Carrier of Hemophilia AGIDEHACNCT06020456
Genetic Factors of the Desmopressin Response in Carriers of Hemophilia A
An observational study of Carrier of Hemophilia A and Desmopressin, run by Groupe Maladies hémorragiques de Bretagne at 12 sites in France.
Trial summary
Hemophilia A (HA) is a rare X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII) affecting 1/5,000 males1. Carriers of HA are females carrying the pathogenic variant responsible for the familial HA at a heterozygous status. Read more about this study
- Who is it for?
- Ages 2 to 80 years, women only
- Conditions the study is for
- Carrier of Hemophilia A, Desmopressin, Factor VIII Deficiency
- What is being tested?
- Desmopressin
- Type of treatment
- Injection or infusion
- How many people
- 361 participants
- Where
- 12 sitesFrance
- Study dates
- 1 Jan 2022to 1 Apr 2023
- 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 2 to 80 years
- Women only
- Child, Adult, Older adult
Study population: The study includes carriers of hemophilia A of any age who had a desmopressin therapeutic test during the last 10 years, associated with FVIII levels measurements before/after desmopressin. All procedures of the desmopressin therapeutic tests comprised an intravenous infusion of 0.3-0.4 μg.kg-1 diluted in 50 mL of saline solution over 30 minutes, associated with FVIII levels measured before and at least 30 or 60 minutes after the desmopressin infusion. Subsequent measurements performed at T2h, T4h and T6h after the infusion are also recorded during the test. All the data collected in this study were issued from the medical files including: pre/post desmopressin FVIII and VWF levels, F8 mutation, severity of the familial hemophilia A blood group, desmopressin doses, age, and weight.
Who may be able to join
- Females at any ages with a formal diagnosis of HA carriers based on the F8 genetics,
- Patients having received DDAVP during the last 10 years that was associated with dosages of FVIII before and just after DDAVP,
- Factor VIII levels measurements realized at least 2 times during the therapeutic test, just before the DDAVP infusion and 30 or 60 minutes after.
Who cannot join
- Patients with an anti-factor VIII inhibitor,
- Refusal to participate in the study,
- Unable to understand the study's French letter of non-opposition and information
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
France12 sites
University hospital of Bordeaux
Bordeaux, 33604
University hospital of Brest
Brest, 29609
Hospices civils de Lyon
Bron, 69677
University hospital of Dijon
Dijon, 21079
University hospital of Bicêtre
Le Kremlin-Bicêtre, 94270
University hospital of Lille
Lille, 59037
Assistance publique hôpitaux de Marseille
Marseille, 13385
University hospital of Montpellier
Montpellier, 34295
University hospital of Nancy
Nancy, 54500
University hospital of Nantes
Nantes, 44093
University hospital of Rennes
Rennes, 35033
University hospital of Saint Etienne
Saint-Etienne, 42055
About this study
Official title: Study of Genetic Factors Influencing the Factor VIII Response to Desmopressin in Carriers of Hemophilia A: the GIDEHAC Study
Hemophilia A (HA) is a rare X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII) affecting 1/5,000 males1. Carriers of HA are females carrying the pathogenic variant responsible for the familial HA at a heterozygous status. About 30% of HA carriers have low FVIII levels and can therefore have abnormal bleeding symptoms2,3. Such as males with moderate/mild HA, bleeding can be treated or prevented with either FVIII concentrates or desmopressin4,5. This drug acts as a vasopressin type 2-receptor (V2R) agonist that causes endothelial cells to rapidly secrete von Willebrand factor (VWF) and FVIII from Weibel-Palade bodies into the bloodstream6,7. However, the mechanism of action of post-DDAVP FVIII increase remains poorly understood in hemophilia A. 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.
The FVIII response profile to DDAVP in carriers appears quite similar to that seen in men with mild/moderate HA8-11. A post-DDAVP increase in the FVIII level of 2-4 fold the basal level is usually observed. This FVIII response presents an important inter-individual variation making it necessary to carry out a therapeutic test before its use for the anti-hemorrhagic treatment. The basal FVIII level logically conditions the intensity of the post-DDAVP FVIII peak. However, other factors influencing the post-DDAVP FVIII response are very likely. Unfortunately, few series describing the FVIII response to DDAVP in HA carriers have been reported to date and they included too small numbers of patients to precisely analyze the factors of variation in the post-DDAVP FVIII pharmacokinetics (PK). Candy et al did not find any difference depending on the severity of the pathogenic variants for HA or on the age11. However, this study was carried out in a cohort including only 17 patients, therefore too small for a reliable statistical analysis.
The GIDEHAC study (Genetic Influence of Desmopressin Efficacy in Hemophilia A Carriers) is a French study with the following objectives: the description of the post-DDAVP FVIII PK in a large retrospective cohort of HA carriers, the research of patients-related factors influencing this FVIII PK, and the building of predictive population- and Bayesian-based models.
Read the detailed description
The GIDEHAC study is a French observational, retrospective, and multicentric study performed in carriers of hemophilia A of any age who have received the intravenous desmopressin in their French Hemophilia Treatment Centers (HTC).
Objectives of the GIDEHAC study:
- Description of the post-desmopressin (DDAVP) FVIII pharmacokinetics (PK) in a large retrospective cohort of patients with mild/moderate HA,
- Research of patients-related factors influencing this FVIII PK,
- Building of predictive population- and Bayesian-based models
Inclusion criteria:
- Females at any ages with a confirmed diagnosis of HA carriers based on the F8 gene analysis,
- Patients having received DDAVP during the last 10 years that was associated with dosages of FVIII before and just after DDAVP,
- Factor VIII levels measurements realized at least 2 times during the therapeutic test, just before the DDAVP infusion and 30 or 60 minutes after.
Exclusion criteria:
- Patients with an anti-factor VIII inhibitor,
- Refusal to participate in the study,
- Unable to understand the study's French letter of non-opposition and information.
Description of the DDAVP therapeutic tests:
The procedure of the DDAVP therapeutic test was identical for all investigator centers as recommended by international and French guidelines. DDAVP was so always administered intravenously at a dose of 0.3-0.4 μg.kg-1 diluted in 50 mL of saline solution over 30 minutes. The required hemostatic parameters are FVIII levels before and at least 30 or 60 minutes after the DDAVP infusion. Subsequent FVIII measurements performed at T2h, T4h and T6h after the infusion are also recorded during the test.
Collected data:
All data collected in this study were issued from the medical files at the moment of the DDAVP therapeutic test. They include:
- FVIII activity levels measured with a one-stage clotting assay from plasmas collected in 0.109 M sodium citrate (fresh or stored at -80°C). These FVIII levels were measured just before and after the DDAVP infusion (until 24 hours if available),
- The pathogenic variant of the F8 gene responsible for the familial HA,
- Blood group,
- DDAVP doses,
- Von Willebrand factor levels during the DDAVP test,
- Age,
- Weight,
- FVIII levels measured during pregnancies,
- The degree of familial link if relatives are included in this study.
Pharmacokinetic analyses The following FVIII and VWF pharmacokinetic parameters are calculated using a compartmental approach with non-linear models at mixed effect (MONOLIX software, v2021, Lixsoft): basal FVIII and post-DDAVP FVIII peak (highest level measured after DDAVP administration), FVIII recovery (recFVIII = peak FVIII / basal FVIII), FVIII half-life (FVIII T1/2), FVIII clearance, FVIII area under the curve (FVIII AUC), and duration with FVIII ≥0.5 and 0.8 IU.dL-1.
Scores measuring the FVIII response to DDAVP
For qualitative assessment of the biological response to DDAVP, criteria previously reported by Stoof et al were used:
- The absolute response was either "complete" (peak FVIII ≥0.5 IU.mL-1), "partial" (FVIII ≥0.3 - <0.5 IU.mL-1) or "null" (FVIII <0.3 IU.mL-1).
- The relative response was defined as "complete" (recFVIII >3), "partial" (recFVIII ≥2 - <3) or "null" (recFVIII <2).
- Being tested
- Desmopressin
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DesmopressinDrug
For the 2 groups, all patients have received an intravenous DDAVP 0,3-0,4 µg/Kg infusion associated with pre/post-desmopressin measurements of plasma FVIII levels
| Study group | Role | What they receive |
|---|---|---|
| Variants Null | This group includes patients carrying a F8 variant with a major deleterious effect on the F8 gene (non-sense, intron 1 and 22 inversions, large deletions, small insertions/deletions leading to a frameshift and premature stop codon) Receives: Drug: Desmopressin | |
| Variants No Null | This group includes patients carrying a F8 variant with a mild effect on the F8 gene (missense, splice modification, small nucleotide deletion in the intron 13, and variant in the promoter) Receives: Drug: Desmopressin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the post-DDAVP FVIII peak in patients of the group "Null variants" vs "No Null variants"
Factor VIII levels measured with a chronometric one stage-assay 30 or 60 minutes after the DDAVP infusion
Measured: FVIII levels 30-60 minutes after the DDAVP infusion
Comparison of the post-DDAVP FVIII recovery in patients of the group "Null variants" vs "No Null variants"
Factor VIII levels measured with a chronometric one stage-assay before (basal FVIII) the DDAVP infusion and 30 or 60 minutes after (FVIII peak). The FVIII recovery = ratio FVIII peak / basal FVIII
Measured: FVIII levels before and 30-60 minutes after the DDAVP infusion
Comparison of the post-DDAVP FVIII clearance in patients of the group "Null variants" vs "No Null variants"
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Comparison of the post-DDAVP FVIII area under the curve (AUC) in patients of the group "Null variants" vs "No Null variants"
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Comparison of the post-DDAVP duration with FVIII normalized above 0.5 IU.dL-1 in patients of the group "Null variants" vs "No Null variants"
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Comparison of the post-DDAVP duration with FVIII normalized above 0.8 IU.dL-1 in patients of the group "Null variants" vs "No Null variants"
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Secondary outcomes (5)
Influence of the age on the post-DDAVP FVIII peak
factor VIII levels measured with a chronometric one stage-assay 30 or 60 minutes after the DDAVP infusion
Measured: FVIII levels 30-60 minutes after the DDAVP infusion
Influence of the age on the post-DDAVP FVIII recovery
Factor VIII levels measured with a chronometric one stage-assay before (basal FVIII) the DDAVP infusion and 30 or 60 minutes after (FVIII peak). The FVIII recovery = ratio FVIII peak / basal FVIII
Measured: FVIII levels before and 30-60 minutes after the DDAVP infusion
influence of the age on the post-DDAVP FVIII area under the curve (AUC)
Factor VIII levels measured with a chronometric one stage-assay before (basal FVIII) the DDAVP infusion and 30 or 60 minutes after (FVIII peak). The FVIII recovery = ratio FVIII peak / basal FVIII
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
influence of the age on the post-DDAVP duration with FVIII normalized above 0.5 IU.dL-1
factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
influence of the age on the post-DDAVP duration with FVIII normalized above 0.8 IU.dL-1
factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Measured: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2023
- Study start1 Jan 2022
- Primary completion1 Jan 2023
- Study completion1 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Carrier of Hemophilia AStudies 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
- Retrospective
- Enrolment
- 361 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Maladies hémorragiques de Bretagne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benoît Guillet, MD PhD, Principal investigator, University-hospital of Rennes and Inserm U1085 (IRSET), Faculty of Medicine, University Rennes 1
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06020456
- Sponsor's protocol ID
- 2023_GIDEHAC_01
- Acronym
- GIDEHAC
- Status last verified
- Aug 2023
- First submitted
- 28 Aug 2023
- Last updated
- 31 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known if there will be a plan to make IPD available
Publications
Seaman CD, Xavier F, Ragni MV. Hemophilia A (Factor VIII Deficiency). Hematol Oncol Clin North Am. 2021 Dec;35(6):1117-1129. doi: 10.1016/j.hoc.2021.07.006. Epub 2021 Aug 10.
PubMed 34389199Plug I, Mauser-Bunschoten EP, Brocker-Vriends AH, van Amstel HK, van der Bom JG, van Diemen-Homan JE, Willemse J, Rosendaal FR. Bleeding in carriers of hemophilia. Blood. 2006 Jul 1;108(1):52-6. doi: 10.1182/blood-2005-09-3879. Epub 2006 Mar 21.
