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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.

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Pfizer
Information provided by (Responsible Party):
Michael Kovacs, Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT00432796
First received: February 7, 2007
Last updated: March 2, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Stroke
Drug: Dalteparin
Other: Placebo
Phase 3

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:
  • major thromboembolism [ Time Frame: 90 days from randomization ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 1473
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)
Arms Assigned Interventions
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
Experimental: 2
patients will be randomized post-operative to receive either active treatment or placebo
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


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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00432796

Locations
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
Sponsors and Collaborators
Lawson Health Research Institute
Canadian Institutes of Health Research (CIHR)
Pfizer
Investigators
Principal Investigator: Michael J Kovacs, MD, FRCPC University of Western Ontario, Canada
  More Information

Publications:
POLLER L, THOMSON J. EVIDENCE FOR

Responsible Party: Michael Kovacs, M.D., Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT00432796     History of Changes
Other Study ID Numbers: R-06-267  NRA6300019 
Study First Received: February 7, 2007
Last Updated: March 2, 2016
Health Authority: Canada: Health Canada

Keywords provided by Lawson Health Research Institute:
Anticoagulation
Prosthetic heart valves
Atrial fibrillation
Bridging Therapy
Thromboembolism
Warfarin
Low Molecular Weight Heparin

Additional relevant MeSH terms:
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Heparin
Warfarin
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016