Efficacy, safety and pharmaco-economic assessment of secondary long term prophylaxis with highly purified, standardized, doubly virus inactivated FVIII/VWF concentrates in patients with severe, inherited VWD and frequent bleedings - PRO.WILL

• Register: EUCTR
• Last refreshed on: 29 August 2016
• Main ID: EUCTR2006-001383-23-IT
• Date of registration: 28/11/2006
• Prospective Registration: No
• Primary sponsor: FONDAZIONE CENTRO EMOFILIA E TROMBOSI ANGELO BIANCHI BONOMI
• Public title: Efficacy, safety and pharmaco-economic assessment of secondary long term prophylaxis with highly purified, standardized, doubly virus inactivated FVIII/VWF concentrates in patients with severe, inherited VWD and frequent bleedings - PRO.WILL
• Scientific title: Efficacy, safety and pharmaco-economic assessment of secondary long term prophylaxis with highly purified, standardized, doubly virus inactivated FVIII/VWF concentrates in patients with severe, inherited VWD and frequent bleedings - PRO.WILL
• Date of first enrolment: 30/06/2006
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001383-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Profilassi vs terapia al bisogno
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
- Documented unresponsiveness to DDAVP. All the patients, excluding type 3 and type 2B, should have been exposed to a documented infusion trial with DDAVP. Responsiveness to DDAVP is defined as an increase in plasma FVIII C and VWF RCo levels of at least three fold over baseline and in absolute reaching at least 30 IU/dl for both values and a BT of 12 minutes or less after 2 hours from administration of 0,3 mcg/kg of DDAVP OR contraindication to DDAVP namely type 2B VWD patients or other patients who display significant side effects to DDAVP - Frequent, spontaneous bleedings i.e. at least 5 episodes in whatever anatomical site in the last 12 months, severe enough to require treatment with FVIII/VWF concentrates Note that prolonged or excess bleeding during menses is not considered among inclusion criteria in this study OR Recurrent spontaneous bleedings, severe enough to require treatment with FVIII/VWF concentrates of the following types 61607; Epistaxes at least 5 episodes in the last 12 months 61607; Haemarthroses at least 3 episodes at the same joint in the last 12 months 61607; Gastrointestinal bleeding at least 2 episodes in the last 12 months, with a drop 61619; 2 g/dl of haemoglobin in 24-48 hours due to unexplained reason or in association with underlying gastrointestinal angiodysplasia - Willingness to participate in the study, expressed by signed, written informed consent
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- a life expectancy 1 year - presence of allo-antibodies to VWF or FVIII - acquired Von Willebrand syndrome AVWS - co-morbidity with other haemorrhagic diathesis, excluded those linked to VWD as the complication of treatment for instance thrombocytopenia in Type 2B VWD - advanced liver cirrhosis with 61607; cirrhosis related coagulation abnormalities thrombocytopenia, defined as platelet count 50.000/mm3, INR 1,7, prolonged prothrombin time 4 seconds versus normal 61607; portal hypertension with history of variceal bleeding - pregnancy and lactation - any known need for invasive procedures or elective surgery scheduled in the following 3 months recruitment in these cases should be postponed - proven co-morbidity for other causes of gastrointestinal bleeding not related to the studied disease as drug induced haemorrhagic gastropathy, upper GI tract ulcers or cancer, or operable conditions, e.g. haemorrhoids with the exception of concomitant angiodysplasia which meets the inclusion criteria - gastrointestinal bleeding due to trauma, invasive diagnostic or surgical procedures - concomitant autoimmune anaemia and/or autoimmune thrombocytopenia


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

patients with severe inherited VWD unresponsive to DDAVP and with frequent bleedings
MedDRA version: 8.1 Level: PT Classification code 10047715 Term: Von Willebrand's disease

Intervention(s)

Trade Name: ALPHANATE*INF 1F 1500UI+F 10ML
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: FANHDI*INF FL 250UI+SIR SOLV+S

Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: FANHDI*INF FL 500UI+SIR SOLV+S

Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: ALPHANATE*INF 1F 250UI+F 5ML
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: ALPHANATE*INF 1F 500UI+F 5ML

Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: ALPHANATE*INF 1F 1000UI+F 10ML

Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: FANHDI*INF FL1000UI+SIR SOLV+S

Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: ALPHANATE*INF 1F 250UI+F 5ML
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 60-

Trade Name: FANHDI 250UI*1F 250UI+F 10ML
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Coagulation factor VIII
Concentration unit: IU international

Primary Outcome(s)

Primary end point(s): Primary end point is the prevention of spontaneous bleeding onset, expressed as proportion of patients who do not present any spontaneous bleeding episode during the study period. A bleeding is defined spontaneous when occurring in absence of concomitant trauma, local injury, invasive diagnostic or surgical procedures. Definitions are given for the most common bleeding events expected during the study - Gastrointestinal bleeding overt melena or presence of blood in stools, with haemoglobin loss 2 g/dl in 24 -48 hours, requiring treatment with FVIII/VWF concentrates or causing blood transfusion. Unrelated causes of bleeding should be ruled out as ulcers or tumors , with exception of angiodysplasia which meets an inclusion criterion - Haemarthroses pain, swelling, impaired motion in the joint - Haematoma pain, local swelling, impaired function if in muscles diagnosed by physical examination and/or by computed tomography scan and requiring treatment with FVIII/VWF concentrates or blood transfusion. - Epistaxis monolateral/bilateral blood loss from nostril, requiring FVIII/VWF concentrates infusion or blood transfusion Excess blood loss during menses is not considered as a primary end point as far as efficacy analysis is concerned. Each bleeding event must be evaluated by the appointed Investigator and accurately described in the Case Report Forms. Indeed instrumental or laboratory analyses e.g. stools analysis , or any Medical Consultancy when carried out should be attached to the clinical record and referred in the study Case Report Form.

Main Objective: To evaluate if long term, secondary prophylaxis with highly purified FVIII/VWF concentrates, with respect to on demand treatment with the same pharmacological agent, prevents spontaneous bleedings onset in patients with severe inherited VWD unresponsive to DDAVP and with frequent bleedings

Secondary Objective: Secondary objectives of the study will be to evaluate the effect of prophylaxis versus on demand therapy in the following - safety, with particular reference to the likelihood of thrombotic complications occurrence - patient compliance - possible impact on the global costs of care and on patients quality of life, describing and evaluating 61607; incremental cost per unit of effect 61607; the Health Related Quality of Life HRQoL of adult and paediatric patients and their caregivers

Secondary ID(s)

PROWILL