To show a reduction in FVIII-concentrate consumption with perioperative desmopressin and FVIII concentrate combination treatment compared to FVIII concentrate monotherapy, without decreasing the effectivity of treatment.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The average deviation of the measured FVIII level before the minor intervention
to the predicted peak FVIII values in IU/mL and the FVIII-concentrate
consumptionfor the first 24 hours around the minor intervention.
Secondary outcome
- Treatment costs in both arms
- Number and nature of bleeding during the first 14 days after the minor
intervention (appendix VI)
- Other adverse events during the first 14 days after the minor intervention
- The proportion of patients with FVIII plasma levels within set target levels
after the minor intervention
- Experienced quality of care in participating patients
- Discrepancies between one-stage and chromogenic FVIII-measurements before and
after desmopressin administration
- Inhibitor measurements 4-6 weeks after the minor intervention
Background summary
Hemophilia A (HA) is a rare bleeding disorder, caused by factor VIII
deficiency. In non-severe HA patients, minor interventions, such as dental
surgery and endoscopies, are an important treatment indication. Two treatment
options are currently available: FVIII concentrate and desmopressin.
Unfortunately, perioperative treatment is not optimal, as bleeding rates after
dental surgery, the most important type of minor interventions, of 12% and 25%
were found in two recent studies. Moreover, a previous evaluation of FVIII
concentrate treatment from our centre shows a high rate of dosing above FVIII
target levels (79%) and a low rate of dosing below FVIII target levels of 8%.
Both may lead to complications. Moreover, FVIII concentrate is expensive.
Pharmacokinetic (PK) guided dosing, a patient tailored dosing method, can
improve dosing accuracy.
Desmopressin, the second treatment option, releases endogenous FVIII and von
Willebrand factor, improving haemostasis. Desmopressin is not ideal due to
several barriers. Amongst others, most patients do not reach sufficient FVIII
levels to undergo minor interventions. An increase in the use of desmopressin
instead of FVIII concentrate would be highly beneficial, as desmopressin is
cheaper and more widely available. Desmopressin and FVIII concentrate
combination treatment may be an innovative treatment option.
Study objective
To show a reduction in FVIII-concentrate consumption with perioperative
desmopressin and FVIII concentrate combination treatment compared to FVIII
concentrate monotherapy, without decreasing the effectivity of treatment.
Study design
Randomized controlled trial
Intervention
The first group receives standard treatment consisting of FVIII concentrate
monotherapy. The intervention group receives desmopressin and FVIII concentrate
combination treatment.
Study burden and risks
This study aims to assess desmopressin and FVIII concentrate combination
treatment in non-severe hemophilia A patients undergoing a minor intervention.
During combination treatment, we will monitor FVIII plasma levels to guarantee
safety.
Preoperative desmopressin-testing in each individual will be performed
according to the desmopressin-testing protocol in each participating centre.
During this procedure, a standard dose of desmopressin is infused and FVIII
response is evaluated by measuring FVIII levels before and after desmopressin
administration. Patients who have undergone a desmopressin-test in the past
with admissible test results, will not have to undergo an additional
desmopressin-test.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible for this study, a subject must meet all of the
following criteria:, - Non-severe hemophilia A patients (FVIII 0.01-0.40
IU/mL), - In need of a minor surgical intervention, - Age minimally 12 and
maximally 70 years at study inclusion date, - Need for perioperative FVIII
concentrates for a maximum of 48 hours, - Having admissible results of a
desmopressin test (see paragraph 3.1), - Absolute increase in FVIII 1 hour
after desmopressin administration * 0.2 IU/mL after a previous (test) dose, -
Male gender, - (Parental) informed consent
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:, - Patients with other congenital or acquired
hemostatic abnormalities, - Clinically relevant FVIII inhibiting antibodies
(>0.5 BU) preoperatively, unless successfully treated with immunotolerance
therapy, - Needed treatment duration with FVIII concentrates longer than 48
hours, - Contraindications for desmopressin, e.g. cardiovascular disease , -
Use of co-medication that has an interaction with desmopressin , - Intolerance
to previous desmopressin administrations
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | 6036 |
| EudraCT | EUCTR2016-001875-57-NL |
| CCMO | NL57682.078.16 |
| OMON | NL-OMON26618 |