Surveillance of Safety and Efficacy of Wilate in Patients With Von Willebrand Disease

Von Willebrand Disease Clinical Trial

Official title:

Surveillance of Safety and Efficacy of Wilate in Patients With Von Willebrand Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01602419
• Other study ID #: Wil-20
• Status: Completed
• Start date: October 2012
• Est. completion date: April 2018

Study information

• Verified date: December 2020
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational study, hence there is no study hypothesis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of von Willebrand Disease who have been prescribed Wilate

Related Conditions & MeSH terms

• Von Willebrand Disease
• Von Willebrand Diseases

Intervention

Other:
• Patients using Wilate as standard of care
Patients with von Willebrand Disease using Wilate for a period of 2 years.

Locations

Country	Name	City	State
Argentina	Fundación de la Hemofilia de Salta	Salta
Canada	University of Alberta	Edmonton	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Queens University	Kingston	Ontario
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	St. John Regional Hospital	Saint John	New Brunswick
Canada	Eastern Regional Health Authority	St. John's	Newfoundland and Labrador
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Czechia	University Hospital Ostrava	Ostrava-Poruba
Germany	Werlhof-Institut	Hannover
Portugal	Centro Hospitalar Cova da Beira	Covilhã
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Fundacion Jiminez Diaz	Madrid
Sweden	Skåne University Hospital	Malmö
United Kingdom	Great Ormond Street Hospital for Children	London
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Utah	Salt Lake City	Utah
United States	Los Angeles Biomedical Research Institute	Torrance	California
Uruguay	Hospital Pereira Rossell	Montevideo
Uruguay	Sanatorio Americano	Montevideo

