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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.

Information source: Lawson Health Research Institute
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Stroke

Intervention: Dalteparin (Drug); Placebo (Other)

Phase: Phase 3

Status: Recruiting

Sponsored by: Lawson Health Research Institute

Official(s) and/or principal investigator(s):
Michael J Kovacs, MD, FRCPC, Principal Investigator, Affiliation: University of Western Ontario, Canada

Overall contact:
Luljeta(Luli) Pallaveshi, RN,LLB, BA, Phone: 519-685-8500, Ext: 55148, Email: Luli.Pallaveshi@sjhc.london.on.ca

Summary

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: major thromboembolism

Secondary outcome:

major bleeding

minor bleeding

a composite of major bleeding and major thromboembolic events

minor thromboembolic events

overall survival.

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Informed consent, 2. Patients aged >18 3. Patients with prosthetic(mechanical) heart valve 4. 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) 5. 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: 1. Evidence of active bleeding within last 30 days prior to stopping warfarin. 2. Platelet count <100 x 109/L. 3. Spinal or neurosurgery. 4. Life expectancy less than 3 months. 5. Calculated creatinine clearance <30 ml/min 6. Patients requiring cardiac surgery. 7. Multiple prosthetic(mechanical) valves or Starr-Edwards valve or prosthetic(mechanical) valve with a history of stroke or TIA 8. History of heparin induced thrombocytopenia (HIT)

Locations and Contacts

Luljeta(Luli) Pallaveshi, RN,LLB, BA, Phone: 519-685-8500, Ext: 55148, Email: Luli.Pallaveshi@sjhc.london.on.ca

Sir Ganga Ram Hospital, New Delhi 110060, India; Recruiting
Rajiv Passey, DM, DNB, Phone: 9810178588, Email: drrpassey@yahoo.com
Mohammed Saleem, Phone: 080-411206291, Email: mdsaleem@iprocess.net
Rajiv Passey, Principal Investigator

Care Hospital, Hyderabad, Nampally 500001, India; Recruiting
Guntuboina Rani, MCh, Phone: 91-40 55517777, Email: ushatangana@yahoo.com
Mohammed Saleem, Phone: 080-411206291, Email: mdsaleem@iprocess.net
Guntubonia Rani, Principal Investigator

QE II Health Sciences Centre, Halifax, Nova Scotia B3H 2Y9, Canada; Recruiting
David Anderson, MD, FRCPC, Phone: 902-473-8562, Email: david.anderson@cdha.nshealth.ca
Rebekah Conlon, RN, Phone: 902-473-7454, Email: rebekah.conlon@cdha.nshealth.ca
David Anderson, Principal Investigator

Hamilton Health Sciences Corporation-General Hospital, Hamilton, Ontario L8L 2X2, Canada; Recruiting
Sam Schulman, MD, Phone: 905-527-1710, Ext: 44810, Email: schuls@mcmaster.ca
Lisa Rudd-Scott, RN, Phone: 905-527-4322, Ext: 44487, Email: ruddl@hhsc.ca
Sam Schulman, Principal Investigator

Hamilton Health Sciences Corporation-Henderson Site, Hamilton, Ontario L8V 1C3, Canada; Recruiting
Clive Kearon, MD, Phone: 905-527-4322, Ext: 42419, Email: kearonc@mcmaster.ca
Tracy Winkworth, RN, Phone: 905-527-4322, Ext: 43571, Email: winkwot@mcmaster.ca
Clive Kearon, Principal Investigator

Hamilton Health Sciences Corporation-McMaster Site, Hamilton, Ontario L8N 3Z5, Canada; Recruiting
Shannon Bates, MD, Phone: 905-521-2100, Ext: 73928, Email: bates@mcmaster.ca
Laurie Sardo, RN, Phone: 905-521-2100, Ext: 76984, Email: sardola@hhsc.ca
Shannon Bates, Principal Investigator

Ottawa Hospital-General Campus, Ottawa, Ontario K1H 8L6, Canada; Recruiting
Marc A Rodger, MD, FRCPC, Phone: 613-798-5555, Ext: 12694, Email: mrodger@ohri.ca
Lynne Cullen, RN, Phone: 613-798-5555, Ext: 17373, Email: lycullen@ohri.ca
Marc Rodger, Principal Investigator

SMBD Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada; Recruiting
Mark Blostein, MD, Phone: 514-340-8222, Ext: 3992, Email: mark.blostein@mcgill.ca
Viviane Pananis, RN, Phone: 514-340-8222, Ext: 5982, Email: vpananis@gmail.com
Mark Blostein, Principal Investigator

Additional Information

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Starting date: December 2006
Last updated: April 8, 2015

Page last updated: August 20, 2015

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