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

Sponsor

Anemia Working Group Romania (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00407641

Collaborator

(none)

Enrollment

Locations

Arms

94.1

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Hemodialysis	Drug: Tinzaparin administration Drug: Heparin administration	Phase 4

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.

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

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).

Actual Study Start Date :

Mar 1, 2009

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2017

Arms and Interventions

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.

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.

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Baia Mare County Hospital	Baia Mare	Romania
2	"Sarah" Hemodialysis Centre	Brasov	Romania
3	"Dr Carol Davila" Teaching Hospital of Nephrology	Bucharest	Romania	010731
4	"N Paulescu" Institute	Bucharest	Romania
5	Fundeni Clinical Hospital	Bucharest	Romania
6	Cluj University Hospital	Cluj	Romania
7	Dolj County Hospital	Craiova	Romania
8	Vrancea County Hospital	Focsani	Romania
9	"CI Parhon" Clinical Hospital	Iasi	Romania
10	Bihor County Hospital	Oradea	Romania
11	Prahova County Hospital	Ploiesti	Romania
12	Dambovita County Hospital	Targoviste	Romania
13	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