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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Thromboembolism, Hemodialysis

Intervention / Treatment
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* Drug: Fragmin (dalteparin)
* Drug: Innohep (tinzaparin)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylaxis, Thromboembolic disease, End stage renal disease, Hemodialysis, Pharmacokinetics, Low Molecular Weight Heparin, Innohep, Tinzaparin, Fragmin, Dalteparin, Anti Xa, INR, Oral anticoagulation, warfarin, Coumadin