PubMed 16551972Mannucci PM, Vicente V, Alberca I, Sacchi E, Longo G, Harris AS, Lindquist A. Intravenous and subcutaneous administration of desmopressin (DDAVP) to hemophiliacs: pharmacokinetics and factor VIII responses. Thromb Haemost. 1987 Dec 18;58(4):1037-9.
PubMed 3127916Leissinger C, Carcao M, Gill JC, Journeycake J, Singleton T, Valentino L. Desmopressin (DDAVP) in the management of patients with congenital bleeding disorders. Haemophilia. 2014 Mar;20(2):158-67. doi: 10.1111/hae.12254. Epub 2013 Aug 12.
PubMed 23937614van Galen KPM, d'Oiron R, James P, Abdul-Kadir R, Kouides PA, Kulkarni R, Mahlangu JN, Othman M, Peyvandi F, Rotellini D, Winikoff R, Sidonio RF. A new hemophilia carrier nomenclature to define hemophilia in women and girls: Communication from the SSC of the ISTH. J Thromb Haemost. 2021 Aug;19(8):1883-1887. doi: 10.1111/jth.15397.
PubMed 34327828Kaufmann JE, Vischer UM. Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP). J Thromb Haemost. 2003 Apr;1(4):682-9. doi: 10.1046/j.1538-7836.2003.00190.x.
PubMed 12871401Kaufmann JE, Oksche A, Wollheim CB, Gunther G, Rosenthal W, Vischer UM. Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J Clin Invest. 2000 Jul;106(1):107-16. doi: 10.1172/JCI9516.
PubMed 10880054Hews-Girard J, Rydz N, Lee A, Goodyear MD, Poon MC. Desmopressin in non-severe haemophilia A: Test-response and clinical outcomes in a single Canadian centre review. Haemophilia. 2018 Sep;24(5):720-725. doi: 10.1111/hae.13586. Epub 2018 Jul 13.
PubMed 30004154Kobrinsky NL, Watson CM, Cheang MS, Bishop AJ. Improved hemophilia A carrier detection by DDAVP stimulation of factor VIII. J Pediatr. 1984 May;104(5):718-24. doi: 10.1016/s0022-3476(84)80951-8.
PubMed 6425482Casonato A, Dannhauser D, Pontara E, Bertomoro A, Orazi B, Santarossa L, Zerbinati P, Girolami A. DDAVP infusion in haemophilia A carriers: different behaviour of plasma factor VIII and von Willebrand factor. Blood Coagul Fibrinolysis. 1996 Jul;7(5):549-53.
PubMed 8874865
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Genetic Factors Influencing the Factor VIII Response to Desmopressin in Carriers of Hemophilia A: the GIDEHAC Study
- ClinicalTrials.gov ID
- NCT06020456
- Acronym / sponsor ID
- GIDEHAC / 2023_GIDEHAC_01
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 361 participants (actual)
- Lead sponsor
- Groupe Maladies hémorragiques de BretagneUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 1 Apr 2023 (actual)
- First posted
- 31 Aug 2023 (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.
Hemophilia A (HA) is a rare X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII) affecting 1/5,000 males1. Carriers of HA are females carrying the pathogenic variant responsible for the familial HA at a heterozygous status. About 30% of HA carriers have low FVIII levels and can therefore have abnormal bleeding symptoms2,3. Such as males with moderate/mild HA, bleeding can be treated or prevented with either FVIII concentrates or desmopressin4,5. This drug acts as a vasopressin type 2-receptor (V2R) agonist that causes endothelial cells to rapidly secrete von Willebrand factor (VWF) and FVIII from Weibel-Palade bodies into the bloodstream6,7. However, the mechanism of action of post-DDAVP FVIII increase remains poorly understood in hemophilia A. 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.
