PERIOP 2 - A Safety and Effectiveness of LMWH vs Placebo Bridging Therapy for Patients on Long Term Warfarin Requiring Temporary Interruption of Warfarin.
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| ClinicalTrials.gov Identifier: NCT00432796 |
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Recruitment Status :
Active, not recruiting
First Posted : February 8, 2007
Last Update Posted : February 19, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Stroke | Drug: Dalteparin Other: Placebo | Phase 3 |
There are a growing number of patients who receive long-term warfarin therapy for the prevention of arterial thromboembolism. The current approach to the perioperative management of anticoagulation (i.e. "bridging therapy") with low molecular weight heparin (LMWH) is not standardized and has not been assessed by adequate randomized studies. Most clinicians, however, recommend bridging therapy.
We have recently completed a multicentre single arm pilot study of LMWH bridging therapy. This study in 10 centres accrued 224 patients in 10 months. In the pilot study the postoperative thromboembolic event rate was 3.1% and 75% of these occurred in patients who had anticoagulation held due to bleeding.
Design:A prospective multicentre randomized double-blind controlled trial. Patients: Consecutive eligible and consenting patients from 11 teaching hospitals in Canada. A total of 1773 patients with prosthetic heart valves receiving long-term oral anticoagulation with warfarin or patients with atrial fibrillation/flutter and a major risk factor who require elective non-cardiac surgery or invasive procedure necessitating reversal of their oral anticoagulant therapy.
Treatment Schedule: Consent will be obtained preoperatively but randomization will be performed postoperatively after confirming eligibility.
Preoperative period: In all participants, warfarin therapy will be discontinued five days prior to the procedure. Dalteparin, a LMWH, will be administered at 200 IU/kg sc early in the morning for the three days prior to, but not including the day of, the procedure except on the day prior to surgery the dose will be 100 I.U./kg given 24 hours preoperatively. Warfarin will be resumed the evening of the procedure.
Postoperative period: Dalteparin or placebo will be administered daily (starting the morning after the procedure), provided surgical hemostasis is achieved, and will be continued for at least four days and until the INR is>2.0. Patients considered at high risk for a postoperative major bleed will be given dalteparin or placebo at a dose of 5,000 IU sc daily. Patients who undergo procedures that are considered low risk for bleeding complications will resume dalteparin or placebo at 200 IU/Kg s.c. daily.
Outcomes:The primary outcome will be the frequency of episodes of major thromboembolism over a 90-day follow-up period following the time of randomization. Secondary outcomes will include major bleeding and overall survival.
Relevance: To bridge or not to bridge, is a common clinical question, without randomized trial evidence to guide clinicians. This RCT will answer whether post-operative bridging reduces risk of thromboembolism or causes harm.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1473 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Prevention |
| Official Title: | A Double Blind Randomized Control Trial of Post-Operative Low Molecular Weight Heparin Bridging Therapy Versus Placebo Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism (PERIOP 2) |
| Study Start Date : | December 2006 |
| Actual Primary Completion Date : | March 2019 |
| Estimated Study Completion Date : | December 2020 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 1
patients are randomized post-operative to receive either active treatment or placebo. Active treatment is Dalteparin injectable. Patients randomized to active treatment will receive Dalteparin 5,000 iu or 200 iu/kg once daily depending on the type of surgery they have had. |
Drug: Dalteparin
5,000 iu or 200 iu/kg depending on the type of surgery injection will be given subcutaneously, once a day for a minimum of 4 days or until the INR is 2.0
Other Name: Fragmin |
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Experimental: 2
patients will be randomized post-operative to receive either active treatment or placebo
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Other: Placebo
patients will be randomized post-operative to receive either active treatment or placebo. the placebo will be given as a subcutaneous injection once a day. the amount of the placebo will be equivalent to the active treatment depending on the type of surgery. ie. 5,000 iu or 200 iu/kg |
- major thromboembolism [ Time Frame: 90 days from randomization ]
- major bleeding [ Time Frame: 90 days from randomization ]
- minor bleeding [ Time Frame: 90 days from randomization ]
- a composite of major bleeding and major thromboembolic events [ Time Frame: 90 days from randomization ]
- minor thromboembolic events [ Time Frame: 90 days from randomization ]
- overall survival. [ Time Frame: 90 days from randomization ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Informed consent,
- Patients aged >18
- Patients with prosthetic(mechanical) heart valve
- Patients with atrial fibrillation or atrial flutter and a major risk factor (previous TIA or stroke, high blood pressure, diabetes, aged >75, moderate/severe left ventricle dysfunction)
- Who are receiving long-term oral anticoagulation and require elective non-cardiac surgery or an invasive procedure with reversal of their anticoagulant therapy.
Exclusion Criteria:
- Evidence of active bleeding within last 30 days prior to stopping warfarin.
- Platelet count <100 x 109/L.
- Spinal or neurosurgery.
- Life expectancy less than 3 months.
- Calculated creatinine clearance <30 ml/min
- Patients requiring cardiac surgery.
- Multiple prosthetic(mechanical) valves or Starr-Edwards valve or prosthetic(mechanical) valve with a history of stroke or TIA
- History of heparin induced thrombocytopenia (HIT)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00432796
| Canada, Nova Scotia | |
| QE II Health Sciences Centre | |
| Halifax, Nova Scotia, Canada, B3H 2Y9 | |
| Canada, Ontario | |
| Hamilton Health Sciences Corporation-General Hospital | |
| Hamilton, Ontario, Canada, L8L 2X2 | |
| Hamilton Health Sciences Corporation-McMaster Site | |
| Hamilton, Ontario, Canada, L8N 3Z5 | |
| Hamilton Health Sciences Corporation-Henderson Site | |
| Hamilton, Ontario, Canada, L8V 1C3 | |
| Ottawa Hospital-General Campus | |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| Canada, Quebec | |
| SMBD Jewish General Hospital | |
| Montreal, Quebec, Canada, H3T 1E2 | |
| India | |
| Care Hospital | |
| Hyderabad, Nampally, India, 500001 | |
| Sir Ganga Ram Hospital | |
| New Delhi, India, 110060 | |
| Principal Investigator: | Michael J Kovacs, MD, FRCPC | University of Western Ontario, Canada |
| Responsible Party: | Michael Kovacs, M.D., Lawson Health Research Institute |
| ClinicalTrials.gov Identifier: | NCT00432796 |
| Other Study ID Numbers: |
R-06-267 NRA6300019 |
| First Posted: | February 8, 2007 Key Record Dates |
| Last Update Posted: | February 19, 2020 |
| Last Verified: | February 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Anticoagulation Prosthetic heart valves Atrial fibrillation Bridging Therapy |
Thromboembolism Warfarin Low Molecular Weight Heparin |
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Thromboembolism Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Dalteparin Tinzaparin |
Heparin, Low-Molecular-Weight Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |