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

Sponsor

Universidad Autónoma de Bucaramanga (Other)

Overall Status

Unknown status

CT.gov ID

NCT02369978

Collaborator

Fundación Cardioinfantil Instituto de Cardiología (Other), Instituto Nacional de Salud, Colombia (Other), Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben (Other)

500

Enrollment

Location

Arms

42.1

Anticipated Duration (Months)

11.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chagas Disease	Drug: Nifurtimox Drug: Benznidazole Drug: Placebo	Phase 2/Phase 3

Detailed Description

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

To evaluate the feasibility of conducting a multinational trial in terms of
the ability to identify and recruit T. cruzi-infected individuals without clinical disease in a relatively short period
the standardization of procedures to test the parasitic load using polymerase chain reaction (PCR)
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.
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.
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.
To evaluate the equivalence of the treatment schedules with NFX as compared with those with BZN 5
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
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).
To explore, among individuals treated with placebo, the level of agreement in the tests of parasitic load at baseline and during the follow up.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 1, 2015

Anticipated Primary Completion Date :

Aug 1, 2018

Anticipated Study Completion Date :

Feb 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nifurtimox (NFX) 60 days of active treatment with full-dose, or 120 days of active treatment with half-dose (allocation ratio 1:1). The 60-day group will receive active treatment in the first or second half of a 120-day treatment window, as per random allocation. The active treatment period will be followed/preceded by matching placebo (see placebo arm below)	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 Other Names: Lampit (Bayer)
Active Comparator: Benznidazole (BZN) 60 days of active treatment with full-dose, or 120 days of active treatment with half-dose (allocation ratio 1:1). The 60-day group will receive active treatment in the first or second half of a 120-day treatment window, as per random allocation. The active treatment period will be followed/preceded by matching placebo (see placebo arm below)	Drug: 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 Other Names: Radanil (Roche), Rochagan (Roche), Abarax (ELEA)
Placebo Comparator: Placebo 120 days of treatment with matching placebo	Drug: Placebo Two capsules of matching placebo (contaning Magnesium stearate and cellulose) B.I.D Other Names: Control group

Arm

Intervention/Treatment

Experimental: Nifurtimox (NFX)

60 days of active treatment with full-dose, or 120 days of active treatment with half-dose (allocation ratio 1:1). The 60-day group will receive active treatment in the first or second half of a 120-day treatment window, as per random allocation. The active treatment period will be followed/preceded by matching placebo (see placebo arm below)

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

Other Names:

Lampit (Bayer)

Active Comparator: Benznidazole (BZN)

Drug: 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

Other Names:

Radanil (Roche), Rochagan (Roche), Abarax (ELEA)

Placebo Comparator: Placebo

120 days of treatment with matching placebo

Drug: Placebo

Two capsules of matching placebo (contaning Magnesium stearate and cellulose) B.I.D

Other Names:

Control group

Outcome Measures

Primary Outcome Measures

Quantitative Polymerase Chain Reaction (qPCR) for Trypanosoma cruzi [12 - 18 months after starting therapy]
Proportion of participants with at least one out of three positive tests (performed at least one week apart from each other)

Secondary Outcome Measures

T. cruzi positive serology status [12 months after starting therapy]
Proportion of participants with positive T. cruyzi serology status
Mean change in T. cruzi antibody titers [12 months after starting therapy]
Mean change (before-after) in antibody readings as measured with ELISA serology

Other Outcome Measures

Reported adverse reactions [60 days after starting therapy]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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