NCT05628558: GIDEMHA

Genetic Influence of Genetic Factors Influencing the Desmopressin's Efficacy in Mild/Moderate Hemophilia A

Status unknown Last updated 28 November 2022

What this trial tests

trial testing Desmopressin in Hemophilia A, Mild in 800 participants. Status unknown.

Timeline

1 July 2020

Primary endpoint
1 December 2022

30 April 2023

Quick facts

Lead sponsor	Groupe Maladies hémorragiques de Bretagne
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	800
Start date	1 July 2020
Primary completion	1 December 2022
Estimated completion	30 April 2023
Sites	1 location across France

Drugs / interventions tested

• Desmopressin (DESMOPRESSIN) — full drug profile →

Conditions studied

• Hemophilia A, Mild — all drugs for Hemophilia A, Mild →
• Desmopressin — all drugs for Desmopressin →
• Factor VIII — all drugs for Factor VIII →

Sponsor

Groupe Maladies hémorragiques de Bretagne

Who can join

Adults 2 to 80, male only, with Hemophilia A, Mild or Desmopressin. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Hemophilia A (HA) is an X-linked bleeding disorder caused by mutations in the F8 gene. Bleeding in patients with moderate/mild HA can be treated with either FVIII concentrates or desmopressin (DDAVP). This drug acts as a vasopressin type 2-receptor agonist that causes endothelial cells to rapidly secrete von Willebrand factor (VWF) and factor VIII (FVIII) into the bloodstream. One advantage of DDAVP is that it increases the level of endogenous FVIII, thus avoiding the need for potentially immunogenic exogenous FVIII. It is also cheaper than FVIII concentrates. Finally, it is more widely available in pharmacies in all hospitals with emergency rooms and surgical facilities. DDAVP usually increases the basal FVIII (FVIII activity) level by 3- to 4-fold. Thus, complete correction of the FVIII level (\>0.5 IU.mL-1) was achieved in different series as early as 1 hour after its administration in 50-60% of patients with mild HA. Since responses to DDAVP vary widely between individuals, it is recommended that each patient undergoes a therapeutic test before treatment. Several factors influence the FVIII response to DDAVP. The two most important are basal FVIII levels and the F8 gene defect. Rare studies related to the effect of genotype on DDAVP responses, but included relatively small patient groups (\<100), with few patients sharing a similar genotype. As such, it has been difficult from a statistical point of view to formally demonstrate the influence of the F8 genotype on the DDAVP response.

The objectives of the GIDEMHA study (Genetic Influence of Desmopressin Efficacy in Mild/moderate Hemophilia A) are: description of the post-DDAVP FVIII pharmacokinetics (PK) in a large retrospective cohort of patients with mild/moderate HA, research of patients-related factors influencing this FVIII PK, and building of predictive population- and Bayesian-based models.

The study comprises 2 independent cohorts:

* GIDEMHA-1 includes patients who had a DDAVP test from 2010 to 2020 in 4 centers. The influence of F8 variants on post-DDAVP FVIII PK is first analyzed then age, VWF level, blood group, weigh and DDAVP doses.
* GIDEMHA-2 includes patients who had a DDAVP test from 2020 to 2023 in the previous 4 centers (Angers, Caen, Nantes and Rennes) plus patients who had a DDAVP test from 2010 to 2023 in 2 other centers (Brest and Tours). This is a replicative cohort allowing to build predictive models based on the above described influencing factors.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.