Trial record 2 of 87 for:    Open Studies | "Warfarin"

Therapeutic Equivalence Between Branded and Generic Warfarin Tablets in Brazil

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Federal University of São Paulo
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Carolina Gomes Freitas, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT02017197
First received: December 11, 2013
Last updated: May 24, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to assess whether the switch from branded to generic warfarin or between different generic warfarin tablets may cause fluctuation in the results of coagulation tests (International Normalized Rate, acronym INR) in patients, thus predisposing them to unnecessary risks.


Condition Intervention Phase
Atrial Fibrillation
Drug: Marevan®
Drug: generic warfarin #1
Drug: generic warfarin #2
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Therapeutic Equivalence Between Branded and Generic Warfarin Sodium Tablets in Adult Patients With Atrial Fibrillation in Brazil - Crossover Randomized Controlled Equivalence Trial

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • Mean change in INR with each generic formulation [ Time Frame: After four weeks with each formulation ] [ Designated as safety issue: Yes ]

    INR: International normalized ratio. The final analysis will not consider data from the run-in period (phase 1). INR will be assessed twice a month during the 15 weeks of study.

    Mean INR for each patient will be measured while using each generic formulation of warfarin; the baseline will be the mean INR during the use of the branded warfarin (Marevan®). Outcome will then be the mean difference between these two measurements.



Secondary Outcome Measures:
  • Mean change in PT with each generic formulation [ Time Frame: After four weeks with each formulation ] [ Designated as safety issue: Yes ]

    PT: prothrombin time. The final analysis will not consider data from the run-in period (phase 1). PT will be assessed twice a month during the 15 weeks of study.

    Mean PT for each patient will be measured while using each generic formulation of warfarin; the baseline will be the mean PT during the use of the branded warfarin (Marevan®). Outcome will then be the mean difference between these two measurements.


  • Incidence of thromboembolic events [ Time Frame: At weeks 7, 11 and 15 (i.e. at the end of phases 2, 3 and 4) ] [ Designated as safety issue: No ]
    Includes ischemic stroke (differential diagnosis with hemorrhagic stroke by tomography) and thromboembolism of viscera or extremities (diagnosed by acute symptoms and relevant diagnostic tests). The final analysis will not consider data from the run-in period (phase 1).

  • Time in therapeutic range (TTR) [ Time Frame: At weeks 7, 11 and 15 (i.e. at the end of phases 2, 3 and 4) ] [ Designated as safety issue: Yes ]
    TTR calculated by Rosendaal Method also known as linear interpolation method. The final analysis will not consider data from the run-in period (phase 1).

  • Incidence of bleeding events [ Time Frame: At weeks 7, 11 and 15 (i.e. at the end of phases 2, 3 and 4) ] [ Designated as safety issue: Yes ]

    Classified as major or minor bleeding events.

    Major: intracranial hemorrhage, fatal bleeding, bleeding resulting in hemoglobin loss equal to or greater than 2.0 g / L, hemorrhage requiring transfusion, bleeding in sensitive areas such as the retina or pericardium.

    Minor: all other bleeding.

    The final analysis will not consider data from the run-in period (phase 1).



Other Outcome Measures:
  • Compliance with treatment [ Time Frame: Monthly (from the beginning of treatment up to week 15). ] [ Designated as safety issue: No ]
    Performed by counting of returned pills


Estimated Enrollment: 60
Study Start Date: May 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sequence A

Phase 1 (3-week run-in period): Marevan®

Phase 2 (4 weeks): Marevan®

Phase 3 (4 weeks): generic warfarin #1

Phase 4 (4 weeks): generic warfarin #2

Drug: Marevan®
Branded warfarin sodium tablets (manufacturer União Química Farmacêutica Nacional S/A, Brazil) by mouth; dose adjusted according to INR and medical judgement.
Other Name: warfarin
Drug: generic warfarin #1
Generic warfarin sodium tablets, manufacturer (União Química Farmacêutica Nacional S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Drug: generic warfarin #2
Generic warfarin sodium tablets, manufacturer (Laboratório Teuto Brasileiro S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Sequence B

Phase 1 (3-week run-in period): generic warfarin #1

Phase 2 (4 weeks): generic warfarin #1

Phase 3 (4 weeks): Marevan®

Phase 4 (4 weeks): generic warfarin #2

Drug: Marevan®
Branded warfarin sodium tablets (manufacturer União Química Farmacêutica Nacional S/A, Brazil) by mouth; dose adjusted according to INR and medical judgement.
Other Name: warfarin
Drug: generic warfarin #1
Generic warfarin sodium tablets, manufacturer (União Química Farmacêutica Nacional S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Drug: generic warfarin #2
Generic warfarin sodium tablets, manufacturer (Laboratório Teuto Brasileiro S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Sequence C

