A Trial Testing Amiodarone in Chagas Cardiomiopathy

NCT ID: NCT03193749

Last Updated: 2017-06-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-12
• Study Completion Date: 2020-12-31

Brief Summary

Purpose:

The ATTACH trial, as currently designed, will primarily test whether a treatment with Amiodarone for at least 6 months has a trypanocidal effect among individuals with mild-to-moderate Chronic Chagas Cardiomyopathy. A secondary goal will be to confirm, in this population, a clinical benefit from this treatment (in terms of reducing mortality or cardiac arrhythmic events), and to explore whether a potential trypanocidal effect is associated with a clinical benefit.

Detailed Description

Investigators currently plan to enroll over 200 participants in Bogotá and Bucaramanga, Colombia. Such sample size will provide 82% of statistical power to detect at least a 30% relative reduction in the primary outcome. This is assuming that at least 75% of untreated participants will test positive at least once after three qualitative PCR assays for Trypanosoma cruzi during the 6th month after randomization (allowing for up to 10% losses to follow up and treatment adherence over 90%).

ATTACH is currently seeking collaborating centers internationally. The current funding structure will allow to test study hypothesis on trypanocidal effect, whereas data on clinical effects will be exploratory. Investigators expect to increase the sample size to at least 600 participants in order to a) enhance geographical variability/generalizability for the primary results and b) to achieve enough statistical power to test the hypothesis on clinical impact.

New centers are welcome to join this protocol, either as a placebo-controlled or as a pragmatic, open label trial. These centers will be working with the central coordination with their own funding/logistic capabilities. In the open label protocol, eligible, consenting participants will be randomly prescribed or not to Amiodarone. As assessing clinical impact will be the priority, new centers are not required to have on-site PCR capabilities. These centers are encouraged to store blood samples for PCR testing elsewhere later, if possible.

See details on eligibility, interventions and outcome measures below

Conditions

Chagas Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amiodarone Hydrochloride

Oral treatment for at least 6 months

Group Type: EXPERIMENTAL

Amiodarone Hydrochloride

Intervention Type: DRUG

Starting (loading) dose 400 mg PO once a day for 10 days. Maintainance dose 200 mg PO once a day for at least 6 months, up to 24 months

Placebo

Oral treatment for at least 6 months

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Matching placebo for tablets of 200 mg of Amiodarone

Interventions

Amiodarone Hydrochloride

Starting (loading) dose 400 mg PO once a day for 10 days. Maintainance dose 200 mg PO once a day for at least 6 months, up to 24 months

Intervention Type: DRUG

Placebo Oral Tablet

Matching placebo for tablets of 200 mg of Amiodarone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Structural cardiac abnormality (at least one):

• NTpro-BNP values >125 ng/ml, or BNP values > 50 ng/ml
• Left ventricular ejection fraction (LVEF) <50% or left diastolic diameter > 5.5 cm
• Symptoms of heart failure, or one episode of acute heart failure over the last 12 months

2. Rrythm/conduction cardiac abnormality (at least one)

• EKG monitoring showing 10 or more VPBs/hour or ventricular Tachycardia
• EKG showing left anterior hemiblockade or right bundle branch blocakde
• Use of a cardiac stimulation device as treatment for A-V block or Sinus node dysfunction

The protocol allows concurrent treatments for the condition (e.g. beta-blockers, ACE inhibitors, etc.) other than Amiodarone. Individuals meeting the above eligibility criteria who have previously received trypanocidal therapy (e.g. Benznidazole or Nifurtimox) can still be included, as long as they prove to be PCR positive for T. cruzi at enrollment. Co-intervention with these agents during the study will also be allowed, as per physician's judgment, either as open label treatment, or as part of another study not involving Amiodarone.

Exclusion Criteria

• LVEF < 30% or NYHA Class III-IV
• Medical prescription with chronic use of Amiodarone
• Pregancy (currently, or planned in the following 2 years), or childbearing age without reliable birth control
• Heart rate < 50 or AV blockade without treatment with cardiac stimulation device
• Contraindication for Amiodarone as per treating physician (e.g. because of long QT syndrome, thyroid disease, interstitial lung disease)
• Atrial fibrillation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Corazón de Bucaramanga

UNKNOWN

Sponsor Role: collaborator

Fundación Cardioinfantil Instituto de Cardiología

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan C Villar, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Research, Fundación Cardioinfantil - Instituto de Cardiología

Diego A Rodriguez, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology, Fundación Cardioinfantil - Instituto de Cardiología

Locations

Fundación Cardioinfantil - Instituto de Cardiología

Bogotá, , Colombia

Site Status: RECRUITING

Countries

Colombia

Central Contacts

Juan C Villar, MD, MSc, PhD

Role: CONTACT

jvillarc@cardioinfantil.org

16672727 ext. 73200

Eliana Vaquiro, RN, CCRN

Role: CONTACT

evaquiro@cardioinfantil.org

16672727 ext. 73200

Facility Contacts

Eliana Vaquiro, RN, CCRN

Role: primary

evaquiro@cardioinfantil.org

6672727 ext. 73200

References

Rassi A Jr, Rassi A, Little WC, Xavier SS, Rassi SG, Rassi AG, Rassi GG, Hasslocher-Moreno A, Sousa AS, Scanavacca MI. Development and validation of a risk score for predicting death in Chagas' heart disease. N Engl J Med. 2006 Aug 24;355(8):799-808. doi: 10.1056/NEJMoa053241.

Reference Type: BACKGROUND

PMID: 16928995 (View on PubMed)

Rassi A Jr, Rassi A, Rassi SG. Predictors of mortality in chronic Chagas disease: a systematic review of observational studies. Circulation. 2007 Mar 6;115(9):1101-8. doi: 10.1161/CIRCULATIONAHA.106.627265.

Reference Type: BACKGROUND

PMID: 17339568 (View on PubMed)

Veiga-Santos P, Barrias ES, Santos JF, de Barros Moreira TL, de Carvalho TM, Urbina JA, de Souza W. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents. 2012 Jul;40(1):61-71. doi: 10.1016/j.ijantimicag.2012.03.009. Epub 2012 May 14.

Reference Type: BACKGROUND

PMID: 22591838 (View on PubMed)

Adesse D, Azzam EM, Meirelles Mde N, Urbina JA, Garzoni LR. Amiodarone inhibits Trypanosoma cruzi infection and promotes cardiac cell recovery with gap junction and cytoskeleton reassembly in vitro. Antimicrob Agents Chemother. 2011 Jan;55(1):203-10. doi: 10.1128/AAC.01129-10. Epub 2010 Nov 15.

Reference Type: BACKGROUND

PMID: 21078932 (View on PubMed)

Benaim G, Sanders JM, Garcia-Marchan Y, Colina C, Lira R, Caldera AR, Payares G, Sanoja C, Burgos JM, Leon-Rossell A, Concepcion JL, Schijman AG, Levin M, Oldfield E, Urbina JA. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem. 2006 Feb 9;49(3):892-9. doi: 10.1021/jm050691f.

Reference Type: BACKGROUND

PMID: 16451055 (View on PubMed)

Other Identifiers

277872553480

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

880-2015

Identifier Type: -

Identifier Source: org_study_id