A Trial Testing Amiodarone in Chagas Cardiomiopathy (ATTACH)

Fundación Cardioinfantil Instituto de Cardiología

Status and phase: Unknown; Phase 3

Conditions: Chagas Cardiomyopathy

Treatments: Drug: Placebo Oral Tablet; Drug: Amiodarone Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03193749

277872553480 (Other Grant/Funding Number)

880-2015

Details and patient eligibility

About

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.

Full 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

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups, including a placebo group

Amiodarone Hydrochloride

Experimental group

Description:

Oral treatment for at least 6 months

Treatment:

Drug: Amiodarone Hydrochloride

Placebo

Placebo Comparator group

Description:

Oral treatment for at least 6 months

Treatment:

Drug: Placebo Oral Tablet