Back to resultsProspective Study of a Pediatric Nifurtimox Formulation for Chagas' Disease
Primary Purpose
Chagas Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Nifurtimox (Lampit, BAYA2502)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chagas Disease
Eligibility Criteria
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Nifurtimox 60 days / Arm 1
Nifurtimox 30 days / Arm 2
Arm Description
Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)
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)
Outcomes
Primary Outcome Measures
Percentage of Participants Cured
Cure is defined as sero-reduction (in subjects ≥8 months to <18 years of age at randomization) or sero-conversion (in all subjects). Sero-reduction is defined as a ≥20% reduction in optical density [OD]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G (IgG) concentration measured by two conventional ELISA serology tests.
Subjects who have missing conventional serology results at the 12 month time point were treated as failures (ie, no cure).
For the primary objective in the study, superiority over placebo was confirmed if the lower limit of the 95% Confidence Interval (CI) for the nifurtimox (60-day regimen) cure rate is greater than 16%, the larger of the upper limits of the 95% CIs from the two publications.
Incidence Rate of Seronegative Conversion for Subjects Received at Least One Dose of the 60-day Nifurtimox Treatment Regimen.(Part 2)
Seronegative conversion measured by two types of assay (recombinant ELISA and indirect hemagglutination assay [IHA]) in subjects who were randomized and received at least one dose of the 60-day nifurtimox treatment regimen.
Secondary Outcome Measures
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 1
The evaluation was based on clinical examinations.
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3
The evaluation was based on clinical examinations.
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 6
The evaluation was based on clinical examinations.
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8
The evaluation was based on clinical examinations.
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 9
The evaluation was based on clinical examinations.
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 10
The evaluation was based on clinical examinations.
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 11
The evaluation was based on clinical examinations.
Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age)
Number of Subjects With a Positive Serological Response Using Non-conventional Enzyme-linked Immunosorbent Assay-F29 (ELISAF29) Test
The non-conventional ELISA-F29 test is considered an early marker of treatment efficacy in chronic Chagas disease.
Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results
The qPCR is molecular technique, considered a tool to diagnose acute and congenital Chagas disease, as well as a marker to measure treatment failure when demonstrating positive (detectable) results
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TEAEs comprised events which first occurred or worsened at or after first application of study drug during the course of the study up to and including 7 days after last application of study drug
Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment (Part 1)
The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment (Part 1)
The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment (Part 1)
The number analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. Subjects with missing or high abnormal values at baseline are not included in the number analyzed.
The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment (Part 1)
The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
Number of Subjects With Treatment-emergent High Coagulation Abnormalities by Treatment (Part 1)
The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
Number of Subjects With Treatment-emergent Low Coagulation Abnormalities by Treatment (Part 1)
The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
Number of Subjects With Abnormal Urinalysis Findings Considered as Clinically Significant or Reported as Adverse Events (AEs)
Urinalysis was performed and the following parameters evaluated: bilirubin, blood (red blood cells, white blood cells), chorionic gonadotropin β, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, and urobilinogen.
Number of Subjects With Abnormal ECG Findings Considered as Clinically Significant by Investigators (Part 1)
Clinical significance of abnormal ECG was based on the judgement of the investigator
Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline (Part 1)
Systolic Blood Pressure
Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline (Part 1)
Diastolic Blood Pressure
Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline (Part 1)
Respiratory Rate
Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline (Part 1)
Heart Rate
Mean Changes in Vital Signs(Temperature) Between the Treatment Groups From Baseline (Part 1)
Temperature
Nifurtimox Concentration Over Time in Plasma at Visit 2 (Part 1)
Measured in sub-population.
Nifurtimox Concentration Over Time in Plasma at Visit 3 (Part 1)
Measured in sub-population.
Nifurtimox Concentration Over Time in Plasma at Visit 6 (Part 1)
Measured in sub-population.
Nifurtimox Concentration Over Time in Plasma at Visit 8 (Part 1)
Measured in sub-population.
Incidence of Seronegative Conversion Received at Least One Dose of the 30-day Nifurtimox Treatment Regimen. (Part 2)
Measured once per year by two types of assays (recombinant ELISA and IHA) in subjects received at least one dose of 30-day nifurtimox treatment regimen.
Proportion of Responders With Seronegative Conversion and no Evidence of Cardiomyopathy (Part 2)
Seronegative conversion measured by two types of assays (recombinant ELISA and IHA). Cardiomyopathy as evaluated by electrocardiogram.
