- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03167320
Low Von Willebrand in Ireland Cohort Study (LOVIC)
Study Overview
Status
Conditions
Detailed Description
All patients with bleeding disorders in Ireland are registered on a national bleeding disorder database and attend the National Coagulation Centre in St. James's Hospital, Dublin, Ireland or the paediatric centre, Our Lady's Children's Hospital Crumlin for annual review. At review eligible patients will be invited to participate in the Low Von Willebrand in Ireland Cohort (LOVIC) study.
Following consent, an extensive bleeding assessment tool will be administered by a coagulation haematologist to all participants from which the International Society of Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH BAT) and the Condensed Molecular and Clinical Markers for the Diagnosis and Management of Type 1 Von Willebrands Disease (MCMDM-1 VWD) scores can be derived. In addition, blood will be drawn for von Willebrand factor (VWF) measurements, VWF propeptide, platelet VWF. Citrated plasma and DNA will be stored for each patient. The relationship between laboratory parameters, (including von Willebrand factor, platelet VWF, FVIII and concomitant coagulation disorders) and the clinical phenotype in patients with low VWF will be studied. We will assess the effect of the laboratory parameters on the severity of bleeding tendency. In the future mutation analysis of the VWF gene will be performed in all participants in the LOVIC study.
Historical patient records and laboratory results will be reviewed and DDAVP (1-desamino-8-D-arginine vasopressin) fall off studies documented where available. If no previous DDAVP fall off study has been performed patients will be invited to attend.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Dublin, Ireland, D8
- Recruiting
- St. James's Hospital
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Contact:
- Michelle Lavin, FRCPath
- Phone Number: +35314162141
- Email: nchcd@stjames.ie
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Sub-Investigator:
- Niamh M O'Connell, FRCPath,PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) >30 IU/dL <50 IU/dL.
Exclusion Criteria:
- Pregnant patients
- Hospitalised patients/acutely unwell patients
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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LOVIC
Irish patients with low Von Willebrand levels will be have both venous blood sampling and a bleeding score administered at study entry.
A DDAVP (1-desamino-8-D-arginine vasopressin) fall off study was organised for those patients in the cohort with no previous fall offs available and no contraindications to DDAVP.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Irish patients with Low Von Willebrand Factor with abnormal bleeding scores
Time Frame: at enrolment
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The ISTH-BAT and Condensed MCMDM-1 VWD score of all participants will be determined at enrollment using a physician directed questionnaire using only symptoms prior to their diagnosis with Low VWF.
This will help elucidate the bleeding phenotype, if any, associated with Low VWF.
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at enrolment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The number of patients with Low VWF with abnormal plasma VWF clearance
Time Frame: 2 years
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For each individual enrolled the Von Willebrand factor propeptide (VWF:pp, U/dL), Von Willebrand factor antigen (VWF:Ag IU/dL) and Factor VIII:C (FVIII:C IU/dL) levels at enrolment will be determined.
From this data the plasma VWF clearance will be ascertained using the plasma VWF:pp/VWF:Ag ratio.
In addition, the FVIII:C/VWF:Ag ratio will be calculated to determine the contribution of altered VWF synthesis to Low VWF.
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2 years
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The rate of response to DDAVP in Irish patients with low Von Willebrand factor levels
Time Frame: 3 years
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For each individual with no contraindication a DDAVP trial will be performed with plasma VWF levels taken pre and at 1 and 4 hours post DDAVP.
The rate of plasma VWF level fall off for each trial will be determined and the area under the curve (AUC) calculated.
Complete response will be defined as a three fold increase from baseline.
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3 years
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The number of patients with Low VWF with reduced plasma VWF synthesis
Time Frame: 3 years
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For each individual enrolled the Von Willebrand factor antigen (VWF:Ag IU/dL) and Factor VIII:C (FVIII:C IU/dL) levels at enrolment will be determined.
From this data the plasma FVIII:C/VWF:Ag ratio will be calculated to determine the contribution of altered VWF synthesis to Low VWF.
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3 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: James S O'Donnell, MD,PhD, St. James's Hospital, Dublin Ireland
Publications and helpful links
General Publications
- Doherty D, Lavin M, Byrne MB, Nolan M, O'Sullivan JM, Ryan K, O'Connell NM, Haberichter SL, Christopherson P, Di Paola J, James PD, O'Donnell JS. Enhanced VWF clearance in Low VWF pathogenesis - limitations of VWFpp/VWF:Ag ratio and clinical significance. Blood Adv. 2022 May 6:bloodadvances.2022007340. doi: 10.1182/bloodadvances.2022007340. Online ahead of print.
- Aguila S, Lavin M, Dalton N, Patmore S, Chion A, Trahan GD, Jones KL, Keenan C, Brophy TM, O'Connell NM, Ryan K, Byrne M, Nolan M, Patel A, Preston RJS, James P, Di Paola J, O'Sullivan JM, O'Donnell JS. Increased galactose expression and enhanced clearance in patients with low von Willebrand factor. Blood. 2019 Apr 4;133(14):1585-1596. doi: 10.1182/blood-2018-09-874636. Epub 2019 Feb 15.
- Lavin M, Aguila S, Dalton N, Nolan M, Byrne M, Ryan K, White B, O'Connell NM, O'Sullivan JM, Di Paola J, James PD, O'Donnell JS. Significant gynecological bleeding in women with low von Willebrand factor levels. Blood Adv. 2018 Jul 24;2(14):1784-1791. doi: 10.1182/bloodadvances.2018017418.
- Lavin M, Aguila S, Schneppenheim S, Dalton N, Jones KL, O'Sullivan JM, O'Connell NM, Ryan K, White B, Byrne M, Rafferty M, Doyle MM, Nolan M, Preston RJS, Budde U, James P, Di Paola J, O'Donnell JS. Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels. Blood. 2017 Nov 23;130(21):2344-2353. doi: 10.1182/blood-2017-05-786699. Epub 2017 Sep 15.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- LOVIC01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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