The FVIII response profile to DDAVP in carriers appears quite similar to that seen in men with mild/moderate HA8-11. A post-DDAVP increase in the FVIII level of 2-4 fold the basal level is usually observed. This FVIII response presents an important inter-individual variation making it necessary to carry out a therapeutic test before its use for the anti-hemorrhagic treatment. The basal FVIII level logically conditions the intensity of the post-DDAVP FVIII peak. However, other factors influencing the post-DDAVP FVIII response are very likely. Unfortunately, few series describing the FVIII response to DDAVP in HA carriers have been reported to date and they included too small numbers of patients to precisely analyze the factors of variation in the post-DDAVP FVIII pharmacokinetics (PK). Candy et al did not find any difference depending on the severity of the pathogenic variants for HA or on the age11. However, this study was carried out in a cohort including only 17 patients, therefore too small for a reliable statistical analysis.
The GIDEHAC study (Genetic Influence of Desmopressin Efficacy in Hemophilia A Carriers) is a French study with the following objectives: the description of the post-DDAVP FVIII PK in a large retrospective cohort of HA carriers, the research of patients-related factors influencing this FVIII PK, and the building of predictive population- and Bayesian-based models.
Detailed description
The GIDEHAC study is a French observational, retrospective, and multicentric study performed in carriers of hemophilia A of any age who have received the intravenous desmopressin in their French Hemophilia Treatment Centers (HTC).
Objectives of the GIDEHAC study:
- Description of the post-desmopressin (DDAVP) FVIII pharmacokinetics (PK) in a large retrospective cohort of patients with mild/moderate HA,
- Research of patients-related factors influencing this FVIII PK,
- Building of predictive population- and Bayesian-based models
Inclusion criteria:
- Females at any ages with a confirmed diagnosis of HA carriers based on the F8 gene analysis,
- Patients having received DDAVP during the last 10 years that was associated with dosages of FVIII before and just after DDAVP,
- Factor VIII levels measurements realized at least 2 times during the therapeutic test, just before the DDAVP infusion and 30 or 60 minutes after.
Exclusion criteria:
- Patients with an anti-factor VIII inhibitor,
- Refusal to participate in the study,
- Unable to understand the study's French letter of non-opposition and information.
Description of the DDAVP therapeutic tests:
The procedure of the DDAVP therapeutic test was identical for all investigator centers as recommended by international and French guidelines. DDAVP was so always administered intravenously at a dose of 0.3-0.4 μg.kg-1 diluted in 50 mL of saline solution over 30 minutes. The required hemostatic parameters are FVIII levels before and at least 30 or 60 minutes after the DDAVP infusion. Subsequent FVIII measurements performed at T2h, T4h and T6h after the infusion are also recorded during the test.
Collected data:
All data collected in this study were issued from the medical files at the moment of the DDAVP therapeutic test. They include:
- FVIII activity levels measured with a one-stage clotting assay from plasmas collected in 0.109 M sodium citrate (fresh or stored at -80°C). These FVIII levels were measured just before and after the DDAVP infusion (until 24 hours if available),
- The pathogenic variant of the F8 gene responsible for the familial HA,
- Blood group,
- DDAVP doses,
- Von Willebrand factor levels during the DDAVP test,
- Age,
- Weight,
- FVIII levels measured during pregnancies,
- The degree of familial link if relatives are included in this study.
Pharmacokinetic analyses The following FVIII and VWF pharmacokinetic parameters are calculated using a compartmental approach with non-linear models at mixed effect (MONOLIX software, v2021, Lixsoft): basal FVIII and post-DDAVP FVIII peak (highest level measured after DDAVP administration), FVIII recovery (recFVIII = peak FVIII / basal FVIII), FVIII half-life (FVIII T1/2), FVIII clearance, FVIII area under the curve (FVIII AUC), and duration with FVIII ≥0.5 and 0.8 IU.dL-1.
Scores measuring the FVIII response to DDAVP
For qualitative assessment of the biological response to DDAVP, criteria previously reported by Stoof et al were used:
- The absolute response was either "complete" (peak FVIII ≥0.5 IU.mL-1), "partial" (FVIII ≥0.3 - <0.5 IU.mL-1) or "null" (FVIII <0.3 IU.mL-1).
- The relative response was defined as "complete" (recFVIII >3), "partial" (recFVIII ≥2 - <3) or "null" (recFVIII <2).
