper DJ, Vallance S, Qushmaq I, Rocha M, Berwanger O, Vlahakis NE. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011 Apr 7;364(14):1305-14. doi: 10.1056/NEJMoa1014475. Epub 2011 Mar 22.
PubMed 21417952
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
- ClinicalTrials.gov ID
- NCT00182143
- Acronym / sponsor ID
- ISRCTN54618366
- Conditions
- Critical Illness, Deep Venous Thrombosis
- Keywords
- Critically Ill, Deep Venous ThromboEmbolism, Randomized Controlled Trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,659 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group
- Study start
- May 2006
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Timely, complete administration occurred for 98% of scheduled doses; every dose was blinded.
- No LWMH bioaccumulation was observed.
- Scheduled ultrasounds occurred without exception.
- 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMWH (Fragmin, dalteparin) | Active comparator | Drug: LMWH (Fragmin, dalteparin)Placebo dose (normal saline) = AM dose LMWH (Fragmin, dalteparin) 5000IU daily = PM dose |
| 2 | Active comparator | Drug: Unfractionated HeparinUnfractionated Heparin 5000IU BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patient is >/= 18 years of age
- Actual body weight is >/= 45 kg
- Admission to ICU expected to be >/= 72 hours in duration
Key exclusion criteria (13 listed)
- Neurosurgery within last 3 months
- Ischemic stroke within last 3 months
- Intracranial hemorrhage within last 3 months
- Systolic Blood Pressure >/= 180mm Hg, Diastolic Blood Pressure >/= 110mm Hg for >/= 12 hours requiring vasoactive drug infusion
- Major hemorrhage within last week unless definitively treated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LMWH (Fragmin, dalteparin)Also: FragminPlacebo AM dose (normal saline) and LMWH (Fragmin, dalteparin) 5000IU PM dose | Drug | LMWH (Fragmin, dalteparin) |
| Unfractionated HeparinAlso: Heparin Sodium5000 IU BID | Drug | 2 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2011.
- Derived from this study: PubMed 27401184Li G, Cook DJ, Thabane L, Friedrich JO, Crozier TM, Muscedere J, Granton J, Mehta S, Reynolds SC, Lopes RD, Lauzier F, Freitag AP, Levine MA; PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Risk factors for mortality in patients admitted to intensive care units with pneumonia. Respir Res. 2016 Jul 11;17(1):80. doi: 10.1186/s12931-016-0397-5.
- Derived from this study: PubMed 26921148Li G, Thabane L, Cook DJ, Lopes RD, Marshall JC, Guyatt G, Holbrook A, Akhtar-Danesh N, Fowler RA, Adhikari NKJ, Taylor R, Arabi YM, Chittock D, Dodek P, Freitag AP, Walter SD, Heels-Ansdell D, Levine MAH. Risk factors for and prediction of mortality in critically ill medical-surgical patients receiving heparin thromboprophylaxis. Ann Intensive Care. 2016 Dec;6(1):18. doi: 10.1186/s13613-016-0116-x. Epub 2016 Feb 27.
- Derived from this study: PubMed 26356708Li G, Cook DJ, Levine MAH, Guyatt G, Crowther M, Heels-Ansdell D, Holbrook A, Lamontagne F, Walter SD, Ferguson ND, Finfer S, Arabi YM, Bellomo R, Cooper DJ, Thabane L; PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients. Medicine (Baltimore). 2015 Sep;94(36):e1479. doi: 10.1097/MD.0000000000001479.
- Derived from this study: PubMed 25528663Fowler RA, Mittmann N, Geerts WH, Heels-Ansdell D, Gould MK, Guyatt G, Krahn M, Finfer S, Pinto R, Chan B, Ormanidhi O, Arabi Y, Qushmaq I, Rocha MG, Dodek P, McIntyre L, Hall R, Ferguson ND, Mehta S, Marshall JC, Doig CJ, Muscedere J, Jacka MJ, Klinger JR, Vlahakis N, Orford N, Seppelt I, Skrobik YK, Sud S, Cade JF, Cooper J, Cook D; Canadian Critical Care Trials Group; Australia and New Zealand Intensive Care Society Clinical Trials Group. Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial. Trials. 2014 Dec 20;15:502. doi: 10.1186/1745-6215-15-502.
- Derived from this study: PubMed 24726205Crowther M, Cook D, Guyatt G, Zytaruk N, McDonald E, Williamson D, Albert M, Dodek P, Finfer S, Vallance S, Heels-Ansdell D, McIntyre L, Mehta S, Lamontagne F, Muscedere J, Jacka M, Lesur O, Kutsiogiannis J, Friedrich J, Klinger JR, Qushmaq I, Burry L, Khwaja K, Sheppard JA, Warkentin TE; PROTECT collaborators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial. J Crit Care. 2014 Jun;29(3):470.e7-15. doi: 10.1016/j.jcrc.2014.02.004. Epub 2014 Feb 14.
