E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Venous thromboembolism in patients with malignancies |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine the rate of major bleeing events in cancer patients receiving extended treatment with dalteparin ( more than 6 months and up to 12 months) for prevention of recurrent symptomatic venous thromboembolism (VTE). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be to determine (for all subjects and according to baseline renal function): 1) the rate of symptomatic recurrent VTEs (proximal DVT and or PE) during treatment; 2) time to symptomatic recurrent VTE; 3) the rate of minor bleeding events; 4) time to first major bleeding event; 5) time to first bleeding event (any bleeding event); and 6) the safety and tolerability of extended treatment with dalteparin.
Additional objectives will include an evaluation of the utility of measuring anti-Xa activity to manage dose adjustment in subjects who present with or develop severe renal impairment (creatinine clearance less than 30 ml/min) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age range: subjects must be ≥ 18 years of age. 2. Male and female subjects will be eligible for enrollment. 3. Females should be either of non-childbearing potential as a result of surgery, radiational therapy, menopause (have been in menopause for ≥1 year), or of childbearing potential and willing to adhere to an acceptable method of pregnancy prevention 4. Subjects must be newly diagnosed, symptomatic proximal deep-vein thrombosis of the lower extremity, pulmonary embolism, or both. 5. Subjects must have active malignancy defined as a diagnosis of cancer (excluding basal cell or squamous cell carcinoma of the skin) within six months before enrollment, having received any treatment for cancer within the previous six months, or having documented recurrent or metastatic cancer. 6. Prior to enrollment, subjects must not have received therapeutic doses of heparin or LMWH for >96 hours ( or > 8 doses within 96 hours) or oral antigoagulant therapy for > 48 hours (or > 2 doses within 48 hours). 7. ECOG performance status of 0, 1 or 2. 8. Subjects must have a life expectancy of > 6 months. 9. Subjects must have a platelet count of > 75,000 mm3. 10. The subject must not be on any oral anticoagulant therapy for concomitant diseases with the exception of acetylsalicylic acid (ASA). No other systemic anticoagulants are allowed during the study with the exception of allowance of institution-specific I.V. line patency protocols 11. Subjects must have no active or serious bleeding episodes within two weeks prior to study entry. 12. Subjects must be able to comply with scheduled follow-ups. 13. Subjects must give written informed consent |
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E.4 | Principal exclusion criteria |
1. Subjects who have a high risk of serious bleeding (e.g. recent neurosurgery within 30 days, history of intracranial hemorrhage, acute gastroduodenal ulcer, etc.). 2. Subjects who are on hemodialysis. 3. Subjects who have a prior placement of a greenfield filter or other device to prevent embolization of DVTs. 4. Subjects with a known contraindication to the use of heparin (e.g. heparin-induced thrombocytopenia). 5. Subjects with a known hypersensitivity to heparin, dalteparin, other LMWHs or pork products. 6. Subjects who are currently participating in a clinical trial involving anticoagulation therapy (with the exception of acetylsalicylic acid (ASA), in the 30 days prior to study entry, or who is actively using any investigational drugs/treatments 30 days prior to study entry involving anticoagulation therapy (with the exception of ASA< t.i.d.). 7. Subject is pregnant or breast feeding. 8. Subjects with uncontrolled hypertension characterized by a sustained systolic pressure > 170 mmHg and/or diastolic pressure > 100 mmHg. 9. Subjects with a serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the subject?s ability to complete the study. 10. Any condition that makes the subject unsuitable in the opinion of the investigator. 11. Subjects with leukemia or myeloproliferative syndrome.
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E.5 End points |
E.5.1 | Primary end point(s) |
The Central Adjudication Committee assessments for VTEs will be used as the primary assesment in the efficacy analysis. The investigator?s assessments will also be collected and used as secondary assessments in the analyses. The proportion of subjects with symptomatic, new or recurrent, lower limb DVT, PE, or CVT occurring while the subject is on treatment with dalteparin will be summarised together with the two-sided 95% confidence interval. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study duration for each patient is 52 weeks. The end of the trial is the last visit of the last patient with completion of end of study assesments. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |