WONDERS: Wilate in Subjects With Von Willebrand Disease Who Undergo Surgery

• Sponsor: Octapharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01365546
• Collaborator: (none)
• Enrollment: 30
• Locations: 15
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Proportion of surgeries in which the primary endpoint (overall assessment) is classified as success.

Condition or Disease	Intervention/Treatment	Phase
Prevent Bleeding in Major Surgery	Biological: human VWF/FVIII concentrate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective, Open-Label, Multi-Center, Phase III CLinical Study to Investigate the Efficacy and Safety of Human Factor VWF/FVIII Concentrate (Wilate) in Subjects With Inherited Von Willebrand Disease Who Undergo Surgical Procedures
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: human VWF/FVIII concentrate	Biological: human VWF/FVIII concentrate; intravenous infusion. Dose based on subject's individual invivo-recovery

Outcome Measures

Primary Outcome Measures

1. Overall Hemostatic Efficacy (Success or Failure) of Wilate, Based on the Intra-operative Assessment of the Surgeon and the Post-operative Assessment by the Investigator Using a 4-point Ordinal Efficacy Scale. [30 Days]

   Efficacy of Wilate in surgical procedures was assessed intra-operatively by the surgeon and post-operatively by the investigator. The IDMC additionally conducted an independent adjudication of all hemostatic efficacy results ('secondary adjudication') and adjudicated the surgeons'/investigators' assessments of the intra- and post-operative assessments where there were discrepancies between the two assessments ('primary adjudication'). It was specified in the SAP that the study will be terminated early and success claimed if the two-sided 98.75% confidence interval (CI) for the overall success rate excludes and is greater than 0.60 (equivalent to 25 or more successes out of the 30 procedures).

Secondary Outcome Measures

1. Assessment of Intra-operative Hemostatic Efficacy [1 Day]

   The efficacy of Wilate during surgical procedures was assessed by a 4-point ordinal efficacy scale by the surgeon at the end of the surgical procedure and took the predicted versus actual blood loss and transfusion requirements into consideration. Outcome measure 1 takes the results of outcome measure 2 and 3 into consideration and is an overall assessment covering intra- and post-operative efficacy.

2. Post-operative Efficacy Assessment [up to 30 days]

   Post-operative efficacy was assessed by the investigator, covering the time period from the end of the procedure up to 24 hours following the last infusion of study medication. This assessment took the post-operative bleeding and oozing into consideration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with congenital VWD (von Willebrand Disease)

• Require therapy with a VWF (von Willebrand Factor) product to treat any major surgical procedure

Exclusion Criteria:

• Known coagulation disorder other than VWD

• Known history of, or suspected VWF or FVIII inhibitors

• Subjects with hepatic liver disease

• Known or suspected hypersensitivity or previous evidence of severe side effects to wilate or other VWF/FVIII concentrates

• Pregnant women in the first 20 weeks of gestation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana	United States	46260
2	UNC-CH Comprehensive Hemophilia Center	Chapel Hill	North Carolina	United States	27599
3	Blood Center of Wisconsin	Milwaukee	Wisconsin	United States	53201
4	SHAT Joan Pavel	Sofia		Bulgaria	1233
5	Christian Medical College	Vellore	Tamil Nadu	India	632004
6	Sahyadri Specialty Hospital	Pune		India	411004
7	Azienda Ospedaliero Universitaria Careggi	Florence		Italy	50133
8	Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
9	ULSS6 Vicenza Ematologia	Vicenza		Italy	36100
10	Sultan Quaboos University Hospital	Muscat		Oman	PC123
11	Instytut Hematologii i Transfuzjologii	Warsaw		Poland	0.-776
12	Fundeni Clinical Institute	Bucharest		Romania	022328
13	Louis Turcanu Childrens Emergency Hospital	Timisoara		Romania	300011
14	Hemophilia Comprehensive Care Center	Johannesburg		South Africa	2193
15	Ege University	Izmir		Turkey	35100

Sponsors and Collaborators

• Octapharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Octapharma
• ClinicalTrials.gov Identifier: NCT01365546
• Other Study ID Numbers: Wil-24
• First Posted: Jun 3, 2011
• Last Update Posted: Mar 9, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Von Willebrand Diseases