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Variants Null | – | Drug: DesmopressinThis group includes patients carrying a F8 variant with a major deleterious effect on the F8 gene (non-sense, intron 1 and 22 inversions, large deletions, small insertions/deletions leading to a frameshift and premature stop codon) |
| Variants No Null | – | Drug: DesmopressinThis group includes patients carrying a F8 variant with a mild effect on the F8 gene (missense, splice modification, small nucleotide deletion in the intron 13, and variant in the promoter) |
Who may qualify
- Ages
- 2 to 80 years
- Sex
- Female only
- Age groups
- Child, Adult, Older adult
- Study population
- The study includes carriers of hemophilia A of any age who had a desmopressin therapeutic test during the last 10 years, associated with FVIII levels measurements before/after desmopressin. All procedures of the desmopressin therapeutic tests comprised an intravenous infusion of 0.3-0.4 μg.kg-1 diluted in 50 mL of saline solution over 30 minutes, associated with FVIII levels measured before and at least 30 or 60 minutes after the desmopressin infusion. Subsequent measurements performed at T2h, T4h and T6h after the infusion are also recorded during the test. All the data collected in this study were issued from the medical files including: pre/post desmopressin FVIII and VWF levels, F8 mutation, severity of the familial hemophilia A blood group, desmopressin doses, age, and weight.
Key inclusion criteria (3 listed)
- Females at any ages with a formal diagnosis of HA carriers based on the F8 genetics,
- Patients having received DDAVP during the last 10 years that was associated with dosages of FVIII before and just after DDAVP,
- Factor VIII levels measurements realized at least 2 times during the therapeutic test, just before the DDAVP infusion and 30 or 60 minutes after.
Key exclusion criteria (3 listed)
- Patients with an anti-factor VIII inhibitor,
- Refusal to participate in the study,
- Unable to understand the study's French letter of non-opposition and information
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DesmopressinFor the 2 groups, all patients have received an intravenous DDAVP 0,3-0,4 µg/Kg infusion associated with pre/post-desmopressin measurements of plasma FVIII levels | Drug | Variants No Null, Variants Null |
Primary outcome
Comparison of the post-DDAVP FVIII peak in patients of the group "Null variants" vs "No Null variants"
Time frame: FVIII levels 30-60 minutes after the DDAVP infusion
Factor VIII levels measured with a chronometric one stage-assay 30 or 60 minutes after the DDAVP infusion
Comparison of the post-DDAVP FVIII recovery in patients of the group "Null variants" vs "No Null variants"
Time frame: FVIII levels before and 30-60 minutes after the DDAVP infusion
Factor VIII levels measured with a chronometric one stage-assay before (basal FVIII) the DDAVP infusion and 30 or 60 minutes after (FVIII peak). The FVIII recovery = ratio FVIII peak / basal FVIII
Comparison of the post-DDAVP FVIII clearance in patients of the group "Null variants" vs "No Null variants"
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Comparison of the post-DDAVP FVIII area under the curve (AUC) in patients of the group "Null variants" vs "No Null variants"
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Comparison of the post-DDAVP duration with FVIII normalized above 0.5 IU.dL-1 in patients of the group "Null variants" vs "No Null variants"
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
Comparison of the post-DDAVP duration with FVIII normalized above 0.8 IU.dL-1 in patients of the group "Null variants" vs "No Null variants"
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Factor VIII levels measured with a chronometric one stage-assay before and after DDAVP until 24h post-infusion
5 secondary outcomes
Influence of the age on the post-DDAVP FVIII peak
Time frame: FVIII levels 30-60 minutes after the DDAVP infusion
Influence of the age on the post-DDAVP FVIII recovery
Time frame: FVIII levels before and 30-60 minutes after the DDAVP infusion
influence of the age on the post-DDAVP FVIII area under the curve (AUC)
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
influence of the age on the post-DDAVP duration with FVIII normalized above 0.5 IU.dL-1
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
influence of the age on the post-DDAVP duration with FVIII normalized above 0.8 IU.dL-1
Time frame: Factor VIII levels were measured until 24 hours after the desmopressin infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
- Background: PubMed 34389199Seaman CD, Xavier F, Ragni MV. Hemophilia A (Factor VIII Deficiency). Hematol Oncol Clin North Am. 2021 Dec;35(6):1117-1129. doi: 10.1016/j.hoc.2021.07.006. Epub 2021 Aug 10.
