NCT04984616: ATOCHA

Atorvastatin on Inflammation and Cardiac Function in Chronic Chagas Disease

Terminated Phase 2 Last updated 19 September 2024

What this trial tests

Phase 2 trial testing 40 mg Atorvastatin/day for 120 days P.O. in Chronic Chagas Disease in 300 participants. Terminated before completion.

Timeline

12 October 2021

Primary endpoint
31 March 2024

1 April 2024

Quick facts

Lead sponsor	Juan D. Maya
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	300
Start date	12 October 2021
Primary completion	31 March 2024
Estimated completion	1 April 2024
Sites	4 locations across Chile

Drugs / interventions tested

• 40 mg Atorvastatin/day for 120 days P.O. — full drug profile →
• Atorvastatin 80 — full drug profile →
• Placebo

Conditions studied

• Chronic Chagas Disease — all drugs for Chronic Chagas Disease →

Sponsor

Juan D. Maya — full company profile →

Who can join

Adults 18 to 50, any sex, with Chronic Chagas Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Chagas Disease, caused by the parasite Trypanosoma cruzi afflicts 7 million people in Latin America, and due to migration, abroad. The diagnosis lies in clinical suspicion and serologic detection of antibodies. Cardiac evaluation is essential because complications, including heart failure and arrhythmias, are the main causes of disability and death. Heart involvement is explained by a parasite-dependent, immune-mediated myocardial and microvascular injuries.

Current treatment includes the administration of nifurtimox or benznidazole, although in the chronic phase their efficacy is low and may induce severe adverse events, forcing the suspension of the therapy. Therefore, finding innovative approaches to improve the efficacy of the current antichagasic drugs by modifying the inflammatory response would render the current treatment more effective.

Pre-clinical evidence supports the idea that the cholesterol-lowering statin drugs, such as atorvastatin, may contribute to decrease cardiac inflammation, reduce endothelial activation, and improve cardiac function. Atorvastatin therapeutic and safety profiles are well known, as is its mechanism of action, shared by the other members of the statin class.

This trial aims at evaluating whether atorvastatin, in combination with antichagasic therapy, is safe and more efficacious in reducing general inflammation than an antiparasitic therapy alone, by improving endothelial and cardiac functions.

This proof-of-concept trial will be double-blinded, randomized, and multicentered with a phase II design. To achieve this aim, it will be evaluated the efficacy of the combination of atorvastatin and antichagasic therapy (nifurtimox or benznidazole) to reduce inflammatory cytokine plasma levels, soluble endothelial cell adhesion molecules, and confirm the improvement of the cardiac function by electrocardiogram and two-dimensional echocardiogram.

The trial will set the safety and tolerability of the combination of atorvastatin with antichagasic therapy by monitoring the incidence of adverse events and discontinuation of the therapy.

This trial will be conducted with a sample size of 300 adult patients in four hospitals located in Santiago and Valparaiso, Chile.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Molecular and Immunomodulatory Mechanisms of Statins in Inflammation and Cancer Therapeutics with Emphasis on the NF-κB, NLRP3 Inflammasome, and Cytokine Regulatory Axes.
   Khan S, Huda B, Bhurka F, Patnaik R, et al · · 2025 · cited 7× · PMID 40943351 · DOI 10.3390/ijms26178429
2. Resveratrol and Curcumin for Chagas Disease Treatment-A Systematic Review.
   Imperador CHL, Scarim CB, Bosquesi PL, Lopes JR, et al · · 2022 · cited 4× · PMID 35631435 · DOI 10.3390/ph15050609
3. Effect of statins on inflammation and cardiac function in patients with chronic Chagas disease: A protocol for pathophysiological studies in a multicenter, placebo-controlled, proof-of-concept phase II trial.
   Campos-Estrada C, Urarte E, Denegri M, Villalón L, et al · · 2023 · cited 3× · PMID 36638112 · DOI 10.1371/journal.pone.0280335