- Derived from this study: PubMed 24638843Lamontagne F, McIntyre L, Dodek P, Heels-Ansdell D, Meade M, Pemberton J, Skrobik Y, Seppelt I, Vlahakis NE, Muscedere J, Reece G, Ostermann M, Padayachee S, Alhashemi J, Walsh M, Lewis B, Schiff D, Moody A, Zytaruk N, Leblanc M, Cook DJ; Prophylaxis for Thromboembolism in Critical Care Trial Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Nonleg venous thrombosis in critically ill adults: a nested prospective cohort study. JAMA Intern Med. 2014 May;174(5):689-96. doi: 10.1001/jamainternmed.2014.169.
- Derived from this study: PubMed 23942857Lauzier F, Arnold DM, Rabbat C, Heels-Ansdell D, Zarychanski R, Dodek P, Ashley BJ, Albert M, Khwaja K, Ostermann M, Skrobik Y, Fowler R, McIntyre L, Nates JL, Karachi T, Lopes RD, Zytaruk N, Finfer S, Crowther M, Cook D. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med. 2013 Dec;39(12):2135-43. doi: 10.1007/s00134-013-3044-3. Epub 2013 Aug 14.
- Derived from this study: PubMed 23871290Smith OM, McDonald E, Zytaruk N, Foster D, Matte A, Clarke F, Fleury S, Krause K, McArdle T, Skrobik Y, Cook DJ. Enhancing the informed consent process for critical care research: strategies from a thromboprophylaxis trial. Intensive Crit Care Nurs. 2013 Dec;29(6):300-9. doi: 10.1016/j.iccn.2013.04.006. Epub 2013 Jul 18.
- Derived from this study: PubMed 23788287Williamson DR, Albert M, Heels-Ansdell D, Arnold DM, Lauzier F, Zarychanski R, Crowther M, Warkentin TE, Dodek P, Cade J, Lesur O, Lim W, Fowler R, Lamontagne F, Langevin S, Freitag A, Muscedere J, Friedrich JO, Geerts W, Burry L, Alhashemi J, Cook D; PROTECT collaborators, the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013 Oct;144(4):1207-1215. doi: 10.1378/chest.13-0121.
- Derived from this study: PubMed 23089679Smith OM, McDonald E, Zytaruk N, Foster D, Matte A, Clarke F, Meade L, O'Callaghan N, Vallance S, Galt P, Rajbhandari D, Rocha M, Mehta S, Ferguson ND, Hall R, Fowler R, Burns K, Qushmaq I, Ostermann M, Heels-Ansdell D, Cook D; PROTECT Research Coordinators; PROTECT Investigators; Canadian Critical Care Trials Group; Australian, New Zealand Intensive Care Society Clinical Trials Group. Rates and determinants of informed consent: a case study of an international thromboprophylaxis trial. J Crit Care. 2013 Feb;28(1):28-39. doi: 10.1016/j.jcrc.2012.08.005. Epub 2012 Oct 22.
- Derived from this study: PubMed 21482348Cook D, Meade M, Guyatt G, Walter SD, Heels-Ansdell D, Geerts W, Warkentin TE, Cooper DJ, Zytaruk N, Vallance S, Berwanger O, Rocha M, Qushmaq I, Crowther M. PROphylaxis for ThromboEmbolism in Critical Care Trial protocol and analysis plan. J Crit Care. 2011 Apr;26(2):223.e1-9. doi: 10.1016/j.jcrc.2011.02.010.
- Derived from this study: PubMed 21417952PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, Zytaruk N, Crowther M, Geerts W, Cooper DJ, Vallance S, Qushmaq I, Rocha M, Berwanger O, Vlahakis NE. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011 Apr 7;364(14):1305-14. doi: 10.1056/NEJMoa1014475. Epub 2011 Mar 22.
- PROTECT Collaborator Web PageLink provided by the sponsor.
Related trials for Critical Illness
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Recruiting
Development and Preliminary Validation of Intelligent Video Laryngoscope for Emergency Use
Critically Ill Patients Requiring Mechanical Ventilation
Active, not recruiting
Weighted Blankets for Agitation in Adults in the Intensive Care Unit
Psychomotor Agitation, Critical Illness
Not yet recruitingObservational study
Core Competencies in General Intensive Care Ultrasound (GenIUS): a Delphi Study
Critical Illness, Ultrasound
RecruitingObservational study
Predicting Extubation Failure Using Machine Learning
Extubation Failure, Critical Illness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah J Cook, MD principal investigator
McMaster University
67 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LMWH (Fragmin, dalteparin) and Unfractionated Heparin in people with Critical Illness and Deep Venous Thrombosis, run by McMaster University at 67 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 67 sites in Canada, Australia, Brazil, Saudi Arabia, United States and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00182143, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2011.