Venous ThrombosisNCT00186745
Use of Low Molecular Weight Heparin (Tinzaparin) to Treat Blood Clots in Patients With Kidney Failure
A study testing Tinzaparin in people with Venous Thrombosis and Pulmonary Embolism, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
Trial summary
Blood clots in the leg veins, known as deep vein thrombosis, are important because they may travel to the lung (known as pulmonary embolism) and cause death. Blood clots are treated with blood thinners, or anticoagulants. The preferred treatment is an anticoagulant known as low molecular weight heparin (LMWH). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Venous Thrombosis, Pulmonary Embolism
- What is being tested?
- Tinzaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2005to Feb 2016
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients 18 years of age or older
- Objectively confirmed VTE requiring anticoagulant therapy, including lower extremity and upper extremity deep vein thrombosis (catheter and non-catheter related, including dialysis access thrombosis [i.e., graft, fistula]); peripheral vein thrombosis (e.g., portal vein, mesenteric vein, cerebral vein thrombosis), and pulmonary embolism
Who cannot join
- Weight exceeding 105 kg
- Unstable declining renal function, defined as documented change in creatinine > 20% in the past 3 months or clinical circumstances likely to be associated with change in renal function, such as dehydration or severe intercurrent illness. Where no previous creatinine values exist and the patient is otherwise stable, patients will not be excluded on the basis of unknown previous renal function.
- Known allergy to heparin/LMWHs or history of heparin induced thrombocytopenia
- Treatment with UFH, LMWH, danaparoid, oral direct thrombin inhibitors for >48 h
- Bleeding requiring hospitalization or blood transfusion within 6 months(exception is blood transfusion given in relation to surgical procedures within 6 months)
- History of intracerebral hemorrhage
Show all 13Show fewer
- Known active liver disease (AST or ALT > 3 times the upper limit of normal, or bilirubin > 50 umol/L)
- Known active peptic ulcer disease, with ongoing symptoms or need for anti-ulcer medical therapy
- Thrombocytopenia (platelet count of < 100 x 109/L)
- Ongoing need for antiplatelet agents (clopidogrel, ticlopidine, aspirin > 325 mg daily)
- Pregnancy or lactation
- Geographic inaccessibility
- Unable, or unwilling, to provide written informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Tinzaparin for Treatment of Venous Thromboembolism in Renal Insufficiency: A Pilot Study
Blood clots in the leg veins, known as deep vein thrombosis, are important because they may travel to the lung (known as pulmonary embolism) and cause death. Blood clots are treated with blood thinners, or anticoagulants. The preferred treatment is an anticoagulant known as low molecular weight heparin (LMWH). LMWH is given by an injection under the skin, which is convenient for patients because they can self-administer this medication at home, and no blood testing is required. However, LMWH is cleared from the body through the kidneys, so patients who have kidney failure are generally not treated with LMWH because they may be at a higher risk of bleeding.
One type of LMWH, known as tinzaparin, may be less dependent on the kidneys for clearance and may not increase in patients with kidney failure. The investigators would like to use tinzaparin to treat patients who have deep vein thrombosis or pulmonary embolism, and who also have kidney failure.
The purpose of this study is to determine whether the blood thinning effects of tinzaparin build up, or accumulate, in patients with varying degrees of kidney failure compared to patients without kidney failure. The blood thinning effects will be measured using a blood test known as an anti-Xa level. Patients will be followed over the time they receive tinzaparin and those patients who are found to have potentially high levels of tinzaparin (based on the anti-Xa level) will have their tinzaparin dose adjusted. The investigators believe that the levels of tinzaparin will not accumulate to potentially dangerous levels in a significant number of patients with kidney failure.
Read the detailed description
Background and rationale. Venous thromboembolism (VTE) is an important clinical problem because it is common, preventable, contributes to morbidity and mortality, and is costly. Low molecular weight heparin (LMWH) is the preferred anticoagulant for VTE treatment, but is renally excreted. Consequently, LMWH use in patients with renal insufficiency may result in accumulation of the anticoagulant effects and the potential for avoidable bleeding complications. As a result, most patients with renal insufficiency who also have VTE are unable to benefit from LMWH treatment. These patients are therefore generally treated in hospital using unfractionated heparin (UFH), since it is eliminated by extra-renal mechanisms. In addition to those patients with known renal insufficiency, many elderly patients have previously unrecognized renal insufficiency and treatment of these patients with LMWH can be associated with accumulation of the anticoagulant effect and avoidable bleeding.
