Diabetes MellitusPhase 4NCT00407641
Effects of Tinzaparin on Cardio-vascular Outcomes and on Blood Lipids in Diabetic Patients on Chronic Hemodialysis
A Phase 4 study testing Tinzaparin administration and Heparin administration in people with Diabetes Mellitus and Hemodialysis, run by Anemia Working Group Romania at 13 sites in Romania.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetes Mellitus, Hemodialysis
- What is being tested?
- Tinzaparin administration and Heparin administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 13 sitesRomania
- Study dates
- Mar 2009to Jan 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Romania13 sites
Baia Mare County Hospital
Baia Mare
"Sarah" Hemodialysis Centre
Brasov
"Dr Carol Davila" Teaching Hospital of Nephrology
Bucharest, 010731
"N Paulescu" Institute
Bucharest
Fundeni Clinical Hospital
Bucharest
Cluj University Hospital
Cluj-Napoca
Dolj County Hospital
Craiova
Vrancea County Hospital
Focşani
"CI Parhon" Clinical Hospital
Iași
Bihor County Hospital
Oradea
Prahova County Hospital
Ploieşti
Dambovita County Hospital
Targoviste
Timisoara County Hospital
Timișoara
About this study
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).
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.
Read the 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).
- Conditions
- Diabetes Mellitus, Hemodialysis
- Being tested
- Tinzaparin administration, Heparin administration
- Keywords
- diabetes mellitus, chronic hemodialysis, anticoagulation, outcome
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tinzaparin administrationDrug
Patients will receive tinzaparin during the HD session
Heparin administrationDrug
Patients will receive Heparin as an anticoagulant during the HD session.
| Study group | Role | What they receive |
|---|---|---|
| Tinzaparin | Experimental | Patients will receive Tinzaparin as anticoagulant during the HD session. Receives: Drug: Tinzaparin administration |
| Heparin | Active comparator | Patients will receive Heparin as an anticoagulant during the HD session Receives: Drug: Heparin administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
the composite event rate in death (any cause), myocardial infarction and stroke
Secondary outcomes (2)
Cardio-vascular: the composite event rate of unstable angina, transient ischemic attacks, peripheral arterial disease, other, consequent to atherosclerosis
Lipid profile
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2006 (estimated)
- Study startMar 2009
- Primary completionJan 2015
- Study completionJan 2017
Why it stopped: Financial and administrative matters did not allow collaboration among centers.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anemia Working Group Romania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gabriel Mircescu, Professor, Study chair, Dr Carol Davila Teaching Hospital of NephrologyConstantin Verzan, MD, PhD, Study director, "Dr Carol Davila" Teaching Hospital of NeprologyCristina Capusa, MD, PhD, Principal investigator, Dr Carol Davila Teaching Hospital of Nephrology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00407641
- Sponsor's protocol ID
- 06_06
- Status last verified
- Jan 2017
- First submitted
- 4 Dec 2006
- Last updated
- 22 Dec 2017
- Results posted
- No
Publications
Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.
PubMed 38189593
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT00407641
- Acronym / sponsor ID
- 06_06
- Conditions
- Diabetes Mellitus, Hemodialysis
- Keywords
- diabetes mellitus, chronic hemodialysis, anticoagulation, outcome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Financial and administrative matters did not allow collaboration among centers.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Anemia Working Group RomaniaUniversity, hospital or other
- Study start
- Mar 2009 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 5 Dec 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tinzaparin | Experimental | Drug: Tinzaparin administrationPatients will receive Tinzaparin as anticoagulant during the HD session. |
| Heparin | Active comparator | Drug: Heparin administrationPatients will receive Heparin as an anticoagulant during the HD session |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tinzaparin administrationPatients will receive tinzaparin during the HD session | Drug | Tinzaparin |
| Heparin administrationPatients will receive Heparin as an anticoagulant during the HD session. | Drug | Heparin |
Primary outcome
the composite event rate in death (any cause), myocardial infarction and stroke
2 secondary outcomes
Cardio-vascular: the composite event rate of unstable angina, transient ischemic attacks, peripheral arterial disease, other, consequent to atherosclerosis
Lipid profile
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2017.
- Derived from this study: PubMed 38189593Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriel Mircescu, Professor study chair
Dr Carol Davila Teaching Hospital of Nephrology
Constantin Verzan, MD, PhD study director
"Dr Carol Davila" Teaching Hospital of Neprology
Cristina Capusa, MD, PhD principal investigator
Dr Carol Davila Teaching Hospital of Nephrology
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tinzaparin administration and Heparin administration in people with Diabetes Mellitus and Hemodialysis, run by Anemia Working Group Romania at 13 sites in Romania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the composite event rate in death (any cause), myocardial infarction and stroke. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00407641, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2017.