CHICAMOCHA 3 - Equivalence of Usual Interventions for Trypanosomiasis (EQUITY)

Chagas Disease Clinical Trial

— CHICAMOCHA-3  

Official title:

Cardiovascular Health Investigation and Collaboration From Countries of America to Assess the Markers and Outcomes of Chagas Disease (CHICAMOCHA-3) - EQUITY (Equivalence of Usual Interventions for Trypanosomiasis)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02369978
• Other study ID #: 124156935014
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: February 17, 2015
• Last updated: July 18, 2017
• Start date: August 2015
• Est. completion date: February 2019

Study information

• Verified date: July 2017
• Source: Universidad Autónoma de Bucaramanga
• Contact: Juan C Villar, MD, PhD
• Phone: +5776436111
• Email: jvillar[@]unab.edu.co
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, blind, parallel-group trial will evaluate the efficacy and safety of Nifurtimox (NFX) and Benznidazole (BZN), the two usual interventions to treat the parasite Trypanosoma cruzi.

The investigators will test whether NFX is an effective trypanocidal agent (by comparison with placebo) and equivalent to BZN (as active comparator) in terms of both parasite-related and safety outcomes.

Individuals found seropositive and without clinical signs of dilated cardiomyopathy will receive either of the active treatments or matching placebo. Participants allocated to NFX or BZN will receive either a 60-day (full-dose) or a 120-day (half-dose) active treatment, whereas the control group will receive placebo for 120 days. There will be thus four arms of active treatment (NFX60, NFX120, BZN60 and BZN120), and a fifth control arm receiving placebo (1:1:1:1:1 allocation ratio) where every participant in the trial will take 120 days of study drug (the groups receiving full-dose will complete a 120-day masked treatment with placebo).

The study plans to enroll 500 participants from Colombia (in two different geographical areas) and Argentina, in order to explore regional differences in the treatment effects.

Description:

The specific aims of this multi-center randomized trial include:

1. To evaluate the feasibility of conducting a multinational trial in terms of

1. the ability to identify and recruit T. cruzi-infected individuals without clinical disease in a relatively short period

2. the standardization of procedures to test the parasitic load using polymerase chain reaction (PCR)

2. To evaluate, in the study population, the efficacy of a treatment with NFX using conventional (full) dose (8/mg/Kg/day) or half-dose for a variable duration (full-dose for 60 days versus half-dose for 120 days) in terms of the presence of positive PCR tests one year after treatment, as compared with placebo.

3. To evaluate the equivalence (in terms of non-inferiority of its impact over the PCR testing) of two treatment schedules with NFX: a full-dose treatment for 60 days and a half-dose treatment for 120 days.

4. To evaluate the equivalence of two treatment schedules with BZN: A conventional (full) dose of 5 mg/Kg/day) for 60 days, as compared with half-dose treatment for 120 days.

5. To evaluate the equivalence of the treatment schedules with NFX as compared with those with BZN 5

6. To evaluate the safety (in terms of reporting of mild symptoms, limitation of daily activities or hospitalizations, biochemical or blood abnormalities commonly reported by individuals taking these treatments) and adherence to the allocated treatments among individuals receiving NFX or BZN for varying duration and dose, as compared with placebo

7. To explore differences in the impact of active treatments on the PCR among four subgroups of interest (geographical origin, T. cruzi discrete type unit found, parasitic load at baseline and age of participants).

8. To explore, among individuals treated with placebo, the level of agreement in the tests of parasitic load at baseline and during the follow up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: February 2019
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

Inclusion Criteria:

• Positive serology status to Trypanosoma cruzi

• No clinical signs of dilated cardiomyopathy

Exclusion Criteria:

• Unacceptable risk of re-infection, based on the investigators judgment

• Previous treatment with NFX or BZN

• History of peripheral neuropathy

• Health condition limiting the mobility, cognitive function or life expectancy within two years of the enrollment visit

• Pregnancy / Unwilling to use reliable contraceptive methods during childbearing age

Related Conditions & MeSH terms

• Chagas Disease
• Trypanosomiasis

Intervention

Drug:
• Nifurtimox
Full dose: 8 mg/Kg/day, assuming an average weight of 60 Kg: 240 mg B.I.D Half-dose: 120 mg B.I.D
• Benznidazole
Full dose: 5 mg/Kg/day, assuming an average weight of 60 Kg: 150 mg B.I.D Half dose: 75 mg B.I.D
• Placebo
Two capsules of matching placebo (contaning Magnesium stearate and cellulose) B.I.D

Locations

Country	Name	City	State
Colombia	Fundación Oftalmológica de Santander - Clínica Ardila Lulle (FOSCAL)	Bucaramanga	Santander

Sponsors (4)

Lead Sponsor	Collaborator
Universidad Autónoma de Bucaramanga	Fundación Cardioinfantil Instituto de Cardiología, Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben, Instituto Nacional de Salud (Colombia)

Country where clinical trial is conducted

Colombia, 

References & Publications (1)

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;(5):CD003463. doi: 10.1002/14651858.CD003463.pub2. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Reported adverse reactions	Proportion of participants with at least one of the following a) Reporting hospitalization or inability to work b) Stopping study treatment because of adverse reactions /intolerance c) having abnormal levels of at least two biochemical or blood markers	60 days after starting therapy
Primary	Quantitative Polymerase Chain Reaction (qPCR) for Trypanosoma cruzi	Proportion of participants with at least one out of three positive tests (performed at least one week apart from each other)	12 - 18 months after starting therapy
Secondary	T. cruzi positive serology status	Proportion of participants with positive T. cruyzi serology status	12 months after starting therapy
Secondary	Mean change in T. cruzi antibody titers	Mean change (before-after) in antibody readings as measured with ELISA serology	12 months after starting therapy