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

NCT ID: NCT02369978

Last Updated: 2017-07-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2019-02-28

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.

Conditions

Chagas Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

Nifurtimox

Intervention Type: DRUG

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 (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)

Group Type: ACTIVE_COMPARATOR

Benznidazole

Intervention Type: DRUG

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

120 days of treatment with matching placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Lampit (Bayer); Radanil (Roche), Rochagan (Roche), Abarax (ELEA); Control group

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación Cardioinfantil Instituto de Cardiología

OTHER

Sponsor Role: collaborator

Instituto Nacional de Salud, Colombia

OTHER_GOV

Sponsor Role: collaborator

Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben

OTHER_GOV

Sponsor Role: collaborator

Universidad Autónoma de Bucaramanga

OTHER

Sponsor Role: lead

Responsible Party

Juan Carlos Villar, MD, PhD

Professor, Department of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan C Villar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Autónoma de Bucaramanga

Locations

Fundación Oftalmológica de Santander - Clínica Ardila Lulle (FOSCAL)

Bucaramanga, Santander Department, Colombia

Site Status: RECRUITING

Countries

Colombia

Central Contacts

Juan C Villar, MD, PhD

Role: CONTACT

jvillar@unab.edu.co

+5776436111 ext. 514

Bernardo I Useche, PhD

Role: CONTACT

buseche@unab.edu.co

+5776436111 ext. 539

Facility Contacts

Gustavo A Parra, MD

Role: primary

guparra@unab.edu.co

Skarlet M Vásquez, RN, MSc

Role: backup

svasquez196@unab.edu.co

References

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.

Reference Type: BACKGROUND

PMID: 24867876 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31307503 (View on PubMed)

Other Identifiers

124156935014

Identifier Type: -

Identifier Source: org_study_id