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A Trial Testing Amiodarone in Chagas Cardiomiopathy (ATTACH)

Primary Purpose

Chagas Cardiomyopathy

Status

Unknown status

Phase

Phase 3

Locations

Colombia

Study Type

Interventional

Intervention

Amiodarone Hydrochloride

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for Chagas Cardiomyopathy focused on measuring Chagas disease, cardiomyopathy, amiodarone, clinical trial

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
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

Sites / Locations

Fundación Cardioinfantil - Instituto de CardiologíaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Amiodarone Hydrochloride

Placebo

Arm Description

Oral treatment for at least 6 months

Outcomes

Primary Outcome Measures

Positive PCR for Trypanosoma cruzi

Conventional (qualitative) Polymerase Chain Reaction. At least one positive result out of three tests at least one week apart from each other

Secondary Outcome Measures

Composite of clinical events

a) All-cause deaths; b) EKG-supported ventricular tachycardia or, c) Hospitalization for cardiac causes

Elements of the composite outcome of clinical events individually

Full Information

NCT ID

NCT03193749

First Posted

June 19, 2017

Last Updated

June 20, 2017

Sponsor

Fundación Cardioinfantil Instituto de Cardiología

Collaborators

Instituto de Corazón de Bucaramanga

1. Study Identification

Unique Protocol Identification Number

NCT03193749

Brief Title

A Trial Testing Amiodarone in Chagas Cardiomiopathy

Acronym

ATTACH

Official Title

A Trial Testing Amiodarone in Chagas Cardiomyopathy (ATTACH)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Unknown status

Study Start Date

June 12, 2017 (Actual)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundación Cardioinfantil Instituto de Cardiología

Collaborators

Instituto de Corazón de Bucaramanga

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chagas Cardiomyopathy

Keywords

Chagas disease, cardiomyopathy, amiodarone, clinical trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Matching placebo

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Amiodarone Hydrochloride

Arm Type

Experimental

Arm Description

Oral treatment for at least 6 months

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Oral treatment for at least 6 months

Intervention Type

Drug

Intervention Name(s)

Amiodarone Hydrochloride

Intervention Description

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

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

Matching placebo for tablets of 200 mg of Amiodarone

Primary Outcome Measure Information:

Title

Positive PCR for Trypanosoma cruzi

Description

Conventional (qualitative) Polymerase Chain Reaction. At least one positive result out of three tests at least one week apart from each other

Time Frame

6 months after starting treatment

Secondary Outcome Measure Information:

Title

Composite of clinical events

Description

a) All-cause deaths; b) EKG-supported ventricular tachycardia or, c) Hospitalization for cardiac causes

Time Frame

Up to study closure or 24 months after randomization (whichever comes first)

Title

Elements of the composite outcome of clinical events individually

Time Frame

Up to study closure or 24 months after randomization (whichever comes first)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

ATTACH will enroll individuals with positive serology for Trypanozoma cruzi and evidence of both structrural and rythm/conduction cardiac abnormalities, as defined by any of the following inclusion criteria 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Juan C Villar, MD, MSc, PhD

Phone

16672727

Ext

73200

jvillarc@cardioinfantil.org

First Name & Middle Initial & Last Name or Official Title & Degree

Eliana Vaquiro, RN, CCRN

Phone

16672727

Ext

73200

evaquiro@cardioinfantil.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan C Villar, MD, MSc, PhD

Organizational Affiliation

Department of Research, Fundación Cardioinfantil - Instituto de Cardiología

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Diego A Rodriguez, MD

Organizational Affiliation

Department of Cardiology, Fundación Cardioinfantil - Instituto de Cardiología

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fundación Cardioinfantil - Instituto de Cardiología

City

Bogotá

Country

Colombia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eliana Vaquiro, RN, CCRN

Phone

6672727

Ext

73200

evaquiro@cardioinfantil.org

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Upon submission of primary results, following requests of editors, by request to the steering committee

Citations:

PubMed Identifier

16928995

Citation

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.

Results Reference

background

PubMed Identifier

17339568

Citation

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.

Results Reference

background

PubMed Identifier

22591838

Citation

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.

Results Reference

background

PubMed Identifier

21078932

Citation

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.

Results Reference

background

PubMed Identifier

16451055

Citation

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.

Results Reference

background

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A Trial Testing Amiodarone in Chagas Cardiomiopathy

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