Bleeding Incidence in VWD Patients Undergoing On-Demand Treatment

Von Willebrand Diseases Clinical Trial

Official title:

A Prospective, Multicenter, Non-Interventional Study Evaluating the Bleeding Incidence in Patients With Von Willebrand Disease Undergoing On-Demand Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04053699
• Other study ID #: WIL-29
• Status: Completed
• Start date: June 25, 2019
• Est. completion date: January 31, 2021

Study information

• Verified date: March 2023
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to prospectively obtain reliable data on the bleeding and treatment pattern of patients with VWD undergoing on-demand treatment with a VWF-containing product over a period of 6 months. The data obtained will be used as a basis for historical comparisons with the bleeding and treatment pattern obtained from a clinical study on the efficacy of prophylactic treatment with a VWF/FVIII concentrate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: January 31, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 66 Months and older

Eligibility

Inclusion Criteria:

Patients who meet all of the following criteria are eligible for the study:

• Male or female patients aged =5.5 years at the time of enrolment

• VWD type 1 (baseline von Willebrand factor activity [VWF:RCo], <30 IU/dL), 2A, 2B, 2M, or 3 according to medical history requiring substitution therapy with a VWF-containing product to control bleeding

• Currently receiving frequent on-demand treatment with a VWF-containing product

• In female patients of child-bearing potential using hormonal contraception, the medication class should remain unchanged for the duration of their study participation

• Voluntarily given, fully informed written and signed consent obtained before collection of any patient data

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for the study:

• Patients currently on prophylaxis for VWD (except for perioperative prophylaxis) as well as patients having received treatment once a month for menstrual bleeding, but not for any other bleeds

• Patients whose VWD treatment is planned to be switched from on-demand to prophylactic treatment in the next 6 months

• History, or current suspicion, of VWF or FVIII inhibitors

• Medical history of a thromboembolic event within 6 months before enrolment

• Severe liver or kidney diseases as described in the medical records

• Female patients with an existing or suspected pregnancy or who are breast-feeding at the time of enrolment

• Change in hormonal contraception within 6 months before enrolment

• Cervical or uterine conditions causing abnormal uterine bleeding (including infection or dysplasia)

• Other coagulation disorders or bleeding disorders due to anatomical reasons

• Participation in an interventional clinical study during the 6-month of study period

• Inability to complete the patient diary to reliably evaluate the type, frequency, and treatment of BEs during the 6-month study period

Related Conditions & MeSH terms

• Von Willebrand Diseases

Intervention

Drug:
• Von Willebrand Factor-Containing Product
Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country

Locations

Country	Name	City	State
Belarus	Republican Research Center for Radiation Medicine and Human Ecology	Gomel
Bulgaria	Specialized Hospital for Active Treatment of Haematological Diseases" EAD, Sofia	Sofia
Bulgaria	"UMHAT Sveta Marina" EAD.	Varna
Croatia	University Hospital Centre Zagreb	Zagreb
Hungary	Medical Centre Hungarian Defence Forces	Budapest
Hungary	Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ	Debrecen
Hungary	University Clinical Center, Department of Internal Medicine, Hematology	Pécs
Lebanon	American University of Beirut Medical Center	Beirut
Lebanon	Hotel Dieu de France Hospital	Beirut
Lebanon	Nini Hospital	Tripoli
Russian Federation	Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal	Kirov
Russian Federation	Morosovskaya Children Clinical Hospital, Moscow Health Department, Department of General Hematology with the Pathology of Hemostasis	Moscow
Ukraine	State Institution "National Children's Specialized Hospital "OKHMATDYT" of the Ministry of Health of Ukraine," Center of Hemostasis Pathology	Kyiv
Ukraine	Community Institution of Lviv Oblast Council "West-Ukrainian Specialized Children's Medical Center	Lviv
United States	Children's Healthcare of Atlanta	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Belarus,  Bulgaria,  Croatia,  Hungary,  Lebanon,  Russian Federation,  Ukraine, 

References & Publications (9)

Broderick CR, Herbert RD, Latimer J, Mathieu E, van Doorn N, Curtin JA. Feasibility of short message service to document bleeding episodes in children with haemophilia. Haemophilia. 2012 Nov;18(6):906-10. doi: 10.1111/j.1365-2516.2012.02869.x. Epub 2012 Jun 11. — View Citation

Castaman G, Goodeve A, Eikenboom J; European Group on von Willebrand Disease. Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica. 2013 May;98(5):667-74. doi: 10.3324/haematol.2012.077263. — View Citation

Hays RD, Spritzer KL, Schalet BD, Cella D. PROMIS(R)-29 v2.0 profile physical and mental health summary scores. Qual Life Res. 2018 Jul;27(7):1885-1891. doi: 10.1007/s11136-018-1842-3. Epub 2018 Mar 22. — View Citation

Maruish M. User's manual for the SF-36v2 Health Survey (3rd edition). Optum Incorporated; 2011.

