The aim of this project is to investigate the association between clinical and genetic factors and DDAVP response in MHA patients and to determine their relative contributions to the DDAVP response.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are:
- Clinical factors that determine DDAVP response
- Genetic factors that determine DDAVP response
The main study endpoint is the response to DDAVP, which is defined as complete
(1h after DDVP FVIII: C >0.50 IE/ml), partial (1h after DDVP FVIII: C 0.30-0.50
IE/ml), or none (1h after DDVP FVIII: C < 0.30 IE/ml). Therapeutic response
will also be evaluated.
Secondary outcome
N.a.
Background summary
Mild Hemophilia A (MHA) usually presents as a mild to moderate bleeding
disorder that occurs in one in 10 000 men and is a hereditary disease. MHA is
caused by a deficiency of clotting factor VIII. More personalised, safer and
cheaper treatment strategies for MHA are needed. In most MHA patients, FVIII: C
levels increase to a hemostatic range after DDAVP administration, a synthetic
analogue of vasopressin. This decreases the need for FVIII concentrates, and
thereby reduces the associated risk of inhibitor development and cost of
treatment. However, a yet undetermined proportion of patients partially or
completely fail to respond to DDAVP. Single center studies have demonstrated an
association between DDAVP response and clinical and genetic determinants.
However, their relative contribution remains unknown.
Understanding the clinical and genetic determinants for the DDAVP response may
enable better prediction and optimal clinical use of DDAVP. Furthermore,
identifying genetic predictors of DDAVP response will help to understand
biological mechanisms associated with the release of vWF and rise in FVIII: C.
Study objective
The aim of this project is to investigate the association between clinical and
genetic factors and DDAVP response in MHA patients and to determine their
relative contributions to the DDAVP response.
Study design
The RISE is an international multicenter cohort study that analyses the
response of MHA patients to DDAVP. The cohort will include all MHA patients who
have received DDAVP from the participating Hemophilia Treatment Centers (HTCs)
between 1980 and 2013.
Study burden and risks
N.a.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Moderate/mild hemophilia: defined as a FVIII deficiency with a FVIII:C plasma concentration of 2-40 IU/DL.
Treated or tested with DDAVP (between 1980 and 2013), and documented FVIII and VWF plasma levels prior to DDAVP administration and at least for 1 time point after DDAVP administration.
Exclusion criteria
Severe hemophilia A patients (factor VIII <1 IU/DL ) will be excluded from the study population.
The patient has other bleeding disorders, especially von Willebrand Disease (documented vWF plasma levels are available)
Type 2N von Willebrand Disease, or highly likely that patient has this disease since there are female bleeding patients in the pedigree
First DDAVP test is not taken at current hemophilia treatment center
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42418.018.12 |