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

This study has suspended participant recruitment.
(Financial and administrative matters did not allow collaboration among centers.)
Sponsor:
Information provided by:
Anemia Working Group Romania
ClinicalTrials.gov Identifier:
NCT00407641
First received: December 4, 2006
Last updated: January 26, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Hemodialysis
Drug: Tinzaparin administration
Drug: Heparin administration
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Anemia Working Group Romania:

Primary Outcome Measures:
  • the composite event rate in death (any cause), myocardial infarction and stroke

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

Estimated Enrollment: 200
Study Start Date: March 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00407641

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

No publications provided

Responsible Party: Gabriel Mircescu, Anemia Working Group Romania
ClinicalTrials.gov Identifier: NCT00407641     History of Changes
Other Study ID Numbers: 06_06
Study First Received: December 4, 2006
Last Updated: January 26, 2013
Health Authority: Romania: National Medicines Agency

Keywords provided by Anemia Working Group Romania:
diabetes mellitus
chronic hemodialysis
anticoagulation
outcome

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Calcium heparin
Anticoagulants
Heparin
Tinzaparin
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 17, 2014