Study Results

Participant Flow

Arm/Group Title	Human VWF/FVIII Concentrate
Arm/Group Description	human VWF/FVIII concentrate: intravenous infusion. Dose based on subject's individual invivo-recovery
Period Title: Overall Study
STARTED	41
COMPLETED	30
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Human VWF/FVIII Concentrate
Arm/Group Description	human VWF/FVIII concentrate: intravenous infusion. Dose based on subject's individual invivo-recovery
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.7 (18.1)
Sex: Female, Male (Count of Participants)
Female	29 70.7%
Male	12 29.3%
Region of Enrollment (participants) [Number]
United States	7 17.1%
Poland	2 4.9%
Oman	2 4.9%
Romania	8 19.5%
Turkey	1 2.4%
Bulgaria	1 2.4%
South Africa	2 4.9%
Italy	5 12.2%
India	13 31.7%

Outcome Measures

1. Primary Outcome

Title	Overall Hemostatic Efficacy (Success or Failure) of Wilate, Based on the Intra-operative Assessment of the Surgeon and the Post-operative Assessment by the Investigator Using a 4-point Ordinal Efficacy Scale.
Description	Efficacy of Wilate in surgical procedures was assessed intra-operatively by the surgeon and post-operatively by the investigator. The IDMC additionally conducted an independent adjudication of all hemostatic efficacy results ('secondary adjudication') and adjudicated the surgeons'/investigators' assessments of the intra- and post-operative assessments where there were discrepancies between the two assessments ('primary adjudication'). It was specified in the SAP that the study will be terminated early and success claimed if the two-sided 98.75% confidence interval (CI) for the overall success rate excludes and is greater than 0.60 (equivalent to 25 or more successes out of the 30 procedures).
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Minor Surgery	Major Surgery	All Surgeries
Arm/Group Description	human VWF/FVIII concentrate: intravenous infusion. Dose based on subject's individual invivo-recovery
Measure Participants	9	21	30
Number (95% Confidence Interval) [participants]	9 22%	20 NaN	29 NaN

2. Secondary Outcome

Title	Assessment of Intra-operative Hemostatic Efficacy
Description	The efficacy of Wilate during surgical procedures was assessed by a 4-point ordinal efficacy scale by the surgeon at the end of the surgical procedure and took the predicted versus actual blood loss and transfusion requirements into consideration. Outcome measure 1 takes the results of outcome measure 2 and 3 into consideration and is an overall assessment covering intra- and post-operative efficacy.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-operative Assessment by IDMC
Arm/Group Description
Measure Participants	30
Number [participants]	27 65.9%

3. Secondary Outcome

Title	Post-operative Efficacy Assessment
Description	Post-operative efficacy was assessed by the investigator, covering the time period from the end of the procedure up to 24 hours following the last infusion of study medication. This assessment took the post-operative bleeding and oozing into consideration
Time Frame	up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Post-operative Assessment by IDMC
Arm/Group Description
Measure Participants	30
Number [participants]	27 65.9%

Adverse Events

Time Frame	Adverse events were collected for each patient over a period of 1 to approximately 6 month from signing the informed consent to study completion.
Arm/Group Title	Human VWF/FVIII Concentrate
Arm/Group Description	human VWF/FVIII concentrate: intravenous infusion. Dose based on subject's individual invivo-recovery
All Cause Mortality
	Human VWF/FVIII Concentrate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Human VWF/FVIII Concentrate
	Affected / at Risk (%)	# Events
Total	2/41 (4.9%)
Gastrointestinal disorders
Gastritis erosive	1/41 (2.4%)	1
Reproductive system and breast disorders
Vaginal Hemorrhage	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Human VWF/FVIII Concentrate
	Affected / at Risk (%)	# Events
Total	29/41 (70.7%)
Gastrointestinal disorders
Nausea	6/41 (14.6%)	7
Vomiting	6/41 (14.6%)	6
General disorders
Pain	4/41 (9.8%)	4
Pyrexia	4/41 (9.8%)	4
Injury, poisoning and procedural complications
Procedural Pain	8/41 (19.5%)	10
Investigations
Hemoglobin decreased	4/41 (9.8%)	6
Vascular disorders
Hypertension	4/41 (9.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Octapharma agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Octapharma supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial. Octapharma also reserves the right to review data prior to publishing and provide comments/changes within a certain time period.