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

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)

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.

Study Overview

• Status: Unknown
• Conditions: Chagas Disease
• Intervention / Treatment: Drug: Nifurtimox; Drug: Benznidazole; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Juan C Villar, MD, PhD; Phone Number: 514 +5776436111; Email: jvillar@unab.edu.co
• Study Contact Backup: Name: Bernardo I Useche, PhD; Phone Number: 539 +5776436111; Email: buseche@unab.edu.co

Study Locations

• Colombia
  • Santander
    • Bucaramanga, Santander, Colombia
      • Recruiting
      • Fundación Oftalmológica de Santander - Clínica Ardila Lulle (FOSCAL)
      • Contact: Gustavo A Parra, MD; Email: guparra@unab.edu.co
      • Contact: Skarlet M Vásquez, RN, MSc; Email: svasquez196@unab.edu.co

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant 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); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Universidad Autónoma de Bucaramanga
• Collaborators: Fundación Cardioinfantil Instituto de Cardiología; Instituto Nacional de Salud, Colombia; Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben
• Investigators: Principal Investigator: Juan C Villar, MD, PhD, Universidad Autonoma de Bucaramanga

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: Trials. 2019 Aug 20;20(1):516.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): February 1, 2019

Study Registration Dates

• First Submitted: February 17, 2015
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimate): February 24, 2015

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Randomized trial; Polymerase chain reaction; Benznidazole; Nifurtimox; Trypanocidal therapy
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Euglenozoa Infections; Trypanosomiasis; Chagas Disease; Physiological Effects of Drugs; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents; Nifurtimox; Benzonidazole
• Other Study ID Numbers: 124156935014