A Trial Testing Amiodarone in Chagas Cardiomiopathy

Study Overview
=================
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

Official Title
-----------------
A Trial Testing Amiodarone in Chagas Cardiomyopathy (ATTACH)

Conditions
-----------------
Chagas Cardiomyopathy

Intervention / Treatment
-----------------
* Drug: Amiodarone Hydrochloride
* Drug: Placebo Oral Tablet


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiodarone Hydrochloride<br>Oral treatment for at least 6 months | Drug: Amiodarone Hydrochloride<br>* 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<br>|
| Placebo Comparator: Placebo<br>Oral treatment for at least 6 months | Drug: Placebo Oral Tablet<br>* Matching placebo for tablets of 200 mg of Amiodarone<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months after starting treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of clinical events | a) All-cause deaths; b) EKG-supported ventricular tachycardia or, c) Hospitalization for cardiac causes | Up to study closure or 24 months after randomization (whichever comes first) | 
| Elements of the composite outcome of clinical events individually |  | Up to study closure or 24 months after randomization (whichever comes first) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chagas disease, cardiomyopathy, amiodarone, clinical trial