Randomized trial of benznidazole for chronic chagas' cardiomyopathy

New England Journal of Medicine

Volumn 373, Issue 14, 2015, Pages 1295-1306

  Morillo, C A ^a   Marin Neto, J A ^b   Avezum, A ^c   Sosa Estani, S ^f   Rassi, A ^d   Rosas, F ^g   Villena, E ^f   Quiroz, R ⁱ   Bonilla, R ^k   Britto, C ^e   Guhl, F ^h   Velazquez, E ^j   Bonilla, L ^a   Meeks, B ^a   Rao Melacini, P ^a   Pogue, J ^a   Mattos, A ^c   Lazdins, J ^l   Connolly, S J ^a   Yusuf, S ^a  

^a MCMASTER UNIVERSITY   (Canada)

^b Cardiology Division Internal Medicine Department Medical School of Riberao Preto   (Canada)

^c INSTITUTO DANTE PAZZANESE DE CARDIOLOGIA   (Brazil)

^d Hospital do Corao Anis Rassi   (Brazil)

^e INSTITUTO OSWALDO CRUZ   (Brazil)

^f National Institute for the Production of Biologicals   (Argentina)

^g Fundacion Clinica Abood Shaio   (Colombia)

^h UNIVERSIDAD DE LOS ANDES   (Colombia)

ⁱ FUNDACIÓN CARDIOVASCULAR DE COLOMBIA   (Colombia)

^j Programa Chagas Hospital Eduardo Eguia   (United States)

^k Hospital Nacional Rosales   (El Salvador)

^l Neglected Tropical Diseases   (Switzerland)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BENZNIDAZOLE; PLACEBO; ANTITRYPANOSOMAL AGENT; NITROIMIDAZOLE DERIVATIVE;

ADULT; ARGENTINA; ARTICLE; BOLIVIA; BRAZIL; CEREBROVASCULAR ACCIDENT; CHAGAS DISEASE; CHRONIC DISEASE; COLOMBIA; CONTROLLED STUDY; DETERIORATION; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; EL SALVADOR; FEMALE; FOLLOW UP; GASTROINTESTINAL SYMPTOM; GEOGRAPHY; HEART ARREST; HEART FAILURE; HEART TRANSPLANTATION; HEART VENTRICLE TACHYCARDIA; HUMAN; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; LEUKOPENIA; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MULTICENTER STUDY; NEUROLOGIC DISEASE; NEW YORK HEART ASSOCIATION CLASS; NONHUMAN; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PERIPHERAL NEUROPATHY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; RASH; TREATMENT DURATION; TRYPANOSOMA CRUZI; AGED; CARDIOVASCULAR DISEASES; CHAGAS CARDIOMYOPATHY; CLINICAL TRIAL; COMPLICATION; DISEASE COURSE; GENETICS; GENOTYPE; ISOLATION AND PURIFICATION; MORTALITY; PARASITE LOAD; PROPORTIONAL HAZARDS MODEL; TREATMENT FAILURE;

ADULT; AGED; CARDIOVASCULAR DISEASES; CHAGAS CARDIOMYOPATHY; CHRONIC DISEASE; DISEASE PROGRESSION; FEMALE; GENOTYPE; HUMANS; MALE; MIDDLE AGED; NITROIMIDAZOLES; PARASITE LOAD; POLYMERASE CHAIN REACTION; PROPORTIONAL HAZARDS MODELS; PROSPECTIVE STUDIES; TREATMENT FAILURE; TRYPANOCIDAL AGENTS; TRYPANOSOMA CRUZI;

EID: 84942265029     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1507574     Document Type: Article

References (40)

