Therapeutic equivalence between branded and generic warfarin sodium in atrial fibrillation adult patients in Brazil: crossover randomized clinical trial

• Grant number: 13/22618-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2014
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Álvaro Nagib Atallah
• Grantee: Álvaro Nagib Atallah
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Carolina Gomes Freitas

Abstract

Objective: To assess, by the average INR (international normalized ratio), therapeutic equivalence between branded and generic warfarin sodium in patients with atrial fibrillation in Brazil. Methods: crossover randomized controlled clinical trial. It will be used the branded warfarin sodium (Marevan®, União Química/Farmoquímica, referred as R) and both generic formulations (União Química Farmacêutica Nacional S/A and Laboratório Teuto Brasileiro S/A, respectively G1 and G2) available in the Brazilian market in October 2013. Sixty patients will be randomized to the predetermined sequences RRG1G2, G1G1RG2, G1G1G2R, RRG2G1, G2G2RG1, G2G2G1R and have INR collected weekly to detect through paired Student's t-test a 0,49 fluctuation in the mean INR when in use of the different formulations (±=5% and ²=10%). Inclusion criteria will be: nonvalvular atrial fibrillation diagnosis; plus indication for warfarin through CHA2DS2VASc score e1; plus current use of warfarin; plus age e18 years. Exclusion criteria: contraindication for anticoagulant use; pregnant, breastfeeding or childbearing age women; patients with thrombocytopenia, or hepatic or renal failure; patients with a history of bleeding episodes due to congenital deficiency of coagulation factors; patients not meeting a minimum of 70% of time in therapeutic range (TTR) in the run-in period; patients initiating treatment with drugs contraindicated or that interact moderate to severely when used at the same time as warfarin. Prothrombin time, TTR, compliance with treatment, incidence of bleeding and thromboembolic events will also be assessed as secondary outcomes. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREITAS, CAROLINA GOMES; WALSH, MICHAEL; ATALLAH, ALVARO NAGIB. Design and rationale for the WARFA trial: a randomized controlled cross-over trial testing the therapeutic equivalence of branded and generic warfarin in atrial fibrillation patients in Brazil. BMC CARDIOVASCULAR DISORDERS, v. 17, JUN 7 2017. (13/22618-6)

GOMES FREITAS, CAROLINA; WALSH, MICHAEL; COUTINHO, ENIA LUCIA; VINCENZO DE PAOLA, ANGELO AMATO; ATALLAH, ALVARO NAGIB. Examining therapeutic equivalence between branded and generic warfarin in Brazil: The WARFA crossover randomized controlled trial. PLoS One, v. 16, n. 4, p. 14-pg., 2021-04-01. (13/22618-6)

GOMES FREITAS, CAROLINA; WALSH, MICHAEL; COUTINHO, ENIA LUCIA; VINCENZO DE PAOLA, ANGELO AMATO; ATALLAH, ALVARO NAGIB. xamining therapeutic equivalence between branded and generic warfarin in Brazil: The WARFA crossover randomized controlled tria. PLoS One, v. 16, n. 4, APR 1 2021. (13/22618-6)