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.
The purpose of the study is to determine the effectiveness and safety of LMWH postoperative bridging therapy (standard of care) versus postoperative placebo bridging therapy (experimental arm)for patients with mechanical heart valves or atrial fibrillation or atrial flutter who are at high risk for stroke when warfarin is temporarily interrupted for a procedure.
|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 2015|
|Estimated Primary Completion Date:||March 2015 (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.
|Contact: Holly Van Spronsen, R.N.||519-685-8500 ext firstname.lastname@example.org|
|Contact: Michael Kovacs, MD||519-685-8500 ext email@example.com|
|Canada, Nova Scotia|
|QE II Health Sciences Centre||Recruiting|
|Halifax, Nova Scotia, Canada, B3H 2Y9|
|Contact: David Anderson, MD, FRCPC 902-473-8562 firstname.lastname@example.org|
|Contact: Rebekah Conlon, RN 902-473-7454 email@example.com|
|Principal Investigator: David Anderson|
|Hamilton Health Sciences Corporation-Henderson Site||Recruiting|
|Hamilton, Ontario, Canada, L8V 1C3|
|Contact: Clive Kearon, MD 905-527-4322 ext 42419 firstname.lastname@example.org|
|Contact: Tracy Winkworth, RN 905-527-4322 ext 43571 email@example.com|
|Principal Investigator: Clive Kearon|
|Hamilton Health Sciences Corporation-McMaster Site||Recruiting|
|Hamilton, Ontario, Canada, L8N 3Z5|
|Contact: Shannon Bates, MD 905-521-2100 ext 73928 firstname.lastname@example.org|
|Contact: Laurie Sardo, RN 905-521-2100 ext 76984 email@example.com|
|Principal Investigator: Shannon Bates|
|Hamilton Health Sciences Corporation-General Hospital||Recruiting|
|Hamilton, Ontario, Canada, L8L 2X2|
|Contact: Sam Schulman, MD 905-527-1710 ext 44810 firstname.lastname@example.org|
|Contact: Lisa Rudd-Scott, RN 905-527-4322 ext 44487 email@example.com|
|Principal Investigator: Sam Schulman|
|Ottawa Hospital-General Campus||Recruiting|
|Ottawa, Ontario, Canada, K1H 8L6|
|Contact: Marc A Rodger, MD, FRCPC 613-798-5555 ext 12694 firstname.lastname@example.org|
|Contact: Lynne Cullen, RN 613-798-5555 ext 17373 email@example.com|
|Principal Investigator: Marc Rodger|
|University Health Network - Toronto General Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2C4|
|Contact: Erik Yeo, MD, FRCP 416-340-4069 firstname.lastname@example.org|
|Contact: Sobia Hameed 416-340-4800 ext 8603 email@example.com|
|Principal Investigator: Erik Yeo|
|SMBD Jewish General Hospital||Recruiting|
|Montreal, Quebec, Canada, H3T 1E2|
|Contact: Mark Blostein, MD 514-340-8222 ext 3992 firstname.lastname@example.org|
|Contact: Viviane Pananis, RN 514-340-8222 ext 5982 email@example.com|
|Principal Investigator: Mark Blostein|
|Montreal General Hospital||Recruiting|
|Montreal, Quebec, Canada, H3G 1A4|
|Contact: Susan Solymoss, MD 514-934-1934 ext 42428 firstname.lastname@example.org|
|Contact: Barbara St.Jacques, RN 514-934-1934 ext 44198 email@example.com|
|Principal Investigator: Susan Solymoss|
|Hyderabad, Nampally, India, 500001|
|Contact: Guntuboina Rani, MCh 91-40 55517777 firstname.lastname@example.org|
|Contact: Mohammed Saleem 080-411206291 email@example.com|
|Principal Investigator: Guntubonia Rani|
|Sir Ganga Ram Hospital||Recruiting|
|New Delhi, India, 110060|
|Contact: Rajiv Passey, DM, DNB 9810178588 firstname.lastname@example.org|
|Contact: Mohammed Saleem 080-411206291 email@example.com|
|Principal Investigator: Rajiv Passey|
|Principal Investigator:||Michael J Kovacs, MD, FRCPC||University of Western Ontario, Canada|