1. Chagas disease in Latin America: An epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 2015; 90: 33- 43.
2. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet 2010; 375: 1388- 402.
3. Bern C. Chagas' Disease. N Engl J Med 2015; 373: 456-66.
4. Organización Panamericana de la Salud. Estimación cuantitativa de la enfermedad de Chagas en las Américas. Montevideo, Uruguay: Organización Panamericana de la Salud, 2006: 1-28. (Publication no. OPS/HDM/CD/425-06.).
5. World Health Organization. Annex table 3: burden of disease in DALYs by cause, sex, and mortality stratum in WHO regions, estimates for 2002. World Health Rep 2002 (http://www.who.int/whr/2002/whr2002-annex3.pdf).
6. Rassi A, Rassi A Jr, Rassi GG. Fase aguda. In: Brener Z, Andrade ZA, Barral Neto M. Trypanosoma cruzi e doenoa de Chagas. 2nd ed. Rio de Janeiro: Guanabara Koogan Editora, 2000: 231-45.
7. Marin-Neto JA, Rassi A Jr, Maciel BC, Simoes MV, Schmidt A. Chagas heart disease. In: Yusuf S, Cairns JA, Camm AJ, Fallen EL, Gersh BJ, eds. Evidence-based cardiology. 3rd ed. London: BMJ Books, 2010: 823-41.
8. Rassi A Jr, Rassi A, Little WC, et al. Development and validation of a risk score for predicting death in Chagas' heart disease. N Engl J Med 2006; 355: 799-808.
9. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of chronic Chagas heart disease. Circulation 2007; 115: 1109-23.
10. Marin-Neto JA, Rassi A Jr, Maciel BC. Pathology and pathogenesis of Chagas disease. In: McKenna WJ, Weller PF, Yeon SB, Baron EL, eds. UpToDate in cardiovascular medicine, a CD-ROM textbook. version 5.11. Wellesley, MA: UpToDate in Medicine, 2015.
11. Cunha-Neto E, Coelho V, Guilherme L, Fiorelli A, Stolf N, Kalil J. Autoimmunity in Chagas' disease: identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas' cardiomyopathy patient. J Clin Invest 1996; 98: 1709-12.
12. Iwai LK, Juliano MA, Juliano L, Kalil J, Cunha-Neto E. T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple crossreactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain. J Autoimmun 2005; 24: 111-7.
13. Jones EM, Colley DG, Tostes S, Lopes ER, Vnencak-Jones CL, McCurley TL. A Trypanosoma cruzi DNA sequence amplified from inflammatory lesions in human chagasic cardiomyopathy. Trans Assoc Am Physicians 1992; 105: 182-9.
14. Higuchi MdeL, De Brito T, Martins Reis M, et al. Correlation between Trypanosoma cruzi parasitism and myocardial inflammatory infiltrate in human chronic chagasic myocarditis: light microscopy and immunohistochemical findings. Cardiovasc Pathol 1993; 2: 101-6.
15. Bellotti G, Bocchi EA, de Moraes AV, et al. In vivo detection of Trypanosoma cruzi antigens in hearts of patients with chronic Chagas' heart disease. Am Heart J 1996; 131: 301-7.
16. Andrade SG, Stocker-Guerret S, Pimentel AS, Grimaud JA. Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy. Mem Inst Oswaldo Cruz 1991; 86: 187-200.
17. Garcia S, Ramos CO, Senra JFV, et al. Treatment with benznidazole during the chronic phase of experimental Chagas' disease decreases cardiac alterations. Antimicrob Agents Chemother 2005; 49: 1521-8.
18. Coura JR, de Abreu LL, Willcox HP, Petana W. Comparative controlled study on the use of benznidazole, nifurtimox and placebo, in the chronic form of Chagas' disease, in a field area with interrupted transmission. I. Preliminary evaluation. Rev Soc Bras Med Trop 1997; 30: 139-44. (In Portugese.).
19. Villar JC, Marin-Neto JA, Ebrahim S, Yusuf S. Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection. Cochrane Database Syst Rev 2002; 1: CD003463.
20. Viotti R, Vigliano C, Lococo B, et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: A nonrandomized trial. Ann Intern Med 2006; 144: 724-34.
21. Fabbro DL, Streiger ML, Arias ED, Bizai ML, del Barco M, Amicone NA. Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe City (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution. Rev Soc Bras Med Trop 2007; 40: 1-10.
22. Villar JC, Perez JG, Cortes OL, et al. Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection. Cochrane Database Syst Rev 2014; 5: CD003463.
23. Marin-Neto JA, Rassi A Jr, Morillo CA, et al. Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas' cardiomyopathy: The BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT). Am Heart J 2008; 156: 37-43.
24. Schijman AG, Bisio M, Orellana L, et al. International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients. PLoS Negl Trop Dis 2011; 5(1): e931.
25. Wincker P, Britto C, Pereira JB, Cardoso MA, Oelemann W, Morel CM. Use of a simplified polymerase chain reaction procedure to detect Trypanosoma cruzi in blood samples from chronic chagasic patients in a rural endemic area. Am J Trop Med Hyg 1994; 51: 771-7.
26. Ramírez JD, Guhl F, Rendón LM, Rosas F, Marin-Neto JA, Morillo CA. Chagas cardiomyopathy manifestations and Trypanosoma cruzi genotypes circulating in chronic Chagasic patients. PLoS Negl Trop Dis 2010; 4(11): e899.
27. Zingales B, Miles MA, Campbell DA, et al. The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect Genet Evol 2012; 12: 240-53.
28. Zingales B, Miles MA, Moraes CB, et al. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity. Mem Inst Oswaldo Cruz 2014; 109: 828- 33.
29. Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986; 42: 121-30.
30. de Andrade AL, Zicker F, de Oliveira RM, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet 1996; 348: 1407-13.
31. Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C. Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease. Am J Trop Med Hyg 1998; 59: 526-9.
32. Pérez-Molina JA, Pérez-Ayala A, Moreno S, Fernández-González MC, Zamora J, López-Velez R. Use of benznidazole to treat chronic Chagas' disease: A systematic review with a meta-analysis. J Antimicrob Chemother 2009; 64: 1139-47.
33. Kuschnir E, Sgammini H, Castro R, Evequoz C, Ledesma R, Brunetto J. Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy. Arq Bras Cardiol 1985; 45: 249-56. (In Spanish.).
34. Molina I, Gómez i Prat J, Salvador F, et al. Randomized trial of posaconazole and benznidazole for chronic Chagas' disease. N Engl J Med 2014; 370: 1899-908.
35. Carmo AA, Rocha MO, Silva JL, et al. Amiodarone and Trypanosoma cruzi parasitemia in patients with Chagas disease. Int J Cardiol 2015; 189: 182-4.
36. Veloso VM, Carneiro CM, Toledo MJO, et al. Variation in susceptibility to benznidazole in isolates derived from Trypanosoma cruzi parental strains. Mem Inst Oswaldo Cruz 2001; 96: 1005-11.
37. Bern C, Montgomery SP, Herwaldt BL, et al. Evaluation and treatment of chagas disease in the United States: A systematic review. JAMA 2007; 298: 2171-81.
38. Andrade JP, Marin Neto JA, Paola AA, et al. I Latin American guidelines for the diagnosis and treatment of Chagas' heart disease: executive summary. Arq Bras Cardiol 2011; 96: 434-42.
39. Fabbro DL, Danesi E, Olivera V, et al. Trypanocide treatment of women infected with Trypanosoma cruzi and its effect on preventing congenital Chagas. PLoS Negl Trop Dis 2014; 8(11): e3312.
40. Tarleton RL, Gürtler RE, Urbina JA, Ramsey J, Viotti R. Chagas disease and the London declaration on neglected tropical diseases. PLoS Negl Trop Dis 2014; 8(10): e3219.