ABSTRACT
BACKGROUND: Cardiac complications, including heart failure and arrhythmias, are the leading causes of disability and death in Chagas disease (CD). CD, caused by the Trypanosoma cruzi parasite, afflicts 7 million people in Latin America, and its incidence is increasing in non-endemic countries due to migration. The cardiac involvement is explained by parasite-dependent, immune-mediated myocardial injury, microvascular abnormalities, and ischemia. Current treatment of early CD includes the administration of nifurtimox and benznidazole. However, their efficacy is low in the chronic phase and may induce severe adverse events, forcing therapy to halt. Therefore, finding innovative approaches to treat this life-threatening tropical disease is of utmost importance. Thus, improving the efficacy of the current antichagasic drugs by modifying the inflammatory response would render the current treatment more effective. It has been reported that, in mice, simvastatin decreases cardiac inflammation and endothelial activation, and improves cardiac function, effects that require clinical confirmation. OBJECTIVE: The study aims to analyze whether two doses of Atorvastatin, administered after CD treatment is completed, are safe and more efficacious than the antiparasitic drugs alone in reducing general inflammation and improving endothelial and cardiac functions in a proof-of-concept, placebo-controlled phase II trial. METHODS: 300 subjects will be recruited from four Chilean hospitals with an active Program for the Control of Chagas Disease. 40 or 80 mg/day of atorvastatin or placebo will be administered after completion of the antichagasic therapy. The patients will be followed up for 12 months. Efficacy will be determined by measuring changes in plasma levels of anti-inflammatory and pro-inflammatory cytokines, soluble cell adhesion molecules, BNP, and cTnT. Also, the resting 12-lead ECG and a 2D-echocardiogram will be obtained to evaluate cardiac function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04984616.
Subject(s)
Chagas Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Nitroimidazoles , Trypanocidal Agents , Trypanosoma cruzi , Atorvastatin/therapeutic use , Chagas Disease/drug therapy , Chagas Disease/parasitology , Clinical Trials, Phase II as Topic , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/drug therapy , Inflammation/chemically induced , Multicenter Studies as Topic , Persistent Infection , Randomized Controlled Trials as Topic , Trypanocidal Agents/therapeutic use , Trypanocidal Agents/pharmacology , HumansABSTRACT
Trypanosoma cruzi transplacental infection represents a serious public health concern in all the countries like Chile where recent success of insecticide spraying programs eliminated the vector. Because children infected with T. cruzi are usually asymptomatic, a study was designed including infected mothers and their children. The study was conducted for three years to establish diagnostic, treatment, and clinical observations variables. Mothers were tested for T. cruzi IgG, and the new born were examined for parasite DNA using PCR amplification. They were treated with nifurtimox and it was 100% effective, confirmed by successive PCR tests. It has been determined that there are 800 to 1000 new cases a year of transplacental Chagas' disease in Chile. This level of infection in the population should justify the establishment of a control and follow-up program for transplacental Chagas' disease.
