BENEFIT: Evaluation of the Use of Antiparasital Drug (Benznidazole) in the Treatment of Chronic Chagas' Disease

• Sponsor: Population Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00123916
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other), World Health Organization (Other), Instituto Dante Pazzanese de Cardiologia (Other), University of Sao Paulo (Other)
• Enrollment: 2,854
• Locations: 47
• Arms: 2
• Duration (Months): 129
• Patients Per Site: 60.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC).

The BENEFIT study is being conducted by the Population Health Research Institute (in Hamilton, Canada) and the Institute Dante Pazzanese de Cardiologia (Sao Paulo, Brazil) together with a Steering Committee, and an independent Safety Monitoring Board.

Condition or Disease	Intervention/Treatment	Phase
Chagas Disease; Trypanosomiasis; Heart Disease	Drug: Benznidazole; Drug: Placebo	Phase 3

Detailed Description

A randomized double-blind controlled clinical trial investigating the role of benznidazole in patients with chronic Chagas' heart disease.

Chagas disease has 3 phases: acute, undetermined and chronic phases. There are no clinical trials up to date that have investigated the use of antiparasitic drugs in patients that are in the chronic phase.

This study will evaluate the efficacy and safety of benznidazole (an antiparasitic drug) in patients with chronic Chagas' heart disease. Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC). It will be developed in 49 study centres in Argentina, Bolivia,Brazil,Colombia, and El Salvador - countries with high incidence of Chagas Disease.

The Pilot study is evaluating if benznidazole is effective in producing parasitic cure (PCR negativization or reducing parasitic load) in chronic Chagas Disease as well as assessing the feasibility of conducting a large trial in chronic Chagas Disease in South America.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2854 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Benznidazole Evaluation for Interrupting Trypanosomiasis - The BENEFIT Trial
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Benznidazole 40 - 80 days (according to body weight) treatment with benznidazol	Drug: Benznidazole; Daily po Benznidazole or placebo (weight based) during 40 - 80 days (depending on body weight); Other Names: Rochagan/LaFepe
Placebo Comparator: Placebo 40 - 80 days (according to body weight) treatment with matching placebo	Drug: Placebo; a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 - 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg); Other Names: Rochagan/LaFepe

Outcome Measures

Primary Outcome Measures

1. Composite of First of cardiovascular events: Death, Resuscitated Cardiac Arrest, Sustained VentricularTachycardia, New/worsening Heart Failure, New Pacemaker/ICD, Stroke/TIA or other Embolic Events, Cardiac Transplant. [through study completion, an average of 5 years]

   Composite cardiovascular outcome,

Secondary Outcome Measures

1. New development of any of the following echo changes, segmental wall motion abnormalities, ventricular aneurysm, reduction in LV ejection fraction >5%, increase in LVDD> 5 mm compared to baseline. [through study completion, an average of 5 years]

2. New 12 lead ECG alterations (complete bundle branch block, fascicular block, advanced atrio-ventricular block, atrial fibrillation, etc). [through study completion, an average of 5 years]

3. Progression of NYHA functional class by at least one category [through study completion, an average of 5 years]

4. New 12 lead electrocardiogram (ECG) alterations (complete bundle branch block; fascicular block, advanced atrio-ventricular block, atrial fibrillation, etc.) [through study completion, an average of 5 years]

5. Progression of New York Heart Association (NYHA) functional class by at least one category [through study completion, an average of 5 years]

6. Evaluation of safety (adverse events: dermatitis, peripheral neuropathy, gastro-intestinal intolerance, leucopenia [2500 x 10^9 L]), tolerance and adherence to treatment [through study completion, an average of 5 years]

7. Determination of the efficacy of benznidazole in patients with Chronic Chagas heart disease based on a 50% reduction in both qualitative and quantitative PCR. [through study completion, an average of 5 years]

   Polymerase Chain Reaction study on patient's blood samples and report negativization at the end of treatment, 2Y and final visit.

8. Safety and tolerability of benznidazole [through study completion, an average of 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Consenting patients (between 18 and 75 years of age) with serological evidence of Chagas infection (any combination of 2 positive tests) and that have one or more of the following:

• Abnormal electrocardiogram with at least two components (complete RBBB or LBBB; left anterior or posterior fascicular block; ventricular premature beat; first degree atrioventricular [AV] block; Mobitz type I AV block; sinus bradycardia; primary ST-T changes; abnormal Q waves; low voltage QRS; or atrial fibrillation);

• Abnormal ECG (Mobitz type II, advanced or third degree AV block);

• Increased cardiothoracic ratio (> 0.50);

• Complex ventricular arrythmias on 24 hour ambulatory ECG monitoring;

• Evidence of regional wall motion abnormality or reduced global left ventricular systolic function or increased left ventricular and diastolic diameter on 2D-Echo.

Exclusion Criteria:

Patients will be excluded if having:

• NYHA heart failure class IV or decompensated heart failure

• Evidence of concomitant coronary artery disease (CAD) or other etiology of dilated cardiomyopathy

• Previous treatment with antitrypanosomal agents or an accepted indication for antiparasitic therapy

