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Hemophilia AKADOAHNCT05804734

Vitamin K Antagonist Versus Direct Oral Anticoagulant Treatments in Hemophilia

An observational study of Hemophilia A and Hemophilia B, run by Groupe Maladies hémorragiques de Bretagne at 6 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Hemophilia is a rare X-linked bleeding disorder responsible for deficiency of coagulation factor VIII (FVIII) or IX (FIX). The main clinical manifestation is increased bleeding throughout the life which is directly correlated to the severity of the hemophilia, either mild (FVIII/FIX: 6-40), moderate (FVIII/FIX: 1-5%)… Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Vitamin K Antagonist - Drug
Type of treatment
Pill or oral medicine
How many people
54 participants
Where
6 sitesFrance
Study dates
1 Jun 2021to 31 Dec 2021
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 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The study includes only patients with hemophilia: cases who are patients having received an anticoagulant treatment (cases) for at least 6 months during the period 2112-2021, and controls without anticoagulant treatment cross-matched with cases on the age, the severity and type of hemophilia, and the HAS-BLED score. All the data collected in this study are issued from the medical files.

Who may be able to join

  • Cases :
  • Males at any ages with hemophilia of any severity and of any type,
  • Patients having received or receiving a long-term anticoagulant treatment (during at least 6 consecutive months) during the period from 2012 to 2021,
  • Regular follow-up in a hemophilia treatment center.
  • Controls : patients with hemophilia cross-matched with cases on:
  • Age (+/- 5 years),
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  • Hemophilia type (either A or B)
  • Hemophilia severity (for mild hemophilia: same basal factor level +/- 5%),
  • HAS-BLED score (same score +/- 1).

Who cannot join

  • Lost to medical follow-up,
  • Refusal to participate in the study,
  • Unable to understand the study's French letter of non-opposition and information.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

France6 sites
  • Hemophilia treatment center of Brest

    Brest, 29609

  • Hemophilia treatment center of caen

    Caen, 14033

  • Hemophilia treatment center of Le Mans

    Le Mans, 72037

  • Hemophilia treatment center of Nantes

    Nantes, 44093

  • Hemophilia treatment center of Rennes

    Rennes, 35033

  • Hemophilia treatment center of Rouen

    Rouen, 76000

Other trials in France

About this study

Hemophilia is a rare X-linked bleeding disorder responsible for deficiency of coagulation factor VIII (FVIII) or IX (FIX). The main clinical manifestation is increased bleeding throughout the life which is directly correlated to the severity of the hemophilia, either mild (FVIII/FIX: 6-40), moderate (FVIII/FIX: 1-5%), or severe (FVIII/FIX<1%). Thanks to new therapies and long-term specialized follow-up by hemophilia treatment centers (HTCs), the life expectancy of patients with hemophilia (PWH) has improved considerably, even reaching that of the general population (1).

Healthcare professionals are so more confronted to PWH with age-related pathologies, in particular cardiovascular pathologies such as atrial fibrillation, acute coronary syndromes or thromboembolic events (arterial or venous). It is now recommended in PWH that an anticoagulant treatment (AC) be prescribed as in the general population (2,3,4). The recently published COCHE study demonstrated a significantly increased risk of bleeding in PWH receiving antithrombotic treatment. This bleeding risk depended significantly on the type of antithrombotic treatment, which was higher for anticoagulant vs antiplatelet drugs, on basal levels of FVIII or FIX, and on the HAS-BLED score (5).

Nowadays in the general population, among anticoagulant drugs, direct oral anticoagulants (DOACs) are preferred to vitamin K antagonist (KVA), thanks to their reduced risk of bleeding particularly intracerebral bleeding and better anticoagulant stability over time (6). However, we do not yet know precisely whether DOACs could occupy the same place in the PWH population because of the lack of evidence-based data due to the very small number of these patients, although some authors already recommend them over KVA. The KADOAH study was therefore set up to try to provide initial elements for future recommendations. Its main objective was to compare the level of bleeding risk of PWH treated with VKA vs DOACs.

Read the detailed description

The KADOAH study is an observational, retrospective and multicenter case-control study conducted in Hemophilia Treatment Centers (HTC) of the French Grand-Ouest interregion including HTCs of Brest, Caen, Le Mans, Nantes, Rennes and Rouen.

