An observational study in Neoplasms and Venous Thromboembolism, sponsored by Assistance Publique - Hôpitaux de Paris. Status unknown at 8 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-10-19.
Sponsored by Assistance Publique - Hôpitaux de Paris · Observational
Low molecular weight heparins (LMWH) are the reference molecule for the long term treatment of venous thromboembolism (VTE) in cancer patients but remains, however, associated with a high risk of recurrent thromboembolism. The high rate of recurrence may result from alterations in the pharmacokinetics of LMWH. The primary purpose of the study is to compare the pharmacokinetics of anti-Xa activity in patients with cancer and patients without cancer treated with curative dose of low molecular weight heparins (LMWH) for venous thromboembolism (VTE). The secondary purposes are 1/ to study the correlation between anti-Xa LMWH and concentration of plasma heparanase and 2/ to evaluate the predictive nature of the anti-Xa activity on the occurrence of thromboembolic recurrence in cancer patients treated with LMWH for VTE.
Purpose of the study:
The primary purpose of the study is to compare the pharmacokinetics of anti-Xa activity in patients with cancer and patients without cancer treated with curative dose of low molecular weight heparins (LMWH) for venous thromboembolism (VTE).
The secondary purposes are 1/ to study the correlation between anti-Xa LMWH and concentration of plasma heparanase and 2/ to evaluate the predictive nature of the anti-Xa activity on the occurrence of thromboembolic recurrence in cancer patients treated with LMWH for VTE.
Study design:
Multicentre cohort study of patients hospitalized with VTE:
Study hypothesis:
Venous thrombosis and pulmonary embolism are a common complication of cancer. They complicate up to 10% of cancers and are the cause of fatality, morbidity and significant impaired quality of life. The treatment of these diseases is difficult in this context. Low molecular weight heparins (LMWH) are the reference molecule for the long term treatment of venous thromboembolism (VTE) in cancer patients. Outside this context, their pharmacological properties allow to administer a fixed dose without measuring anti-Xa activity. In the presence of cancer, their use remains, however, associated with a high risk of recurrent thromboembolism up to 9% after 6 months of treatment.
This high rate of recurrence may result from alterations in the pharmacokinetics of LMWH in the presence of a cancer. The synthesis of heparanase by tumor cells might cause a decrease in anti-Xa activity of LMWH and reduce their effectiveness. If this hypothesis is verified, it could result in a change in the management of thrombosis in cancer patients and lead to a dose adjustment of LMWH through the measurement of anti-Xa activity, which may allow reduce the incidence of thromboembolic relapses during treatment.
Enrollment (Target or Actual Number of Subjects):
Pharmacokinetics study In a preliminary unpublished study of 37 cancer and non-cancer subjects with the highest concentration of anti-Xa activity was measured. Included 100 subjects (50 cancer patients and 50 non-cancer) would detect a maximum level difference of anti-Xa activity in plasma of 0.20 between cancer patients and cancer-with a power of 90% and a risk of the first kind 5%.
A difference of 0.20 seems relevant from these preliminary data (median 0.46 vs 0.65), and returns to show that a cancer patient has over 70% chance of having a maximum concentration of anti-Xa activity below that of a free cancer patient (nonparametric Wilcoxon test).
After over 2 years of inclusion, the event rate is lower than expected (7%). The number of subjects required was therefore reassessed. To reach the number of 20 events necessary to our analysis, a total of 320 cancer subjects must therefore be included.
Target Follow-Up, duration :
Study duration: 5 years and 6 months (inclusion: 5 years follow-up: 6 months). Duration of participation: 3 a 10 days for non-cancer patients, 6 months for cancer patient.
Performance of the study:
Pharmacokinetics study Inclusion (as soon as the diagnosis is confirmed VTE): 1 tube of blood taken before the start of treatment (at the time of another blood sample) for determination of heparanase. After the start of treatment: 3 tubes of blood drawn for determination of anti-Xa activity.
Assays will be centrally performed, blinded from the clinical data and from the group knowledge of the group patient.
Follow-up visits: Collection of clinical data (recurrent thromboembolism, hemorrhage, death, tumor progression, cancer treatment since last visit, interruption of treatment with LMWH, thrombocytopenia, anemia), and removal of 1 tube of blood (at the time of a another sample) for determination of anti-Xa activity.
Thromboembolic recurrences will be validated centrally by an independent committee.
Prospects:
Reduce the incidence of thromboembolic recurrence in cancer patients treated with LMWH for VTE by adapting the dose of LMWH with anti-Xa activity in this population if the hypothesis is verified.
9,610 studies on the registry are indexed under Neoplasms; 2,508 are open to participants now.
This study's enrollment of 370 is above the median of 202 across 1,742 observational studies indexed under Neoplasms.
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Hospitalized patients in tertiary care hospitals participating to the study and treated with curative dose of low molecular weight heparins (LMWH) for venous thromboembolism (VTE).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Case:
Control:
Exclusion Criteria:
Case:
Control:
Patients hospitalized for Venous Thromboembolism and having a cancer. Inclusion (as soon as the diagnosis of venous thromboembolism is confirmed). One tube of blood taken before the start of treatment (at the time of another blood sample) for determination of heparanase. After the start of treatment: three tubes of blood drawn for determination of anti-Xa activity. Assays will be centrally performed, blinded from the clinical data and from the group knowledge of the group patient.
Patients hospitalized for Venous Thromboembolism and not having a cancer. Inclusion (as soon as the diagnosis of venous thromboembolism is confirmed). One tube of blood taken before the start of treatment (at the time of another blood sample) for determination of heparanase. After the start of treatment: 3 tubes of blood drawn for determination of anti-Xa activity. Assays will be centrally performed, blinded from the clinical data and from the group knowledge of the group patient.
anti-Xa activity
The measurement of anti-Xa activity will be performed four times during the initial treatment for each patient (or during the first 5 to 10 days of treatment) and will establish pharmacokinetic modeling (population type approach, nonlinear model mixed-effect) of the low molecular weight heparin therapy in subjects with cancer or not. In order to obtain a curve of relevant anti-Xa activity.
Time frame: 10 days
hemorrhage
Major hemorrhage: * hemorrhage at the origin of death; * symptomatic hemorrhage in a major organ such as intracranial hemorrhage, intra spinal, intraocular, retro peritoneal, intra-articular, pericardial and muscle bleeding causing a compartment syndrome * symptomatic hemorrhage causing a fall in hemoglobin of at least 2 g / dL or leading to a transfusion of at least two blood units. Other hemorrhage will be considered as non-major.
Time frame: 6 months
all cause mortality
Cause and date of death. The death will be classified as follows: * related to cancer; * secondary to bleeding; * secondary to a confirmed pulmonary embolism; * other cause; * unexplained sudden death that can be attributed to pulmonary embolism.
Time frame: 6 months
thromboembolic recurrences
All thromboembolic events diagnosed during the follow-up period will be considered in the analysis, whether symptomatic or discovered incidentally on radiographic examination for another reason, evaluation of tumor progression in particular. The recurrence of venous thrombosis should be confirmed objectively by the presence of a non-compressible venous segment in an initially compressible area or by the appearance of a new gap in the CT venography. The recurrence of pulmonary embolism must be confirmed by the appearance of a gap in a normal artery on the initial scanner or the more proximal extension of thrombosis on the 2nd scanner or the appearance of a segmental perfusion defect without abnormality of ventilation in an initially normal part on the initial scintigraphy or the initial scan.
Time frame: 6 months
This study is status unknown, as verified in Oct 2017. You cannot join it, but the record below documents what was studied.
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