Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Clinical Trial

NCT02386358 | Completed Phase 3 DMC

• 1 other identifier: TRAENA
• Study Type: interventional
• Target: 910
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is:

1. 1.-to determine whether benznidazole (BZN) will be able to modify the natural evolution of chronic Chagas disease in adult patients by means of a randomized, double-blind clinical trial (RCT).
2. 2.-to validate therapeutic efficacy with new methods, such as recombinant antigen F29 of Trypanosoma cruzi visualized by conventional ELISA, in the context of the RCT compared with conventional serology (CS)
3. 3.-to develop the real-time polymerase chain-reaction (RT-PCR) to quantify the parasite load as an early therapeutic effect.
4. 4.to determine the potential of such serological and parasitological methods as predictors of therapeutic effect or failure.

Conditions

Chagas Disease

Keywords

Chronic Chagas Disease; Randomized Clinical Trial double blind; Benznidazole vs Placebo; Adult patients

Outcome Measures

Primary Outcomes (3)

• Cardiovascular Mortality

  Sudden death, unexpectedly in time and in its presentation,preceded by the abrupt loss of consciousness within a maximum of one hour of the onset of symptoms,when it happened during sleep or unexpectedly in a patient was stable until then. Related Death, when presented in a patient with signs of progressive heart failure.Ischemic or Hemorrhagic Stroke

  Time to event: from date of randomization until the date of first documented progression or date of death from any cause up to 10 years of follow-up

• Development of heart failure

  Dyspnea is evaluated according to the classification of the New York Heart Association (NYHA),gallop rhythm, jugular venous distension, crackles in the lungs, edema or pleural effusion,hepatomegaly

  Time to event: from date of randomization until the date of first documented progression of heart failure up to 10 years of follow-up

• Severe arrhythmias with hemodynamic compromise or pacemaker implant or Implantable cardiac defibrillator

  Sustained ventricular tachycardia, atrioventricular block, trifascicular block, Atrial fibrillation

  Time to event: from date of randomization until the date of first documented progression up to 10 years of follow-up

Secondary Outcomes (9)

• Electrocardiographic endpoints. New development of permanent changes in the electrocardiographic

  Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up

• Changes in clinical stage in chronic Chagas disease

  Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up

• Enlargement of the left ventricle (LV) detected by echocardiography.

  Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up

• New Heart Failure

  Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up

• Stroke

  Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up

Study Arms (2)

Benznidazole

ACTIVE COMPARATOR

Benznidazole pills of 100 mg, dose 5 mg/Kg/day, twice a day during 60 days

Drug: Benznidazole

Placebo

PLACEBO COMPARATOR

Placebo pills 100 mg, dose 5mg/Kg/day, twice a day, during 60 days

Drug: Placebo

Interventions

Benznidazole DRUG

Benznidazole at a dose 5 mg/Kg/day until 60 days have been completed or development of non-acceptable toxicity-

Also known as: Radanil (Roche Laboratory)

Benznidazole

Placebo DRUG

Placebo at a dose 5 m/Kg/day until 60 days

Also known as: Placebo pills

Placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients living in urban areas
• Reactive to at least 2 for serological test performed in Fatala Chaben Institute (ELISA and IFI) ,
• Patients who agreed to be part of this protocol through informed consent form signed

You may not qualify if:

• Patients with chronic Chagas disease who have received prior treatment with benznidazole
• Other cardiomyopathies : idiopathic , alcoholic , peripartum myocarditis, secondary to coronary artery disease, valve disease, hypertension, restrictive, hypertrophic or congenital
• Chronic renal disease
• Bleeding disorders
• History of liver disease or current liver disease ,
• Any other severe clinical disease that decreases their life expectancy
• History of severe allergies
• Pregnant patients
• Patients who have not signed the informed consent.

Sponsors & Collaborators

• Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben: lead
• National Council of Scientific and Technical Research, Argentina: collaborator
• Pan American Health Organization: collaborator
• Becas Carrillo Oñativia, Ministerio de Salud, Argentina: collaborator
• Drugs for Neglected Diseases: collaborator

Study Sites (1)

Instituto Nacional de Parasitología Dr Mario Fatala Chaben

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1063, Argentina

Location

Related Publications (9)

• 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 Oct;59(4):526-9. doi: 10.4269/ajtmh.1998.59.526.

  PMID: 9790423 RESULT

• de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, Almeida IC, de Andrade SS, de Andrade JG, Martelli CM. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet. 1996 Nov 23;348(9039):1407-13. doi: 10.1016/s0140-6736(96)04128-1.

  PMID: 8937280 RESULT

• Viotti R, Vigliano C, Armenti H, Segura E. Treatment of chronic Chagas' disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J. 1994 Jan;127(1):151-62. doi: 10.1016/0002-8703(94)90521-5.

  PMID: 8273735 RESULT

• Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti A. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med. 2006 May 16;144(10):724-34. doi: 10.7326/0003-4819-144-10-200605160-00006.

  PMID: 16702588 RESULT

• Porcel BM, Bontempi EJ, Henriksson J, Rydaker M, Aslund L, Segura EL, Pettersson U, Ruiz AM. Trypanosoma rangeli and Trypanosoma cruzi: molecular characterization of genes encoding putative calcium-binding proteins, highly conserved in trypanosomatids. Exp Parasitol. 1996 Dec;84(3):387-99. doi: 10.1006/expr.1996.0127.

  PMID: 8948328 RESULT

• 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 Oct;45(4):249-56. No abstract available. Spanish.

  PMID: 3835868 RESULT

• Reyes PA, Vallejo M. Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection). Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004102. doi: 10.1002/14651858.CD004102.pub2.

  PMID: 16235350 RESULT

• Villar JC, Perez JG, Cortes OL, Riarte A, Pepper M, Marin-Neto JA, Guyatt GH. Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection. Cochrane Database Syst Rev. 2014 May 27;2014(5):CD003463. doi: 10.1002/14651858.CD003463.pub2.

  PMID: 24867876 RESULT

• Schijman AG, Bisio M, Orellana L, Sued M, Duffy T, Mejia Jaramillo AM, Cura C, Auter F, Veron V, Qvarnstrom Y, Deborggraeve S, Hijar G, Zulantay I, Lucero RH, Velazquez E, Tellez T, Sanchez Leon Z, Galvao L, Nolder D, Monje Rumi M, Levi JE, Ramirez JD, Zorrilla P, Flores M, Jercic MI, Crisante G, Anez N, De Castro AM, Gonzalez CI, Acosta Viana K, Yachelini P, Torrico F, Robello C, Diosque P, Triana Chavez O, Aznar C, Russomando G, Buscher P, Assal A, Guhl F, Sosa Estani S, DaSilva A, Britto C, Luquetti A, Ladzins J. International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients. PLoS Negl Trop Dis. 2011 Jan 11;5(1):e931. doi: 10.1371/journal.pntd.0000931.

  PMID: 21264349 RESULT

Related Links

• National Administration of Health Laboratories and Institutes "Dr Carlos G. Malbrán"/ National Institute of Parasitology

MeSH Terms

Conditions

Chagas Disease

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• Adellina R Riarte, MD

  Chief of Clinical, Pathology and Treatment Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adelina Rosa Riarte MD

Study Record Dates

• First Submitted: January 19, 2015
• First Posted: March 11, 2015
• Study Start: March 1, 1999
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: March 11, 2015

Record last verified: 2015-03

Locations

AR (1)