Tinzaparin, relative to other LMWHs, has a higher molecular weight and greater negative charge: both biochemical features that favour non-renal clearance. There is limited evidence to support the hypothesis that tinzaparin, unlike other LMWHs, does not accumulate in patients with renal insufficiency. 1) Observational studies demonstrated no increase in anti-Xa levels (i.e., no accumulation) when tinzaparin was used for VTE treatment in elderly patients with renal insufficiency. 2) One study showed undetectable LMWH anticoagulant activity by 24 hours after dosing in hemodialysis patients. 3) A systematic review and meta-analysis of the literature in this area performed by our research group found no difference in bleeding and thrombosis complication rates when LMWH (compared to UFH) was used to maintain dialysis circuit patency in patients on hemodialysis.
The current factors which limit the use of tinzaparin in the treatment of patients with VTE and renal insufficiency are: 1) the true risk of accumulation is unknown in a spectrum of patients with varying renal function, and 2) the bleeding risk associated with tinzaparin use is unknown.
Hypothesis. We hypothesize that accumulation during a 5-day course of tinzaparin will not be related to the degree of renal insufficiency.
Study design and methods. We will perform a prospective cohort study of 200 patients with acute VTE, stratified into 4 equal-sized groups by renal function, who will receive initial anticoagulation with tinzaparin for 5 days concurrent with oral anticoagulants. The LMWH anticoagulant effect will be assessed at days 3 and 5 (+/- 1) using trough anti-Xa heparin levels. If accumulation occurs, defined as a trough anti-Xa level > 0.5 IU/mL, the tinzaparin dose will be adjusted according to a nomogram. Patients with an anti-Xa level ≤ 0.5 IU/mL will have no dose adjustment; patients with levels > 0.5 IU/mL will have their tinzaparin dose reduced.
The primary outcome of this study is the proportion of patients in each renal function group with accumulation on or before day 5. We will follow the patients for 48 hours after their final tinzaparin injection. Secondary outcomes are bleeding, recurrent thrombosis, accumulation by day 3, and trough anti-Xa levels > 1.0 IU/mL at any point in the study.
Significance. We hypothesize that tinzaparin does not accumulate in patients with renal insufficiency. However, if accumulation occurs, we hypothesize that dose adjustment according to our novel nomogram will prevent potentially-dangerous levels occurring by day 5. In either case, we will be able to proceed to the next stage in our research plan: an application for funding for a large simple randomized controlled trial examining the safety and efficacy of tinzaparin compared with UFH in patients with renal insufficiency. If accumulation occurs despite the use of the nomogram, then this surrogate outcome suggests that the use of therapeutic-dose tinzaparin is unlikely to be safe in patients with renal insufficiency, a finding which will limit the need to expend further resources on this line of research.
- Conditions
- Venous Thrombosis, Pulmonary Embolism
- Being tested
- Tinzaparin
- Keywords
- Venous thrombosis, Pulmonary embolism, Kidney failure, Anticoagulants, Heparin, Low-Molecular-Weight
- Medical subject headings
- Venous Thrombosis, Pulmonary Embolism, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TinzaparinDrug
Also called Brand name: Innohep
Dose: 175 IU/kg subcutaneously once daily, up to 7 days. Dose reduction as per protocol if anti-Xa levels exceed pre-defined limits.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | All patients in this cohort receive treatment with weight-adjusted, standard-dose tinzaparin for treatment of venous thromboembolism. Trough anti-Xa level measurements done on any 2 of days 3, 5 or 7 of treatment. Patients with a trough anti-Xa level > 0.5 IU/mL receive dose adjustment of the tinzaparin. Receives: Drug: Tinzaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-Xa level measured on any two of Days 3, 5 or 7 of treatment
Measured: Up to 7 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startMar 2005
- Primary completionNov 2015
- Study completionFeb 2016
Why it stopped: Funding ceased
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Venous ThrombosisStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Healthcare Hamilton
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario, LEO Pharma
- Responsible party
- Principal investigator, Wendy Lim, St. Joseph's Healthcare Hamilton
- Investigators
- Wendy Lim, MD, Principal investigator, St Joseph's Healthcare Hamilton / McMaster UniversityMark A Crowther, MD, Principal investigator, St Joseph's Healthcare Hamilton / McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00186745
- Sponsor's protocol ID
- NA 5723
- Status last verified
- Apr 2016
- First submitted
- 13 Sep 2005
- Last updated
- 19 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tinzaparin for Treatment of Venous Thromboembolism in Renal Insufficiency: A Pilot Study
- ClinicalTrials.gov ID
- NCT00186745
- Acronym / sponsor ID
- NA 5723
- Conditions
- Venous Thrombosis, Pulmonary Embolism
- Keywords
- Venous thrombosis, Pulmonary embolism, Kidney failure, Anticoagulants, Heparin, Low-Molecular-Weight
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding ceased
- Enrolment
- 148 participants (actual)
- Lead sponsor
- St. Joseph's Healthcare HamiltonUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario, LEO Pharma
- Study start
- Mar 2005
- Primary completion
- Nov 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 16 Sep 2005 (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.
