Effects of Tinzaparin on Cardio-vascular Outcomes and on Blood Lipids in Diabetic Patients on Chronic Hemodialysis

December 21, 2017 updated by: Anemia Working Group Romania

Effects of Tinzaparin Sodium on Cardio-vascular OUtcomes and on Blood Lipids in Diabetic Patients on Chronic HEmodialysis: A Long-term, Prospective Study (The "Tinzaparin COULD HELP" Study).

Low molecular weight heparin (LMWH) provides a safe and effective alternative to UFH for hemodialysis anticoagulation. While unfractionated (UF) heparin has been implicated in hyper-lipidemia, the effect of LMWHs on the lipid profile in non-diabetic patients on chronic hemodialysis remains controversial. The effect of LMWH in diabetic patients, a high risk group for developing hyper-lipidemia and cardio-vascular disease, has not been studied.

The study intends to examine the long-term effects of the replacement of UFH by LMWH (tinzaparin sodium) on cardio-vascular outcomes and on lipoprotein profiles in a large group of diabetic patients stable on HD.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Hemodialysed diabetic patients constitute a high-risk subset of patients for developing cardio-vascular disease, which accounts for nearly 50% of deaths. In those patients, mortality rates probably exceed 20% per year. After stratification for age, race and gender, cardio-vascular mortality is 10-20 times higher in these patients than in the general population. Thus cardio-vascular risk factors in these patients should be managed early, aggressively and in a multi-factorial manner in order to reduce their high cardio-vascular morbidity and mortality.

Low molecular weight heparin (LMWH) provides a safe and effective alternative to UFH for hemodialysis anticoagulation. While unfractionated (UF) heparin has been implicated in hyper-lipidemia, the effect of LMWHs on the lipid profile in non-diabetic patients on chronic hemodialysis remains controversial. The effect of LMWH in diabetic patients, a high risk group for developing hyper-lipidemia and cardio-vascular disease, has not been studied.

The study intends to examine the long-term effects of the replacement of UFH by LMWH (tinzaparin sodium) on cardio-vascular outcomes and on lipoprotein profiles in a large group of diabetic patients stable on HD.

Tinzaparin sodium is superior to UFH in terms of reducing cardio-vascular and cerebrovascular outcomes (primary end-point). Tinzaparin sodium is superior to UFH in terms of reducing the specified lipid parameters of stable diabetic patients on chronic hemodialysis.

A time-to-event analysis is the tool that will be used for recording events rate. Accordingly, the study will aim in enrolling 200 diabetic nephropathy patients, but allowing for a 10% drop-out rate, the number of evaluable patients in the study will be 180.

Therefore, for the primary triple end-point of death/MI/stroke (ischemic) with 180 evaluable patients, we will have an 80% power (at a two-sided alpha level of 0.05) to detect a statistical significant difference in the 2 groups if the rate of events in the UFH group is 30% and on tinzaparin is 13% or less.

For the secondary end-points in cardiovascular morbidity and mortality, if we assume that the event rate in the UFH group is 50%, then a statistical significance can be achieved if the rate in the tinzaparin group is at 30% or less.

For differences in average lipid values between the 2 groups, with 180 evaluable patients, a 2-sided alpha level at 0.05 and with 80% power, we can detect statistical significance if the difference is: for Total Cholesterol=19 mg/dL (SD of 46), for HDL-C = 4.6 mg/dL (SD=11), for TG = 30 mg/dL (SD=72), for LDL-C = 15 (SD=36) and for ApoB = 13 (SD=32).

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Romania
      • Baia Mare, Romania
        • Baia Mare County Hospital
      • Brasov, Romania
        • "Sarah" Hemodialysis Centre
      • Bucharest, Romania
        • Fundeni Clinical Hospital
      • Bucharest, Romania, 010731
        • "Dr Carol Davila" Teaching Hospital of Nephrology
      • Bucharest, Romania
        • "N Paulescu" Institute
      • Cluj, Romania
        • Cluj University Hospital
      • Craiova, Romania
        • Dolj County Hospital
      • Focsani, Romania
        • Vrancea County Hospital
      • Iasi, Romania
        • "CI Parhon" Clinical Hospital
      • Oradea, Romania
        • Bihor County Hospital
      • Ploiesti, Romania
        • Prahova County Hospital
      • Targoviste, Romania
        • Dambovita County Hospital
      • Timisoara, Romania
        • Timisoara County Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • willingness to give written informed consent for participation in the study
  • age 18-80 years old
  • ability to understand and follow instructions and able to participate in the study for the entire period
  • clinically stable (based on the investigator's judgment) within the three months prior to the screening visit
  • written and signed agreement

Exclusion Criteria:

  • antecedents of cerebrovascular accident, documented myocardial infarction, coronary angioplasty or bypass surgery within 6 months prior to the screening visit
  • currently enrollment in any other investigational device or drug study, or participation in another clinical study within 30 days prior to the screening visit
  • known or suspected drug or alcohol abuse
  • known congenital or acquired bleeding disorders including hepatic failure and amyloidosis, present active major bleeding;
  • increased risk of hemorrhage, due to: pericarditis or bacterial endocarditis, severe uncontrolled hypertension, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, shortly after brain, spinal or ophthalmological surgery, concomitant treatment with platelet inhibitors, recent surgical procedures (especially with hemorrhagic complications or those in which hemorrhagic complications would be very severe - cardio-vascular, ophthalmological or neurological), planned surgical procedure within the next week, (history of) heparin-induced thrombocytopenia, with any other disease which, in the opinion of the investigator, makes unacceptable his/her inclusion in the study (known hypersensitivity to heparin, benzyl alcohol, or pork products that should not be treated with innohep®, severe psychiatric disorders, age <18 years, malignant disorders and a life expectancy <6 months, patients that were involved in another research study (studies) in the last month.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tinzaparin
Patients will receive Tinzaparin as anticoagulant during the HD session.
Drug: Tinzaparin administration
Patients will receive tinzaparin during the HD session
Active Comparator: Heparin
Patients will receive Heparin as an anticoagulant during the HD session
Drug: Heparin administration
Patients will receive Heparin as an anticoagulant during the HD session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
the composite event rate in death (any cause), myocardial infarction and stroke

Secondary Outcome Measures

Outcome Measure
Lipid profile
Cardio-vascular: the composite event rate of unstable angina, transient ischemic attacks, peripheral arterial disease, other, consequent to atherosclerosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anemia Working Group Romania

Investigators

  • Study Chair: Gabriel Mircescu, Professor, Dr Carol Davila Teaching Hospital of Nephrology
  • Study Director: Constantin Verzan, MD, PhD, "Dr Carol Davila" Teaching Hospital of Neprology
  • Principal Investigator: Cristina Capusa, MD, PhD, Dr Carol Davila Teaching Hospital of Nephrology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2009

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

December 4, 2006

First Submitted That Met QC Criteria

December 4, 2006

First Posted (Estimate)

December 5, 2006

Study Record Updates

Last Update Posted (Actual)

December 22, 2017

Last Update Submitted That Met QC Criteria

December 21, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06_06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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