A Study to Learn How Well Nifurtimox Works and How Safe it is in Children Aged 0 to 17 Years With Chagas' Disease, an Inflammatory, Infectious Disease Caused by the Parasite Trypanosoma Cruzi

NCT ID: NCT02625974

Last Updated: 2024-08-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

330 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-27

Study Completion Date

2021-08-10

Brief Summary

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Researchers are looking for a better way to treat children who have an infectious disease caused by the parasite Trypanosoma cruzi (Chagas' disease).

Chagas'disease is an inflammatory, infectious disease caused by the parasite Trypanosoma cruzi. This parasite is mainly spread by insects called triatomine bug. If Chagas' disease is left untreated, it can later cause serious heart and digestive problems.

The study treatment nifurtimox has been used for more than 50 years to treat Chagas' disease. When used early after infection, it kills the parasite. In people who have long-term Chagas' disease, it's no longer possible to kill the parasite. However, nifurtimox may help slow the progression of the disease and its most serious complications.

Nifurtimox was developed for use in adults only, but has also been used in children (off-label) for over 40 years. Currently it is available for doctors to give to adults and to children. However, there are not enough data about nifurtimox in children.

The main purpose of this study is to learn how well nifurtimox works in children aged 8 months to less than 18 years with Chagas' disease. To answer this, the researchers will compare the amount of antibodies against the parasite Trypanosoma cruzi in the serum (fluid from blood without the clotting factors) between children treated with nifurtimox for 60 days with untreated children from the past (control group):

* 12 months and
* 4 years after the end of treatment. The data for the control group will come from 2 previous studies conducted in children.

Detailed Description

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Conditions

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Chagas Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Nifurtimox 60 days / Arm 1

Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)

Group Type EXPERIMENTAL

Nifurtimox (Lampit, BAYA2502)

Intervention Type DRUG

For pediatric participants with body weight ≤ 40 kg: dosage 10 to 20 mg/kg/day in three divided doses.

For pediatric participants with body weight \> 40 kg: 8 - 10 mg/kg/day in three divided doses.

60 days or 30 days of nifurtimox treatment

Nifurtimox 30 days / Arm 2

Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)

Group Type EXPERIMENTAL

Nifurtimox (Lampit, BAYA2502)

Intervention Type DRUG

For pediatric participants with body weight ≤ 40 kg: dosage 10 to 20 mg/kg/day in three divided doses.

For pediatric participants with body weight \> 40 kg: 8 - 10 mg/kg/day in three divided doses.

60 days or 30 days of nifurtimox treatment

Placebo

Intervention Type DRUG

Matching placebo

Interventions

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Nifurtimox (Lampit, BAYA2502)

For pediatric participants with body weight ≤ 40 kg: dosage 10 to 20 mg/kg/day in three divided doses.

For pediatric participants with body weight \> 40 kg: 8 - 10 mg/kg/day in three divided doses.

60 days or 30 days of nifurtimox treatment

Intervention Type DRUG

Placebo

Matching placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Part 1:

* Male and female pediatric subjects aged 0 days to younger than 18 years
* Chagas' disease diagnosed/ confirmed for a) Subjects \< 8 months of age at randomization must demonstrate direct observation of Trypanosoma cruzi by concentration test; b) Subjects ≥ 8 months to \< 18 years of age at randomization must demonstrate a positive conventional ELISA result for both recombinant ELISA and total purified antigen ELISA

Part 2:

\- Male and female subjects who were randomized and received at least one dose of their assigned 60- or 30-day regimen of nifurtimox treatment

Exclusion Criteria

Part 1:

* Subjects aged 0 to 27 days who, at birth, were pre-term, weighed less than 2500 g, or had a maximum Apgar score \< 7 at 5 minutes
* Known evidence of Chagas' disease-related cardiomyopathy/ Chagas' heart disease
* Known evidence of Chagas' disease-related gastrointestinal dysfunction (e.g. megaoesophagus, megacolon, or both) or Chagas' digestive disease
* Serious manifestations of acute Chagas' disease, including myocarditis, meningoencephalitis, or pneumonitis
* Known evidence of Chagas' disease-related damage to the peripheral nervous system or peripheral neuropathy
* Clinically significant psychiatric disorder (e.g. moderate to severe depression, severe anxiety, or psychosis) or epilepsy
* Subjects with contraindications/ warnings to nifurtimox administration, or with conditions that may increase the risk of the undesirable effects of nifurtimox
* Subjects who have had previous treatment with trypanocidal agents or an accepted indication for antiparasitic therapy (e.g. reactivation of Chagas' infection due to immunosuppression by several diseases or treatment with steroids)
* Subjects living in housing conditions where there is no active or effective vector control to Trypanosoma cruzi reinfection as determined by Ministry of Health guidelines in each country

