Vitamin K Antagonist Versus Direct Oral Anticoagulant Treatments in Hemophilia

NCT05804734 | Completed DMC FDA Drug

• 1 other identifier: 2023_VKA-DOA_01
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 6

Brief 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%), 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.

Conditions

Hemophilia A; Hemophilia B; Anticoagulant-induced Bleeding

Keywords

Hemophilia A; Hemophilia B; Anticoagulant-induced Bleeding

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (4)

• 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.

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

• 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).

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

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

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

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

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

Study Arms (2)

Cases

Patients with hemophilia receiving an anticoagulant treatment in the period 2012-2021

Drug: Vitamin K Antagonist - Drug

Controls

Patients with hemophilia cross-matched with cases on the age, the hemophilia's severity, the hemophilia's type, and the HAS-BLED score.

Interventions

Vitamin K Antagonist - Drug DRUG

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.

Also known as: direct oral anticoagulant

Cases

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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),
• Hemophilia type (either A or B)
• Hemophilia severity (for mild hemophilia: same basal factor level +/- 5%),
• HAS-BLED score (same score +/- 1).

You may not qualify if:

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

Sponsors & Collaborators

• Groupe Maladies hémorragiques de Bretagne: lead

Study Sites (6)

Hemophilia treatment center of Brest

Brest, 29609, France

Location

Hemophilia treatment center of caen

Caen, 14033, France

Location

Hemophilia treatment center of Le Mans

Le Mans, 72037, France

Location

Hemophilia treatment center of Nantes

Nantes, 44093, France

Location

Hemophilia treatment center of Rennes

Rennes, 35033, France

Location

Hemophilia treatment center of Rouen

Rouen, 76000, France

Location

Related Publications (7)

• 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.

  PMID: 30404743 BACKGROUND

• 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.

  PMID: 25436468 BACKGROUND

• 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.

  PMID: 27670425 BACKGROUND

• 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.

  PMID: 15842354 BACKGROUND

• 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.

  PMID: 17446349 RESULT

• 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.

  PMID: 33099283 RESULT

• 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.

  PMID: 24455237 RESULT

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Interventions

N(4)-oleylcytosine arabinoside

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Benoît GUILLET, MD PhD

  University hospital of rennes, France

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2023
• First Posted: April 7, 2023
• Study Start: June 1, 2021
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: April 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)