Clinical trial NCT02369978: CHICAMOCHA 3 - Equivalence of Usual Interventions for Trypanosomiasis (EQUITY)
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Chagas Disease
Keywords: Trypanocidal therapy
Benznidazole
Nifurtimox
Polymerase chain reaction
Randomized trial
Lead sponsor: Universidad Autónoma de Bucaramanga
Sponsor class: OTHER
Collaborators: name: Fundación Cardioinfantil Instituto de Cardiología
name: Instituto Nacional de Salud, Colombia
name: Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben
First posted: 2015-02-24
Enrollment: 500
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Quantitative Polymerase Chain Reaction (qPCR) for Trypanosoma cruzi
timeFrame: 12 - 18 months after starting therapy
Secondary outcomes:
measure: T. cruzi positive serology status
timeFrame: 12 months after starting therapy
measure: Mean change in T. cruzi antibody titers
timeFrame: 12 months after starting therapy
Other outcomes:
measure: Reported adverse reactions
timeFrame: 60 days after starting therapy
Locations:
city: Bucaramanga
country: Colombia
facility: Fundación Oftalmológica de Santander - Clínica Ardila Lulle (FOSCAL)
state: Santander
Study officials:
affiliation: Universidad Autónoma de Bucaramanga
name: Juan C Villar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Villar JC, Herrera VM, Perez Carreno JG, Vaquiro Herrera E, Castellanos Dominguez YZ, Vasquez SM, Cucunuba ZM, Prado NG, Hernandez Y. Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis - EQUITY): study protocol for a randomised controlled trial. Trials. 2019 Jul 15;20(1):431. doi: 10.1186/s13063-019-3423-3.