EMBARGO : 1 September 2015 at 9:00 BST
The findings, presented at ESC Congress 2015 today, and published simultaneously in the New England Journal of Medicine (to be confirmed), “may seem disappointing but have the potential to dramatically change the way we investigate and treat CD going forward,” noted the study’s co-principal investigator Carlos Morillo MD, from McMaster University in Hamilton, Ontario, Canada.
“We demonstrated that benznidazole has significant antiparasitic activity but there was regional variability both in the parasitic response as well as progression of heart problems,” he explained.
“Recent data indicate that parasite persistence may play a pivotal role in the pathogenesis of chronic Chagas cardiomyopathy, but until now we did not know whether antiparasitic treatment could prevent this. Our results confirm that with the current treatment, significant reductions in parasite DNA detection can be achieved. The lack of benefit in reducing the progression of cardiomyopathy may have been related to strain susceptibility or insufficient long-term activity against the parasite,” he added.
BENEFIT (which stands for BENznidazole Evaluation For Interrupting Trypanosomiasis Trial) included 2,854 patients from 5 countries in Central and South America.
All patients had serologic evidence of the Trypanosoma cruzi parasite which causes Chagas, as well as electrocardiographic and other typical cardiac abnormalities characteristic of Chagas cardiomyopathy (CCM).
“The T-cruzi parasite is transmitted to humans by triatomine insects and is curable when treated early with antiparasitics. However, it is often not recognised at this stage and 30% - 40% of chronic infections lead to cardiomyopathy within 10-30 years,” explained Dr. Morillo.
The patients were randomised to treatment with placebo or benznidazole for 40 - 80 days, with the primary outcome of the study being a composite of all cause death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of pacemaker or cardiac defibrillator, cardiac transplantation, development of new heart failure, and stroke, or systemic or pulmonary thromboembolic events.
After an average follow-up of 5.4 years, the primary outcome occurred in a similar percentage of patients in the treatment and placebo arms (27.5% and 29.1% respectively; hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.81-1.07; P=0.31).
Parasite persistence was significantly reduced after treatment, compared to placebo (66.2% versus 33.5%), an effect that was not fully maintained after 5 years (46.7% versus 33.1% respectively (all P<0.0001).
Reduction in parasite DNA detection varied among participating countries with a significantly lower response observed in Colombia and El Salvador compared to other countries (odds ratio [OR] 1.33 and 0.96 at 2 and 5 or more years).
BENEFIT is the largest trial to date to examine the impact of benznidazole treatment in patients with CCM, said Dr. Morillo.
“The trial took 13 years from its inception to termination and built a large network of clinical investigators interested in this neglected disease. It has furthered our knowledge of the disease and response to trypanocidal therapy. Approximately 7 million people world wide are infected by T. cruzi and, given the favorable risk/benefit ratio observed in BENEFIT, treatment during the early stages of chronic Chagas infection should be strongly encouraged. The need to treat patients with established cardiomyopathy needs further research to determine whether different dosing and duration schemes as well as geographic susceptibility may in fact identify CCM patients that benefit from trypanocidal therapy.”
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