- Background: PubMed 16551972Plug I, Mauser-Bunschoten EP, Brocker-Vriends AH, van Amstel HK, van der Bom JG, van Diemen-Homan JE, Willemse J, Rosendaal FR. Bleeding in carriers of hemophilia. Blood. 2006 Jul 1;108(1):52-6. doi: 10.1182/blood-2005-09-3879. Epub 2006 Mar 21.
- Background: PubMed 3127916Mannucci PM, Vicente V, Alberca I, Sacchi E, Longo G, Harris AS, Lindquist A. Intravenous and subcutaneous administration of desmopressin (DDAVP) to hemophiliacs: pharmacokinetics and factor VIII responses. Thromb Haemost. 1987 Dec 18;58(4):1037-9.
- Background: PubMed 23937614Leissinger C, Carcao M, Gill JC, Journeycake J, Singleton T, Valentino L. Desmopressin (DDAVP) in the management of patients with congenital bleeding disorders. Haemophilia. 2014 Mar;20(2):158-67. doi: 10.1111/hae.12254. Epub 2013 Aug 12.
- Background: PubMed 34327828van Galen KPM, d'Oiron R, James P, Abdul-Kadir R, Kouides PA, Kulkarni R, Mahlangu JN, Othman M, Peyvandi F, Rotellini D, Winikoff R, Sidonio RF. A new hemophilia carrier nomenclature to define hemophilia in women and girls: Communication from the SSC of the ISTH. J Thromb Haemost. 2021 Aug;19(8):1883-1887. doi: 10.1111/jth.15397.
- Background: PubMed 12871401Kaufmann JE, Vischer UM. Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP). J Thromb Haemost. 2003 Apr;1(4):682-9. doi: 10.1046/j.1538-7836.2003.00190.x.
- Background: PubMed 10880054Kaufmann JE, Oksche A, Wollheim CB, Gunther G, Rosenthal W, Vischer UM. Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J Clin Invest. 2000 Jul;106(1):107-16. doi: 10.1172/JCI9516.
- Background: PubMed 30004154Hews-Girard J, Rydz N, Lee A, Goodyear MD, Poon MC. Desmopressin in non-severe haemophilia A: Test-response and clinical outcomes in a single Canadian centre review. Haemophilia. 2018 Sep;24(5):720-725. doi: 10.1111/hae.13586. Epub 2018 Jul 13.
- Background: PubMed 6425482Kobrinsky NL, Watson CM, Cheang MS, Bishop AJ. Improved hemophilia A carrier detection by DDAVP stimulation of factor VIII. J Pediatr. 1984 May;104(5):718-24. doi: 10.1016/s0022-3476(84)80951-8.
- Background: PubMed 8874865Casonato A, Dannhauser D, Pontara E, Bertomoro A, Orazi B, Santarossa L, Zerbinati P, Girolami A. DDAVP infusion in haemophilia A carriers: different behaviour of plasma factor VIII and von Willebrand factor. Blood Coagul Fibrinolysis. 1996 Jul;7(5):549-53.
- Individual participant dataSharing planned: Undecided. It is not yet known if there will be a plan to make IPD available
Related trials for Carrier of Hemophilia A
RecruitingObservational study
Hemophilia A Research Program
Hemophilia A, Hemophilia A, Severe
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.
Benoît Guillet, MD PhD principal investigator
University-hospital of Rennes and Inserm U1085 (IRSET), Faculty of Medicine, University Rennes 1
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carrier of Hemophilia A and Desmopressin, run by Groupe Maladies hémorragiques de Bretagne at 12 sites in France.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the post-DDAVP FVIII peak in patients of the group "Null variants" vs "No Null variants" (time frame: FVIII levels 30-60 minutes after the DDAVP infusion). The study lists 6 primary outcomes in all. 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 NCT06020456, which also lists 10 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 31 Aug 2023.