A Comparison of Dalteparin and Tinzaparin for Prevention of Blood Clots in Hemodialysis Patients on Oral Anticoagulants Having Surgery

Tinzaparin Versus Dalteparin for Perioperative Thromboembolic Prophylaxis in Patients With Dialysis Dependent Renal Disease- A Canadian Multicentre Trial

The purpose of this study is to better understand if either dalteparin or tinzaparin is a better drug to use in dialysis patients on blood thinners who are at high risk of developing blood clots and need surgery.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; Thromboembolism
• Intervention / Treatment: Drug: Fragmin (dalteparin); Drug: Innohep (tinzaparin)

Detailed Description

A prospective multicenter randomised trial involving 60 consecutive eligible and consenting patients from teaching hospitals in Canada. Patients will be randomised to either tinzaparin or dalteparin to investigate the pharmacokinetics of both low molecular weight heparins (LMWH) perioperatively in a special population, namely end stage renal disease (ESRD) dialysis patients.

To date although there exists evidence to suggest tinzaparin may be safe in patients on hemodialysis, LMWHs as a group have not been investigated in the perioperative setting in these patients. This protocol has been developed so that the pharmacokinetic behaviour of tinzaparin and dalteparin can be compared but also so that the duration off warfarin is minimised. Therapeutic doses of LMWH are administered pre-procedure during as much time of the period as possible that oral anticoagulation is sub-therapeutic.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N4A6
      • St. Joseph's Healthcare
    • Ottawa, Ontario, Canada, K1Y4E9
      • The Ottawa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent
• Patients aged >= 18 with end stage renal disease requiring chronic hemodialysis (HD) three times a week and clinically stable on HD for 4 weeks (x 4 wks)
• Patients requiring active oral anticoagulation for prosthetic heart valves, recent deep vein thrombosis >= 1 month, or patients with atrial fibrillation and a major risk factor (previous transient ischemic attack [TIA] or stroke, high blood pressure, diabetes, aged >= 75, moderate/severe left ventricle dysfunction) who require elective non-cardiac surgery or an invasive procedure with reversal of their anticoagulant therapy.

Exclusion Criteria:

• Evidence of active bleeding prior to stopping warfarin
• Hemoglobin <= 90 or platelet count <= 100x10^9/L
• Uncontrolled hypertension or stroke within 6 months of study commencement
• Spinal or neurosurgery
• Eye surgery (excluding cataract surgery)
• Life expectancy less than 3 months
• Patients requiring cardiac surgery
• Presence of active duodenal ulcer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Dalteparin; Dalteparin 200 IU/kg/day for three days prior to surgery and dalteparin 5000IU daily for 3-5 days post-surgery	Drug: Fragmin (dalteparin); 200 IU/Kg/Day administered subcutaneously for three days prior to but not including the day of the surgery
ACTIVE_COMPARATOR: Tinzaparin; Tinzaparin 175 IU/kg/day for three days prior to surgery and Tinzaparin 4500 IU for 3-5 days post surgery	Drug: Innohep (tinzaparin); 175 IU/kg/Day administered subcutaneously for three days prior to but not including the day of the surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome will be the comparison of the pharmacokinetic profiles of dalteparin and tinzaparin in patients on hemodialysis in the setting of perioperative anticoagulation for thromboembolic prophylaxis. Specifically pre-dialysis anti-Xa levels post	Anti-Xa levels were drawn pre-dialysis (at a timepoint that was within 20-24hrs post- LMWH dose) and post- dialysis	Pre-dialysis following the third dose of LMWH

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The frequency of surgery cancellation	We will collect data on reasons why surgeries were cancelled in this patient population	Cumulatively collected at end of study
Bleeding complications		Any reported and elicited bleeding event will be captured throughout the study period

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: LEO Pharma
• Investigators: Principal Investigator: Marc Rodger, MD, MSc, OHRI

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): November 1, 2008

Study Registration Dates

• First Submitted: November 30, 2005
• First Submitted That Met QC Criteria: November 30, 2005
• First Posted (ESTIMATE): December 2, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): September 10, 2014
• Last Update Submitted That Met QC Criteria: September 8, 2014
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Pharmacokinetics; End stage renal disease; warfarin; Prophylaxis; Hemodialysis; Oral anticoagulation; INR; Coumadin; Low Molecular Weight Heparin; Tinzaparin; Thromboembolic disease; Dalteparin; Innohep; Fragmin; Anti Xa
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: 2003391-01H