E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
von Willebrand disease (VWD) is an inherited bleeding disorder, characterised mainly by mucosal bleedings, which may be life-threatening, and joint bleeds in severe VWD cases. VWD is caused by a lack of von Willebrand factor (VWF) and coagulation factor VIII (FVIII). Treatment of VWD aims at normalizing the VWF activity in plasma, which can be achieved by stimulating the endogenous release of VWF with desmopressin (DDAVP, 1-desamino-8-D arginine vasopressin) or by infusion of a VWF concentrate. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To correlate the biological response (and kinetics of FVIII/VWF activities) with clinical efficacy of Desmopressin (DDAVP) in type 1 and 2 VWD patients. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the biological response in a large number (at least 150, world-wide) of well characterized VWD patients To correlate kinetic data of VWF and FVIII to different subtypes of VWD. To determine the rate of clinical efficacy of DDAVP in different bleeding episodes and during surgery in different subtypes of VWD To evaluate the efficacy of dirrerent modes of administration in clinical practice To register side effects To develop treatment guidelines
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Well-characterized VWD patients with all type 1 and 2 (including 2B if treatment with DDAVP is allowed in any centre), with the widest range of age (from young children to senior adults). Due to the increased number of blood sampling, kinetic studies will be performed in patients older than 12 only.
Diagnosis of type 1 and 2 VWD should be correctly performed by the participating centre following recommendations provided by the ISTH-SSC on VWF. If available, molecular diagnosis (mutations) should also be reported to confirm classification in a specific VWD type. In a few patients, to be considered undefined because of a difficult diagnosis, plasma samples should be kept and sent, upon request by the Centre, to a more experienced laboratory. All these difficult diagnosis will be confirmed by the Steering Committee by using clinical and laboratory data.
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E.4 | Principal exclusion criteria |
Patients should be excluded from the study in the following cases: a) Acquired von Willebrand Syndrome; b) Additional congenital and acquired defects of platelet function (ex, Acquired Storage Pool defect + VWD); c) use of anti-inflammatory drugs that may affect platelet function within the previous 10 days; d) previous history of seizures in the family; e) recent serious cardiovascular episodes (Acute myocardial infarction and stroke) in the VWD patient. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is the correlation between biological response (maximum levels and kinetics of VWF and FVIII) and clinical response.
Criteria for definition of clinical response. The clinical effects of DDAVP will be evaluated by using the following evaluation scale: Excellent: No excessive bleeding; Good: Excess bleeding without need for VWF concentrate treatment; Poor: Excess bleeding with need for VWF concentrate treatment. The loss of blood during surgery will be evaluated directly by the surgeon and indirectly by the actual reduction of haemoglobin.
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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 | Information not present in EudraCT |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open prospective observational study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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Included patients will be followed for two years after the initial test doses. Patients should be included before the end of 2005. Therefore, the trial will end in the end of 2007, when the last of the included patients have finalized the two-year follow-up period. Patients included into the pharmacokinetic study, may however be included until June 30, 2006 and may thereafter be followed for two years, until June 2008. |
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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 | |
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 |