• Inability to comply with follow-up visits

• History of severe alcohol abuse within 2 years

• Known chronic renal or hepatic insufficiency or hepatic insufficiency

• Pregnancy or breast feeding

• Megaesophagus with swallowing impairment

• Other severe disease significantly curtailing life expectancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BENEFIT Ivestigational Site	Ciudad Autónoma de Buenos Aires	Apital Federal	Argentina	3556
2	BENEFIT Investigational Site	Belén De Escobar	Buenos Aires	Argentina	1753
3	BENEFIT Investigational Site	Isidro Casanova	Buenos Aires	Argentina	1282
4	BENEFIT Investigational Site	San Juan	Buenos Aires	Argentina	1625
5	BENEFIT Investigational Site	Santiago del Estero	Buenos Aires	Argentina	4200
6	BENEFIT Investigational Site	Santiago del Estero	Buenos Aires	Argentina	5400
7	BENEFIT Investigational Site	Ciudad Autónoma de Buenos Aires	Capital Federal	Argentina	1063
8	BENEFIT Investigational Site	San Fernando del Valle de Catamarca	Catamarca	Argentina
9	BENEFIT Investigational Site	Charata	Chaco	Argentina	H3730AVI
10	BENEFIT Investigational Site	Paraná	Entre Rios	Argentina	3100
11	BENEFIT Investigational Site	Buenos Aires	General Rodríguez Partido	Argentina
12	BENEFIT Investigational Site	San Salvador de Jujuy	Jujuy	Argentina	4600
13	BENEFIT Investigational Site	Corrientes	Rosario, Santa Fe	Argentina	3400
14	BENEFIT Investigational Site	Rosario	Santa Fe	Argentina	2000
15	BENEFIT Investigational Site	Añatuya	Santiago Del Estero	Argentina	3760
16	BENEFIT Investigational Site	Santiago Del Estero	Sgo. Del Estero	Argentina	4200
17	BENEFIT Investigational Site	Buenos Aires		Argentina
18	BENEFIT Investigational Site	Salta		Argentina	A4406CLA
19	BENEFIT Investigational Site	Tupiza	Potosi	Bolivia
20	BENEFIT Investigational Site	Salvador	Bahaia	Brazil	40050-410
21	BENEFIT Investigational Site	Salvador	Bahaia	Brazil	40110-909
22	BENEFIT Investigational Site	Salvador	Bahaia	Brazil	40425-060
23	BENEFIT Investigational Site	Carmo	Belo Horizonte	Brazil	30130-690
24	BENEFIT Investigational Site	Brasília	Brazilian Federal District	Brazil	70658-700
25	BENEFIT Investigational Site	Goiânia	GO	Brazil	74110-010
26	BENEFIT Investigational Site	Goiânia	GO	Brazil	74110-020
27	BENEFIT Investigational Site	Goiânia	GO	Brazil	74605-050
28	BENEFIT Investigational Site	Uberlandia	MG	Brazil	38025-440
29	BENEFIT Investigational Site	Uberlândia	MG	Brazil	38400-299
30	BENEFIT Investigational Site	Uberaba	Minas Gerais	Brazil	38010-160
31	BENEFIT Investigational Site	Curitiba	Parana	Brazil	80060-900
32	BENEFIT Investigational Site	Recife	Pernambuco	Brazil	50100-130
33	BENEFIT Investigational Site	Pelotas	Rio Grande Do Sul	Brazil	96015-290
34	BENEFIT Investigational Site	Campinas	São Paulo	Brazil	13059-740
35	BENEFIT Investigational Site	Ribeirão Preto	São Paulo	Brazil	14048-900
36	BENEFIT Investigational Site	São José do Rio Preto	São Paulo	Brazil	15015-210
37	BENEFIT Investigational Site	São José do Rio Preto	São Paulo	Brazil	15090-000
38	BENEFIT Investigational Site	Votuporanga	São Paulo	Brazil	15500-003
39	BENEFIT Investigational Site	Rio de Janeiro		Brazil	21040-360
40	BENEFIT Investigational Site	Rio de Janeiro		Brazil	21941-913
41	BENEFIT Investigational Site	São Paulo		Brazil	01417 010
42	BENEFIT Investigational Site	São Paulo		Brazil	04012-909
43	BENEFIT Investigational Site	São Paulo		Brazil	05403-000
44	BENEFIT Investigational Site	São Paulo		Brazil	05403-901
45	BENEFIT Investigational Site	Bogota	Bogotá	Colombia
46	BENEFIT Investigational Site	San Gil	Santander	Colombia
47	BENEFIT Ivestigational Site	San Salvador		El Salvador

Sponsors and Collaborators

• Population Health Research Institute
• Canadian Institutes of Health Research (CIHR)
• World Health Organization
• Instituto Dante Pazzanese de Cardiologia
• University of Sao Paulo

Investigators

• Study Chair: Carlos Morillo, MD, Population Health Research Institute - McMaster University
• Study Chair: Jose Antonio Marin-Neto, MD, PhD, University of Sao Paulo
• Study Chair: Salim Yusuf, MD, DPh, Population Health Research Institute - McMaster University
• Principal Investigator: Sergio Sosa-Estani, MD, PhD, Argentina National Coordinator - CenDIE, Argentina
• Principal Investigator: Fernando Rosas, M.D., Fundacion Clinica Shaio, Bogota, Colombia

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Population Health Research Institute

Publications

• Marin-Neto JA, Rassi A Jr, Morillo CA, Avezum A, Connolly SJ, Sosa-Estani S, Rosas F, Yusuf S; BENEFIT Investigators. 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 Jul;156(1):37-43. doi: 10.1016/j.ahj.2008.04.001.

• Responsible Party: Salim Yusuf's office, Principal Co-Investigator, Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT00123916
• Other Study ID Numbers: BEN01; CONEP-11394
• First Posted: Jul 26, 2005
• Last Update Posted: Mar 3, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Salim Yusuf's office, Principal Co-Investigator, Population Health Research Institute: Chagas Disease; Trypanosomiasis; Benznidazole; Chronic Heart disease; Trypanosoma Cruzi
• Additional relevant MeSH terms: Chagas Disease; Trypanosomiasis; Heart Diseases; Benzonidazole

Study Results

No Results Posted as of Mar 3, 2020