Objectives of the KADOAH study are:

  • To compare the risk of bleeding events of 2 types of long-term anticoagulant treatment, vitamin K antagonists (VKA) versus Direct Oral Anticoagulants (DOAC), in patients with hemophilia,
  • To describe the different types of bleeding events that occur during anticoagulant treatments in patients with hemophilia,
  • To investigate for the influence of the HAS-BLED score on the risk of bleeding events in patients with hemophilia receiving a long-term anticoagulant treatment.

Inclusion criteria:

  • Cases :
  • Males at any ages with hemophilia of any severity and of any type,
  • Patients having received or receiving a long-term anticoagulant treatment (during at least 6 consecutive months) during the period from 2012 to 2021,
  • Regular follow-up in a hemophilia treatment center.
  • Controls cross-matched with cases on :
  • Age (+/- 5 years),
  • Hemophilia type (either A or B)
  • Hemophilia severity (for mild hemophilia: same basal factor level +/- 5%),
  • HAS-BLED score (same score +/- 1).

Exclusion criteria:

  • Lost to medical follow-up,
  • Refusal to participate in the study,
  • Unable to understand the study's French letter of non-opposition and information.

Collected data:

All data collected in this study were issued from the medical files at the moment of the inclusion in the study. They include:

  • The age,
  • The hemophilia's type,
  • The hemophilia's severity and last basal factor VIII or IX level,
  • The treatment with anticoagulant drug for cases including :
  • Type of drug (either VKA or DOAC)
  • Duration of treatments
  • Treatments dosages,
  • Compliance of treatments,
  • Indications,
  • If stopped prematurely, reasons for stopping.
  • The occurrence of severe bleeding events (SBE) following the ISTH definition (7):
  • The number of SBE per patient,
  • The types of SBE,
  • The treatment of SBE.
  • The HAS-BLED score calculated with the presence or absence of the following items:
  • High arterial pressure,
  • Abnormal renal and/or liver functions,
  • Hemorrhagic stroke,
  • Bleeding antecedent,
  • Age >65 years,
  • Treatments altering the hemostasis (out of the anticoagulants) and/or alcohol intoxication.
  • The CHA2DS-VASc score calculated with the presence or absence of the following items:
  • Cardiac insufficiency/left ventricular dysfunction,
  • High arterial pressure,
  • Age ≥ 75 years, or age = 65 - 74 years,
  • Diabetes,
  • History of thrombotic events (transient ischemic cerebral attack or stroke, venous thromboembolic events)
  • Associated treatment with a proton pomp inhibitor or other gastric protector,

Statistical analyses Descriptive characteristics were analyzed with median values, their 25-75% interquartile ranges (IQR) and minimum-maximum values (MIN-MAX), or mean values with standard deviation (SD). The Fisher's exact test will be performed to compare proportions in contingency tables and the t Student test to compare continuous variables. An approximate 95% confidence interval will be determined (95% CI) for every statistical analysis and a p-value <0.05 will be considered statistically significant. The GraphPad v7.0 (Prism Software Inc. San Diego CA) will be used to perform the statistical analyses.

Being tested
Vitamin K Antagonist - Drug
Keywords
Hemophilia A, Hemophilia B, Anticoagulant-induced Bleeding
Medical subject headings
Hemophilia A, Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vitamin K Antagonist - DrugDrug

    Also called direct oral anticoagulant

    Only clinical data (number and types of severe bleeding events, HAS-BLED score, CHA2DS2-VASc score) are collected during the follow-up:

    • For cases when they received an anticoagulant treatment and during the 12 months preceding this treatment,
    • For controls during the same periods of their cross-matched cases when reciving anticoagulant treatment.
Study groups in NCT05804734
Study groupRoleWhat they receive
CasesPatients with hemophilia receiving an anticoagulant treatment in the period 2012-2021
Receives: Drug: Vitamin K Antagonist - Drug
ControlsPatients with hemophilia cross-matched with cases on the age, the hemophilia's severity, the hemophilia's type, and the HAS-BLED score.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Comparison of the number of severe bleeding events occurring in patients with hemophilia receiving a vitamin K antagonist treatment versus patients with hemophilia receiving a direct oral anticoagulant treatment.

    Number of severe bleeding events

    Measured: All over the duration of the anticoagulant treatment in the period 2012-2021

Secondary outcomes (4)
  1. Comparison of the number of severe bleeding events occurring in patients with hemophilia receiving an anticoagulant treatment versus their cross-matched controls not receiving an anticoagulant treatment.