Blood clots in the leg veins, known as deep vein thrombosis, are important because they may travel to the lung (known as pulmonary embolism) and cause death. Blood clots are treated with blood thinners, or anticoagulants. The preferred treatment is an anticoagulant known as low molecular weight heparin (LMWH). LMWH is given by an injection under the skin, which is convenient for patients because they can self-administer this medication at home, and no blood testing is required. However, LMWH is cleared from the body through the kidneys, so patients who have kidney failure are generally not treated with LMWH because they may be at a higher risk of bleeding.
One type of LMWH, known as tinzaparin, may be less dependent on the kidneys for clearance and may not increase in patients with kidney failure. The investigators would like to use tinzaparin to treat patients who have deep vein thrombosis or pulmonary embolism, and who also have kidney failure.
The purpose of this study is to determine whether the blood thinning effects of tinzaparin build up, or accumulate, in patients with varying degrees of kidney failure compared to patients without kidney failure. The blood thinning effects will be measured using a blood test known as an anti-Xa level. Patients will be followed over the time they receive tinzaparin and those patients who are found to have potentially high levels of tinzaparin (based on the anti-Xa level) will have their tinzaparin dose adjusted. The investigators believe that the levels of tinzaparin will not accumulate to potentially dangerous levels in a significant number of patients with kidney failure.
Detailed description
Background and rationale. Venous thromboembolism (VTE) is an important clinical problem because it is common, preventable, contributes to morbidity and mortality, and is costly. Low molecular weight heparin (LMWH) is the preferred anticoagulant for VTE treatment, but is renally excreted. Consequently, LMWH use in patients with renal insufficiency may result in accumulation of the anticoagulant effects and the potential for avoidable bleeding complications. As a result, most patients with renal insufficiency who also have VTE are unable to benefit from LMWH treatment. These patients are therefore generally treated in hospital using unfractionated heparin (UFH), since it is eliminated by extra-renal mechanisms. In addition to those patients with known renal insufficiency, many elderly patients have previously unrecognized renal insufficiency and treatment of these patients with LMWH can be associated with accumulation of the anticoagulant effect and avoidable bleeding.
Tinzaparin, relative to other LMWHs, has a higher molecular weight and greater negative charge: both biochemical features that favour non-renal clearance. There is limited evidence to support the hypothesis that tinzaparin, unlike other LMWHs, does not accumulate in patients with renal insufficiency. 1) Observational studies demonstrated no increase in anti-Xa levels (i.e., no accumulation) when tinzaparin was used for VTE treatment in elderly patients with renal insufficiency. 2) One study showed undetectable LMWH anticoagulant activity by 24 hours after dosing in hemodialysis patients. 3) A systematic review and meta-analysis of the literature in this area performed by our research group found no difference in bleeding and thrombosis complication rates when LMWH (compared to UFH) was used to maintain dialysis circuit patency in patients on hemodialysis.
The current factors which limit the use of tinzaparin in the treatment of patients with VTE and renal insufficiency are: 1) the true risk of accumulation is unknown in a spectrum of patients with varying renal function, and 2) the bleeding risk associated with tinzaparin use is unknown.