Mondorf W, Siegmund B, Mahnel R, Richter H, Westfeld M, Galler A, Pollmann H. Haemoassist--a hand-held electronic patient diary for haemophilia home care. Haemophilia. 2009 Mar;15(2):464-72. doi: 10.1111/j.1365-2516.2008.01941.x. Epub 2009 Feb 16. — View Citation

Rodeghiero F, Castaman G, Tosetto A. How I treat von Willebrand disease. Blood. 2009 Aug 6;114(6):1158-65. doi: 10.1182/blood-2009-01-153296. Epub 2009 May 27. — View Citation

Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1994 Apr;71(4):520-5. — View Citation

Saris-Baglama, R,DeRosa, M, Raczek, A, Bjorner, J,Turner-Bowker, D, Ware, J. The SF-10™ Health Survey for Children: A User's Guide. QualityMetric Incorporated; 2007.

Sholapur NS, Barty R, Wang G, Almonte T, Heddle NM. A survey of patients with haemophilia to understand how they track product used at home. Haemophilia. 2013 Sep;19(5):e289-95. doi: 10.1111/hae.12170. Epub 2013 May 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Annualized Bleeding Rate (TABR)	The total annualized bleeding rate (TABR) will be calculated as the total number of spontaneous bleeds, traumatic BEs, and other BEs occurring in the time period between the start of data collection for each patient and the Study Completion Visit, divided by the duration (in years) between the start of data collection and the Study Completion Visit. Surgery periods, and BEs occurring within these surgery periods, will be excluded from the calculation of TABR.	Screening through study completion (6 months)
Secondary	Spontaneous Annualized Bleeding Rate (SABR)	Spontaneous annualized bleeding rate (SABR), calculated in analogy with TABR. This includes all bleeding episodes that occurred spontaneously.	Screening through study completion (6 months)
Secondary	Consumption of the VWF-containing Product	Data on the consumption of the VWF-containing product (VWF/FVIII IU/kg per month per patient) used for routine on-demand treatment	Screening through study completion (6 months)
Secondary	Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale	The efficacy assessment of bleeding episodes at the end of a BE was evaluated on a 4 point scale by the patient/legal guardian (together with the Investigator in case of on-site treatment) including the four items 'excellent,' 'good,' moderate,' and 'none.' The assessment was excellent when bleeding was completely stopped within 3 days in case of minor bleed, within 7 days in case of major bleed, and within 10 days in case of gastrointestinal bleed; Good when bleeding was completely stopped, but time and/or dose slightly exceeded expectations ; Moderate when bleeding could be stopped only by significantly exceeding time and/or dose expectations; and None when bleeding could be stopped only by using other VWF-containing products.	Screening through study completion (6 months)
Secondary	Number of Surgery With Successful/Unsuccessful Efficacy Assessment	Effectiveness of VWF-containing product in surgical prophylaxis based on the proportion of surgeries successfully treated. Overall treatment efficacy will be assessed at the end of the postoperative period by the treating physician using predefined criteria of 'Excellent', 'Good', 'Moderate/Poor' or 'None'.	From start of surgery until end of post-operative period (within 8 days after surgery)
Secondary	Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)	QoL assessment based on the results from the PROMIS-29 survey to monitor and evaluate the physical, mental, and social health in all patients, using a scale of a minimum score of 0 and a maximum score of 10, with higher scores representing a better outcome. The survey covers seven domains from the most relevant areas of self-reported health (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance and ability to participate in social roles and activities) for the majority of people with chronic illness. PROMIS scores have a mean of 50 and standard deviation (SD) of 10 in a referent population. Full details of cut off points for each domain can be found here: https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis/promis-score-cut-points	At screening visit
Secondary	Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)	QoL assessment based on the results from the SF-36v2 questionnaire to measure functional health and well-being in patients =16 years. SF-36v2 ranks 8 different domains using a scale standardized with a scoring algorithm to obtain a score ranging from 0 to 100.The eight health domains include physical functioning (PF), role physical (RP), bodily pain (BP), general health problems (GH), vitality (VT), social functioning (SF), role emotional (RE) and general mental health (MH). Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.	At screening visit
Secondary	Quality of Life (QoL) Assessed Using a 10-item Short Form Health Survey (SF-10)	QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients =5.5 and <16 years of age, in order to score physical and psychosocial health. SF-10 uses norm-based scoring where scales have a standardized mean value of 50 and standard deviation of 10.	At screening
Secondary	Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS)	Joint health status will be assessed using the Hemophilia Joint Health Score (HJHS), which has been specifically validated for the assessment of the clinical outcome in VWD. HJHS evaluates six index joints to produce a score between 0-124. Higher scores indicate worse joint health.	At screening
Secondary	Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score	Bleeding information from each menstrual period while in this study will be collected using the Pictorial Blood Loss Assessment Chart (PBAC). The PBAC will be provided to all female patients of child-bearing potential. The data documented in the PBAC and the investigator-calculated final score will be recorded in the eCRF. The PBAC records pad and tampon use (as either light [1 point], medium [5 points], or heavy [10 points] flow), clots (small [1 point] or large [5 points]), and flooding episodes (1 point each) which can be recorded as many times as necessary any day of the month. The PBAC is scored from 0 (no bleeding) onwards, with a score of >100 defining abnormal coagulation and heavy menstrual bleeding (corresponds to >80ml of blood loss per menstrual cycle).	Screening through study completion (6 months)
Secondary	Number of Participants With Adverse Drug Reactions (ADRs) Associated With Use of Wilate	Noxious and unintended reactions arising from the use of Wilate will be monitored throughout the study.	Screening through study completion (6 months)