PERIOP 2 - A Safety and Effectiveness Study of LMWH Bridging Therapy Versus Placebo Bridging Therapy for Patients on Long Term Warfarin and Require Temporary Interruption of Their Warfarin.
|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:||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)|
- major thromboembolism [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]
- major bleeding [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]
- minor bleeding [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]
- a composite of major bleeding and major thromboembolic events [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]
- minor thromboembolic events [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]
- overall survival. [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2006|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
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.
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
patients will be randomized post-operative to receive either active treatment or 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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00432796
|Canada, Nova Scotia|
|QE II Health Sciences Centre|
|Halifax, Nova Scotia, Canada, B3H 2Y9|
|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|
|SMBD Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|
|Hyderabad, Nampally, India, 500001|
|Sir Ganga Ram Hospital|
|New Delhi, India, 110060|
|Principal Investigator:||Michael J Kovacs, MD, FRCPC||University of Western Ontario, Canada|