Phase 1 (3-week run-in period): generic warfarin #1

Phase 2 (4 weeks): generic warfarin #1

Phase 3 (4 weeks): generic warfarin #2

Phase 4 (4 weeks): Marevan®

Drug: Marevan®
Branded warfarin sodium tablets (manufacturer União Química Farmacêutica Nacional S/A, Brazil) by mouth; dose adjusted according to INR and medical judgement.
Other Name: warfarin
Drug: generic warfarin #1
Generic warfarin sodium tablets, manufacturer (União Química Farmacêutica Nacional S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Drug: generic warfarin #2
Generic warfarin sodium tablets, manufacturer (Laboratório Teuto Brasileiro S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Sequence D

Phase 1 (3-week run-in period): Marevan®

Phase 2 (4 weeks): Marevan®

Phase 3 (4 weeks): generic warfarin #2

Phase 4 (4 weeks): generic warfarin #1

Drug: Marevan®
Branded warfarin sodium tablets (manufacturer União Química Farmacêutica Nacional S/A, Brazil) by mouth; dose adjusted according to INR and medical judgement.
Other Name: warfarin
Drug: generic warfarin #1
Generic warfarin sodium tablets, manufacturer (União Química Farmacêutica Nacional S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Drug: generic warfarin #2
Generic warfarin sodium tablets, manufacturer (Laboratório Teuto Brasileiro S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Sequence E

Phase 1 (3-week run-in period): generic warfarin #2

Phase 2 (4 weeks): generic warfarin #2

Phase 3 (4 weeks): Marevan®

Phase 4 (4 weeks): generic warfarin #1

Drug: Marevan®
Branded warfarin sodium tablets (manufacturer União Química Farmacêutica Nacional S/A, Brazil) by mouth; dose adjusted according to INR and medical judgement.
Other Name: warfarin
Drug: generic warfarin #1
Generic warfarin sodium tablets, manufacturer (União Química Farmacêutica Nacional S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Drug: generic warfarin #2
Generic warfarin sodium tablets, manufacturer (Laboratório Teuto Brasileiro S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Sequence F

Phase 1 (3-week run-in period): generic warfarin #2

Phase 2 (4 weeks): generic warfarin #2

Phase 3 (4 weeks): generic warfarin #1

Phase 4 (4 weeks): Marevan®

Drug: Marevan®
Branded warfarin sodium tablets (manufacturer União Química Farmacêutica Nacional S/A, Brazil) by mouth; dose adjusted according to INR and medical judgement.
Other Name: warfarin
Drug: generic warfarin #1
Generic warfarin sodium tablets, manufacturer (União Química Farmacêutica Nacional S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.
Drug: generic warfarin #2
Generic warfarin sodium tablets, manufacturer (Laboratório Teuto Brasileiro S/A, Brazil), by mouth; dose adjusted according to INR and medical judgement.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of nonvalvular atrial fibrillation by electrocardiogram and echocardiography;
  • CHA2DS2VASc score equal to or greater than 1;
  • already in use of warfarin;
  • signing of Informed Consent Form.

Exclusion Criteria:

  • patients with contraindications to the use of anticoagulants (patients either taking other anticoagulants, or with active bleeding, or hypersensitive to warfarin or with ulcers);
  • women of childbearing age, pregnant or breastfeeding;
  • patients with thrombocytopenia;
  • patients with hepatic or renal impairment;
  • patients with a history of bleeding episodes due to congenital deficiency of coagulation factors;
  • patients enrolled in another trial;
  • patients not achieving at least 70% TTR in the run-in period
  • patients initiating treatment with drugs with either moderate or major interactions or which are contraindicated when used concomitantly with warfarin, according to our list (Annex I).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02017197

Contacts
Contact: Carolina Gomes Freitas, PharmD +551155764203 carolina.freitas@unifesp.br

Locations
Brazil
Hospital São Paulo/Hospital Universitário da UNIFESP (University Hospital of UNIFESP) Recruiting
São Paulo, Brazil, 04024-002
Contact: Carolina Gomes Freitas, BPharm    +551155752970    carolina.freitas@unifesp.br   
Principal Investigator: Carolina Gomes Freitas, PharmD         
Sponsors and Collaborators
Federal University of São Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Carolina Gomes Freitas, PharmD Federal University of Sao Paulo (UNIFESP)
  More Information

No publications provided

Responsible Party: Carolina Gomes Freitas, Graduate student (masters), Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT02017197     History of Changes
Other Study ID Numbers: RCT 01 GW, U1111-1155-4833
Study First Received: December 11, 2013
Last Updated: May 24, 2014
Health Authority: Brazil: Ethics Committee

Keywords provided by Federal University of São Paulo:
Therapeutic Equivalency
Warfarin
Drugs, Generic
Anticoagulants
Anticoagulants [Pharmacological Action]
Coumarins

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014