Part 2:

* Subjects with acute or chronic health conditions or congenital disorders which, in the opinion of the investigator, would make them unsuitable for participation in the clinical study
* Subjects living in housing conditions where there is no active or effective vector-control to Trypanosoma cruzi reinfection as determined by Ministry of Health guideline of the respective country
* Subjects with clinical manifestations of Chagas' disease-related gastrointestinal dysfunction or serious manifestations of acute Chagas' disease
* Immuno-compromised subjects (e.g. with human immunodeficiency virus or treated with immunosuppressive drugs)
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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La Plata, Buenos Aires, Argentina

Site Status

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Site Status

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Site Status

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Site Status

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Site Status

San Salvador de Jujuy, Jujuy Province, Argentina

Site Status

Posadas, Misiones Province, Argentina

Site Status

Rosario, Santa Fe Province, Argentina

Site Status

Corrientes, , Argentina

Site Status

Formosa, , Argentina

Site Status

La Rioja, , Argentina

Site Status

Mendoza, , Argentina

Site Status

Mendoza, , Argentina

Site Status

Salta, , Argentina

Site Status

Salta, , Argentina

Site Status

San Juan, , Argentina

Site Status

San Miguel de Tucumán, , Argentina

Site Status

Santiago del Estero, , Argentina

Site Status

Cochabamba, , Bolivia

Site Status

Punata, , Bolivia

Site Status

Tarija, , Bolivia

Site Status

Soledad, Atlántico, Colombia

Site Status

Yopal, Casanare Department, Colombia

Site Status

Santa Marta, Magdalena Department, Colombia

Site Status

Floridablabca, Santander Department, Colombia

Site Status

Countries

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Argentina Bolivia Colombia

References

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Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C. Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease. Am J Trop Med Hyg. 1998 Oct;59(4):526-9. doi: 10.4269/ajtmh.1998.59.526.

Reference Type RESULT
PMID: 9790423 (View on PubMed)

de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, Almeida IC, de Andrade SS, de Andrade JG, Martelli CM. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet. 1996 Nov 23;348(9039):1407-13. doi: 10.1016/s0140-6736(96)04128-1.

Reference Type RESULT
PMID: 8937280 (View on PubMed)

Altcheh J, Castro L, Dib JC, Grossmann U, Huang E, Moscatelli G, Pinto Rocha JJ, Ramirez TE; CHICO Study Group. Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO). PLoS Negl Trop Dis. 2021 Jan 7;15(1):e0008912. doi: 10.1371/journal.pntd.0008912. eCollection 2021 Jan.

Reference Type RESULT
PMID: 33412557 (View on PubMed)

Rivero R, Esteva MI, Huang E, Colmegna L, Altcheh J, Grossmann U, Ruiz AM; CHICO and CHICO SECURE Study Groups. ELISA F29 -A therapeutic efficacy biomarker in Chagas disease: Evaluation in pediatric patients treated with nifurtimox and followed for 4 years post-treatment. PLoS Negl Trop Dis. 2023 Jun 23;17(6):e0011440. doi: 10.1371/journal.pntd.0011440. eCollection 2023 Jun.

Reference Type DERIVED
PMID: 37352322 (View on PubMed)

Altcheh J, Sierra V, Ramirez T, Pinto Rocha JJ, Grossmann U, Huang E, Moscatelli G, Ding O. Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE). Antimicrob Agents Chemother. 2023 Apr 18;67(4):e0119322. doi: 10.1128/aac.01193-22. Epub 2023 Mar 28.

Reference Type DERIVED
PMID: 36975790 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2022-001504-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16027

Identifier Type: -

Identifier Source: org_study_id

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