Hypothesis. We hypothesize that accumulation during a 5-day course of tinzaparin will not be related to the degree of renal insufficiency.
Study design and methods. We will perform a prospective cohort study of 200 patients with acute VTE, stratified into 4 equal-sized groups by renal function, who will receive initial anticoagulation with tinzaparin for 5 days concurrent with oral anticoagulants. The LMWH anticoagulant effect will be assessed at days 3 and 5 (+/- 1) using trough anti-Xa heparin levels. If accumulation occurs, defined as a trough anti-Xa level > 0.5 IU/mL, the tinzaparin dose will be adjusted according to a nomogram. Patients with an anti-Xa level ≤ 0.5 IU/mL will have no dose adjustment; patients with levels > 0.5 IU/mL will have their tinzaparin dose reduced.
The primary outcome of this study is the proportion of patients in each renal function group with accumulation on or before day 5. We will follow the patients for 48 hours after their final tinzaparin injection. Secondary outcomes are bleeding, recurrent thrombosis, accumulation by day 3, and trough anti-Xa levels > 1.0 IU/mL at any point in the study.
Significance. We hypothesize that tinzaparin does not accumulate in patients with renal insufficiency. However, if accumulation occurs, we hypothesize that dose adjustment according to our novel nomogram will prevent potentially-dangerous levels occurring by day 5. In either case, we will be able to proceed to the next stage in our research plan: an application for funding for a large simple randomized controlled trial examining the safety and efficacy of tinzaparin compared with UFH in patients with renal insufficiency. If accumulation occurs despite the use of the nomogram, then this surrogate outcome suggests that the use of therapeutic-dose tinzaparin is unlikely to be safe in patients with renal insufficiency, a finding which will limit the need to expend further resources on this line of research.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: TinzaparinAll patients in this cohort receive treatment with weight-adjusted, standard-dose tinzaparin for treatment of venous thromboembolism. Trough anti-Xa level measurements done on any 2 of days 3, 5 or 7 of treatment. Patients with a trough anti-Xa level > 0.5 IU/mL receive dose adjustment of the tinzaparin. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult patients 18 years of age or older
- Objectively confirmed VTE requiring anticoagulant therapy, including lower extremity and upper extremity deep vein thrombosis (catheter and non-catheter related, including dialysis access thrombosis [i.e., graft, fistula]); peripheral vein thrombosis (e.g., portal vein, mesenteric vein, cerebral vein thrombosis), and pulmonary embolism
Key exclusion criteria (13 listed)
- Weight exceeding 105 kg
- Unstable declining renal function, defined as documented change in creatinine > 20% in the past 3 months or clinical circumstances likely to be associated with change in renal function, such as dehydration or severe intercurrent illness. Where no previous creatinine values exist and the patient is otherwise stable, patients will not be excluded on the basis of unknown previous renal function.
- Known allergy to heparin/LMWHs or history of heparin induced thrombocytopenia
- Treatment with UFH, LMWH, danaparoid, oral direct thrombin inhibitors for >48 h
- Bleeding requiring hospitalization or blood transfusion within 6 months(exception is blood transfusion given in relation to surgical procedures within 6 months)
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 |
|---|---|---|
| TinzaparinAlso: Brand name: InnohepDose: 175 IU/kg subcutaneously once daily, up to 7 days. Dose reduction as per protocol if anti-Xa levels exceed pre-defined limits. | Drug | 1 |
Primary outcome
Anti-Xa level measured on any two of Days 3, 5 or 7 of treatment
Time frame: Up to 7 days of treatment
Results and safety
The study was stopped early (reason given: Funding ceased). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2016.
- Individual participant dataSharing planned: Undecided
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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.
Wendy Lim, MD principal investigator
St Joseph's Healthcare Hamilton / McMaster University
Mark A Crowther, MD principal investigator
St Joseph's Healthcare Hamilton / McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tinzaparin in people with Venous Thrombosis and Pulmonary Embolism, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
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 2 inclusion and 13 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: stopped early, as of the sponsor's last update on 19 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
Are results available for this study?
The study was stopped early (reason given: Funding ceased). Results are not available in the source record.
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?
Anti-Xa level measured on any two of Days 3, 5 or 7 of treatment (time frame: Up to 7 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Apr 2016.