Von Willebrand Factor, DeficiencyLOVICNCT03167320
Low Von Willebrand in Ireland Cohort Study
An observational study of Von Willebrand Factor, Deficiency, run by St. James's Hospital, Ireland at 1 site in Ireland.
Trial summary
The Low Von Willebrand in Ireland Cohort (LoVIC) study focuses on the bleeding phenotype and biological mechanisms underlying low Von Willebrand Factor (VWF) levels. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Von Willebrand Factor, Deficiency
- How many people
- 400 participants
- Where
- 1 siteIreland
- Study dates
- Oct 2014to Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals (adults/children >3 years) with low Von Willebrand Factor (VWF) levels; defined as two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) >30 IU/dL <50 IU/dL.
Who may be able to join
- Two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) >30 IU/dL <50 IU/dL.
Who cannot join
- Pregnant patients
- Hospitalised patients/acutely unwell patients
Trial locations and contacts
1 site in 1 country.
Ireland1 site, 1 recruiting
- Recruiting
St. James's Hospital
Dublin, D8
Michelle Lavin, FRCPath, +35314162141, nchcd@stjames.ie
Niamh M O'Connell, FRCPath,PhD
About this study
The Low Von Willebrand in Ireland Cohort (LoVIC) study focuses on the bleeding phenotype and biological mechanisms underlying low Von Willebrand Factor (VWF) levels.
Read the 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.
- Conditions
- Von Willebrand Factor, Deficiency
- Medical subject headings
- Von willebrand factor, deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Irish patients with Low Von Willebrand Factor with abnormal bleeding scores
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.
Measured: at enrolment
Secondary outcomes (3)
The number of patients with Low VWF with abnormal plasma VWF clearance
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.
Measured: 2 years
The rate of response to DDAVP in Irish patients with low Von Willebrand factor levels
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.
Measured: 3 years
The number of patients with Low VWF with reduced plasma VWF synthesis
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study startOct 2014
- Primary completionJul 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Von Willebrand Factor, DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. James's Hospital, Ireland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James O'Donnell, St. James's Hospital, Ireland
- Investigators
- James S O'Donnell, MD,PhD, Principal investigator, St. James's Hospital, Dublin Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03167320
- Sponsor's protocol ID
- LOVIC01
- Acronym
- LOVIC
- Status last verified
- Mar 2019
- First submitted
- 6 Apr 2016
- Last updated
- 28 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Doherty D, Michelle Lavin, Byrne M, Nolan M, O'Sullivan JM, Ryan K, O'Connell NM, Haberichter SL, Christopherson PA, Di Paola J, James PD, O'Donnell JS. Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance. Blood Adv. 2023 Feb 14;7(3):302-308. doi: 10.1182/bloodadvances.2022007340.
PubMed 35523118Aguila 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.
PubMed 30770394Lavin 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.
PubMed 30042144Lavin 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.
PubMed 28916584
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Von Willebrand in Ireland Cohort Study
- ClinicalTrials.gov ID
- NCT03167320
- Acronym / sponsor ID
- LOVIC / LOVIC01
- Conditions
- Von Willebrand Factor, Deficiency
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- St. James's Hospital, IrelandUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 25 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Low Von Willebrand in Ireland Cohort (LoVIC) study focuses on the bleeding phenotype and biological mechanisms underlying low Von Willebrand Factor (VWF) levels.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals (adults/children >3 years) with low Von Willebrand Factor (VWF) levels; defined as two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) >30 IU/dL <50 IU/dL.
Key inclusion criteria (1 listed)
- Two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) >30 IU/dL <50 IU/dL.
Key exclusion criteria (2 listed)
- Pregnant patients
- Hospitalised patients/acutely unwell patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of Irish patients with Low Von Willebrand Factor with abnormal bleeding scores
Time frame: at enrolment
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.
3 secondary outcomes
The number of patients with Low VWF with abnormal plasma VWF clearance
Time frame: 2 years
The rate of response to DDAVP in Irish patients with low Von Willebrand factor levels
Time frame: 3 years
The number of patients with Low VWF with reduced plasma VWF synthesis
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2019.
- Derived from this study: PubMed 35523118Doherty D, Michelle Lavin, Byrne M, Nolan M, O'Sullivan JM, Ryan K, O'Connell NM, Haberichter SL, Christopherson PA, Di Paola J, James PD, O'Donnell JS. Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance. Blood Adv. 2023 Feb 14;7(3):302-308. doi: 10.1182/bloodadvances.2022007340.
- Derived from this study: PubMed 30770394Aguila 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.
- Derived from this study: PubMed 30042144Lavin 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.
- Derived from this study: PubMed 28916584Lavin 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.
- Individual participant dataSharing planned: Undecided
Related trials for Von Willebrand Factor, Deficiency
RecruitingObservational study
External Multicenter Validation of the APTTO Model for Prolonged APTT Using Clot Waveform Analysis
Coagulation Disorder, Blood, Prolonged APTT
RecruitingObservational study
ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
Hematologic Disorder, Bleeding Disorder
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James S O'Donnell, MD,PhD principal investigator
St. James's Hospital, Dublin Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Von Willebrand Factor, Deficiency, run by St. James's Hospital, Ireland at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michelle Lavin, FRCPath (+35314162141, nchcd@stjames.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Irish patients with Low Von Willebrand Factor with abnormal bleeding scores (time frame: at enrolment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03167320, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2019.