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

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

Study Overview

• Status: Completed
• Conditions: Von Willebrand Disease
• Intervention / Treatment: Other: Patients using Wilate as standard of care

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Argentina
  • Salta, Argentina
    • Fundación de la Hemofilia de Salta
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Vancouver General Hospital
  • New Brunswick
    • Saint John, New Brunswick, Canada
      • St. John Regional Hospital
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada
      • Eastern Regional Health Authority
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University
    • Kingston, Ontario, Canada, K7L 3N6
      • Queens University
    • Ottawa, Ontario, Canada
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
• Czechia
  • Ostrava-Poruba, Czechia
    • University Hospital Ostrava
• Germany
  • Hannover, Germany
    • Werlhof-Institut
• Portugal
  • Covilhã, Portugal
    • Centro Hospitalar Cova da Beira
• Spain
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcantara
  • Madrid, Spain, 28040
    • Hospital Fundacion Jiminez Diaz
• Sweden
  • Malmö, Sweden
    • Skåne University Hospital
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital for Children
• United States
  • California
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
• Uruguay
  • Montevideo, Uruguay
    • Hospital Pereira Rossell
  • Montevideo, Uruguay
    • Sanatorio Americano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

VWD patients of any gender, age, or VWD type

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients using Wilate as standard of care treatment; This patient population is being treated with Wilate as standard of care treatment	Other: Patients using Wilate as standard of care; Patients with von Willebrand Disease using Wilate for a period of 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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])
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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]).
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.
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]).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]).
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.
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
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.
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).
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]).

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 21, 2012

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: Wil-20