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Uruguay,  Argentina,  Canada,  Czechia,  Germany,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety: Number of Exposure Days to Wilate	Number of exposure days to Wilate was documented throughout the observation period; EDs = exposure days. IU = international unit. SD = standard deviation.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 575 days [±326]; median [range]: 731 days [2-1185]).
Other	Safety: Frequency of VWF Inhibitors at Baseline and Follow up	Optional testing for anti-VWF antibodies/VWF inhibitor was performed at the baseline and follow up visits. VWF inhibitor testing was only performed if anti-VWF antibody results were positive. VWF antibody testing was performed using an ELISA assay, and inhibitor testing using a Bethesda assay. Both assays were considered experimental, since no standardized laboratory assays were available. Results displayed here are for confirmatory inhibitor testing.	Optional antibody tests were performed at baseline and 3-4 days (preferable 7 days) after Wilate injection.
Other	Adverse Drug Reactions (ADRs)	Patients with a positive inhibitor test were assessed for ADRs related to anti VWF antibody or inhibitor development	Optional antibody tests were performed at baseline and 3-4 days (preferable 7 days) after Wilate injection
Other	Safety: Patients With Thrombogenicity Values >2 Times the Upper Limit of Normal (ULN)	Thrombogenicity testing was optional. Thrombogenicity markers (prothrombin fragments 1 + 2; D-dimer) were evaluated at baseline and during follow up. Samples with prothrombin F1+2 and/or D-dimer values at least 2 times above the upper limit of normal were recorded as high.	Optional thrombogenicity tests were performed at baseline and 1, 3 and 24 hours after each administration of Wilate.
Other	Wilate Dosage Per Infusion for the Treatment of Acute Bleeding Episodes (BEs; On-demand)	The number of infusions and dosage of Wilate administered for the on-demand treatment of acute BEs was documented throughout the study.; n= number of infusions	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 677 days [±264]; median [range]: 749 days [40-1052]).
Other	Wilate Dosage for the Treatment of Acute Bleeding Episodes (BEs; On-demand) Per Bleeding Episode (BE)	The dosage of Wilate administered for the on-demand treatment of acute BEs was documented throughout the study.; n = number of BEs	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 677 days [±264]; median [range]: 749 days [40-1052]).
Other	Wilate Doses for the Treatment of Menstrual Bleeding Episodes (BEs)	Dosage of Wilate administered for treatment of menstrual BE's was documented throughout the study.; n = number of BEs treated	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 553 days [±296]; median [range]: 713 days [125-840]).
Other	Exposure Days for Prophylactic Treatment With Wilate	The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).
Other	Number of Infusions of Prophylactic Treatment With Wilate Per Week	The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).; n = number of patients.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).
Other	Dosage for Prophylactic Treatment With Wilate Per Week	The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).; n = number of patients	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).
Other	Dosage for Prophylactic Treatment With Wilate Per Infusion	The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population).	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).
Other	Exposure Days for Prophylactic Wilate Treatment on a Continuous Basis	Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.; The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).
Other	Number of Infusions Per Week for Prophylactic Wilate Treatment on a Continuous Basis	Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.; The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).
Other	Dosage for Prophylactic Wilate Treatment on a Continuous Basis	Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.; The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.; n = number of patients.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).
Other	Dosage for Prophylactic Wilate Treatment Per Infusion on a Continuous Basis	Number and dosage of Wilate infusions administered as prophylactic treatment on a continuous basis were documented throughout the study.; The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment.; n = number of infusions.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).
Other	Dosage of Wilate Per Infusion for the Treatment of Breakthrough Bleeds	Number and dosage of Wilate infusions administered as treatment for breakthrough bleeds in patients receiving prophylactic treatment on a continuous or intermittent basis were documented throughout the study. n = number of infusions	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 561 days [±251]; median [range]: 773 days [144-1185]).
Other	Dosage of Wilate for the Treatment of Breakthrough Bleeds Per Breakthrough Bleed	Number and dosage of Wilate infusions administered as treatment for breakthrough bleeds in patients receiving prophylactic treatment on a continuous or intermittent basis were documented throughout the study.; n = For 1 bleed in the EFF-PC population, the dose is unknown.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 561 days [±251]; median [range]: 773 days [144-1185]).
Other	Wilate Dosage Per Infusion for the Prevention of Bleeding During and After Surgery	Number and dosage of Wilate infusions administered to prevent bleeding during and after surgery were documented throughout the study.; For 6 infusions, no dosage information is available; One minor surgical procedure was not treated with Wilate. For 2 of the 98 treated surgical procedures, no dosage information is available (i.e., 1 major orthopaedic surgery and 1 minor cardiovascular surgery)	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 568 days [±349]; median [range]: 732 days [2-1185]).
Other	Wilate Dosage Per Procedure for the Prevention of Bleeding During and After Surgery	Number and dosage of Wilate infusions administered to prevent bleeding during and after surgery were documented throughout the study.; For 6 infusions, no dosage information is available; One minor surgical procedure was not treated with Wilate. For 2 of the 98 treated surgical procedures, no dosage information is available (i.e., 1 major orthopedic surgery and 1 minor cardiovascular surgery)	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 568 days [±349]; median [range]: 732 days [2-1185]).
Other	Number of Patients With Breakthrough Bleeds During Prophylaxis	Breakthrough bleeds in patients receiving Wilate as prophylactic treatment on a continuous (EFF-PC population) or intermittent (EFF-PI population) basis were documented throughout the study.	Throughout the duration of each patient's participation in the study (study duration: mean [±SD]: 761 days [±251]; median [range]: 773 days [144-1185]).
Primary	Incidence of Adverse Drug Reactions (ADRs) (%)	Medical Dictionary for Regulatory Activities (MedDRA) primary system organ class preferred term. Incidence rate = number of patients reporting the event / number of patients * 100	Throughout the duration of each patient's participation in the study (mean [± standard deviation (SD)]: 575 days [±326]; median [range]: 731 days [2-1185])
Primary	Tolerability Assessment of Wilate Infusions by Reason for Administration	Tolerability was assessed using a 3-point verbal rating scale (excellent; satisfactory; unsatisfactory) according to overall feeling during and after Wilate therapy and occurrence of ADRs.; Tolerability was assessed for infusions given for on-demand and prophylactic treatment, but not for infusions administered for surgeries or for the purpose of thrombogenicity assessment. In some instances, however, investigators also recorded the tolerability of infusions given for surgical prophylaxis. For infusions administered for surgeries, only those with available tolerability assessments are presented. Wilate infusion may have been administered to a patient for more than one reason and may be included in more than one category (e.g., if a patient was under Wilate prophylaxis, they could also receive Wilate for the treatment of a bleeding episode [BE] or surgery or menstruation).	During and immediately after each infusion of Wilate during the study.
Secondary	Patient and Investigator Efficacy Analysis Assessment of the Treatment of Bleeding Episodes (BEs)	Document the efficacy of Wilate in the treatment of acute BEs, breakthrough BEs in patients receiving prophylactic treatment, and menstrual BEs.; Efficacy was rated on a 4-point scale (excellent; good; moderate; none) according to overall haemostasis.	During and immediately after treatment of each BE.
Secondary	Efficacy Analysis for the Prevention of Breakthrough Bleeds During Prophylaxis	Efficacy was rated on a 4-point scale (excellent; good; moderate; none) according to the number of breakthrough bleeds per month. The treatment regimen for prophylactic treatment was at the discretion of the investigator and differed for each patient, as did the duration of prophylactic treatment. The prophylaxis efficacy population (EFF-P) was subdivided into 2 groups, prophylaxis on a continuous basis (EFF-PC population) and prophylaxis on an intermittent basis (EFF-PI population). In total, 25 patients received Wilate for prophylaxis and of these, 17 patients received prophylaxis on a continuous basis, which was defined as: (1) patients having received continuous prophylaxis over a period of at least 3 months, with no treatment gaps longer than 14 days; or (2) patients having received continuous prophylaxis for at least 1 year with an average of 1 infusion/per week (these patients may have had gaps of more than 14 days).	At the end of the study for each patient (study duration: mean [±SD]: 805 days [±247]; median [range]: 797 days [144-1185]).
Secondary	Efficacy Analysis of Surgical Prophylaxis	Efficacy was rated on a 4-point scale (excellent; good; moderate; none) according to overall haemostasis during and after surgery.	During and immediately after each surgery.
Secondary	Overall Efficacy Assessment by Patient and Physician at the End of the Treatment Period	Patient and investigator assessment of the overall efficacy of Wilate performed at the end of the study for each patient. Efficacy was rated on a 4-point scale (excellent; good; moderate; none); criteria for assessment were not defined.	At the end of the study for each patient (study duration: mean [±SD]: 596 days [±336]; median [range]: 732 days [2-1185]).