    Number of severe bleeding events

    Measured: All over the duration of the anticoagulant treatment in the period 2012-2021

  2. Description of the types of severe bleeding events occurring in patients with hemophilia receiving an anticoagulant treatment (either vitamin K antagonist or direct oral anticoagulant treatment).

    Types of bleeding

    Measured: All over the duration of the anticoagulant treatment in the period 2012-2021

  3. The influence of the HAS-BLED score on the risk of severe bleeding events in patients with hemophilia receiving an anticoagulant treatment.

    HAS-BLED score

    Measured: All over the duration of the anticoagulant treatment in the period 2012-2021

  4. The influence of a treatment with proton pomp inhibitor on the risk of gastrointerstinal bleeding events in patients with hemophilia receiving an anticoagulant treatment.

    Number of gastrointestinal bleeding

    Measured: All over the duration of the anticoagulant treatment in the period 2012-2021

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2023
  2. Study start1 Jun 2021
  3. Primary completion31 Dec 2021
  4. Study completion31 Dec 2021

Resources

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
Case-control
Time perspective
Retrospective
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05804734
Sponsor's protocol ID
2023_VKA-DOA_01
Acronym
KADOAH
Status last verified
Mar 2023
First submitted
27 Mar 2023
Last updated
7 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Andrade JG, Verma A, Mitchell LB, Parkash R, Leblanc K, Atzema C, Healey JS, Bell A, Cairns J, Connolly S, Cox J, Dorian P, Gladstone D, McMurtry MS, Nair GM, Pilote L, Sarrazin JF, Sharma M, Skanes A, Talajic M, Tsang T, Verma S, Wyse DG, Nattel S, Macle L; CCS Atrial Fibrillation Guidelines Committee. 2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Can J Cardiol. 2018 Nov;34(11):1371-1392. doi: 10.1016/j.cjca.2018.08.026.

    PubMed 30404743
  • Ferraris VA, Boral LI, Cohen AJ, Smyth SS, White GC 2nd. Consensus review of the treatment of cardiovascular disease in people with hemophilia A and B. Cardiol Rev. 2015 Mar-Apr;23(2):53-68. doi: 10.1097/CRD.0000000000000045.

    PubMed 25436468
  • Schutgens RE, van der Heijden JF, Mauser-Bunschoten EP, Mannucci PM. New concepts for anticoagulant therapy in persons with hemophilia. Blood. 2016 Nov 17;128(20):2471-2474. doi: 10.1182/blood-2016-07-727032. Epub 2016 Sep 26. No abstract available.

    PubMed 27670425
  • Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.

    PubMed 15842354
  • Darby SC, Kan SW, Spooner RJ, Giangrande PL, Hill FG, Hay CR, Lee CA, Ludlam CA, Williams M. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood. 2007 Aug 1;110(3):815-25. doi: 10.1182/blood-2006-10-050435. Epub 2007 Apr 19.

    PubMed 17446349
  • Guillet B, Cayla G, Lebreton A, Trillot N, Wibaut B, Falaise C, Castet S, Gautier P, Claeyssens S, Schved JF. Long-Term Antithrombotic Treatments Prescribed for Cardiovascular Diseases in Patients with Hemophilia: Results from the French Registry. Thromb Haemost. 2021 Mar;121(3):287-296. doi: 10.1055/s-0040-1718410. Epub 2020 Oct 24.

    PubMed 33099283
  • Gomez-Outes A, Terleira-Fernandez AI, Calvo-Rojas G, Suarez-Gea ML, Vargas-Castrillon E. Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups. Thrombosis. 2013;2013:640723. doi: 10.1155/2013/640723. Epub 2013 Dec 22.

    PubMed 24455237

Questions about this trial

What is this clinical trial studying?

An observational study of Hemophilia A and Hemophilia B, run by Groupe Maladies hémorragiques de Bretagne at 6 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 9 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 7 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 number of severe bleeding events occurring in patients with hemophilia receiving a vitamin K antagonist treatment versus patients with hemophilia receiving a direct oral anticoagulant treatment. (time frame: All over the duration of the anticoagulant treatment in the period 2012-2021). 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 NCT05804734, which also lists 7 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 7 Apr 2023.

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