Antibody Titer in Plasma Over Time in All Subjects (Part 2)
Measured once per year by recombinant ELISA and total purified antigen ELISA in subjects treated either with the 60- or 30-day nifurtimox treatment regimen.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02625974
Brief Title
Prospective Study of a Pediatric Nifurtimox Formulation for Chagas' Disease
Official Title
Prospective, Historically Controlled Study to Evaluate the Efficacy and Safety of a New Pediatric Formulation of Nifurtimox in Children Aged 0 to 17 Years With Chagas' Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
January 27, 2016 (Actual)
Primary Completion Date
July 25, 2018 (Actual)
Study Completion Date
August 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study consists of two parts. Part I (CHICO) was designed to develop a better understanding of the efficacy, safety and pharmacokinetics of nifurtimox in children with a diagnosis of Chagas' disease (Trypanosoma cruzi infection) using pediatric formulations. Part II (CHICO SECURE) was designed at request of the FDA to assess the incidence of sero-negative conversion in children with diagnosis of Chagas' disease treated with nifurtimox.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chagas Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
330 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nifurtimox 60 days / Arm 1
Arm Type
Experimental
Arm Description
Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)
Arm Title
Nifurtimox 30 days / Arm 2
Arm Type
Other
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Nifurtimox (Lampit, BAYA2502)
Intervention Description
For pediatric subjects with body weight ≤ 40 kg: dosage 10 to 20 mg/kg/day in three divided doses.
For pediatric subjects with body weight > 40 kg: 8 - 10 mg/kg/day in three divided doses.
60 days of nifurtimox treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
Percentage of Participants Cured
Description
Cure is defined as sero-reduction (in subjects ≥8 months to <18 years of age at randomization) or sero-conversion (in all subjects). Sero-reduction is defined as a ≥20% reduction in optical density [OD]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G (IgG) concentration measured by two conventional ELISA serology tests.
Subjects who have missing conventional serology results at the 12 month time point were treated as failures (ie, no cure).
For the primary objective in the study, superiority over placebo was confirmed if the lower limit of the 95% Confidence Interval (CI) for the nifurtimox (60-day regimen) cure rate is greater than 16%, the larger of the upper limits of the 95% CIs from the two publications.
Time Frame
At 12 months post-treatment
Title
Incidence Rate of Seronegative Conversion for Subjects Received at Least One Dose of the 60-day Nifurtimox Treatment Regimen.(Part 2)
Description
Seronegative conversion measured by two types of assay (recombinant ELISA and indirect hemagglutination assay [IHA]) in subjects who were randomized and received at least one dose of the 60-day nifurtimox treatment regimen.
Time Frame
Up to 4 years after end of treatment
Secondary Outcome Measure Information:
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 1
Description
The evaluation was based on clinical examinations.
Time Frame
At Visit 1 (before treatment started)
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3
Description
The evaluation was based on clinical examinations.
Time Frame
Up to 7 days (Visit 3)
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 6
Description
The evaluation was based on clinical examinations.
Time Frame
Up to 30 days (Visit 6)
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8
Description
The evaluation was based on clinical examinations.
Time Frame
Up to 60 days (Visit 8) end of treatment
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 9
Description
The evaluation was based on clinical examinations.
Time Frame
Up to 90 days (Visit 9) post treatment
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 10
Description
The evaluation was based on clinical examinations.
Time Frame
Up to 240 days (Visit 10) post treatment
Title
Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 11
Description
The evaluation was based on clinical examinations.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age)
Time Frame
Up to 90 days (Visit 9) post-treatment
Title
Number of Subjects With a Positive Serological Response Using Non-conventional Enzyme-linked Immunosorbent Assay-F29 (ELISAF29) Test
Description
The non-conventional ELISA-F29 test is considered an early marker of treatment efficacy in chronic Chagas disease.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results
Description
The qPCR is molecular technique, considered a tool to diagnose acute and congenital Chagas disease, as well as a marker to measure treatment failure when demonstrating positive (detectable) results
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
TEAEs comprised events which first occurred or worsened at or after first application of study drug during the course of the study up to and including 7 days after last application of study drug
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment (Part 1)
Description
The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment (Part 1)
Description
The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment (Part 1)
Description
The number analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. Subjects with missing or high abnormal values at baseline are not included in the number analyzed.
The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment (Part 1)
Description
The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent High Coagulation Abnormalities by Treatment (Part 1)
Description
The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Treatment-emergent Low Coagulation Abnormalities by Treatment (Part 1)
Description
The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment.
The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Abnormal Urinalysis Findings Considered as Clinically Significant or Reported as Adverse Events (AEs)
Description
Urinalysis was performed and the following parameters evaluated: bilirubin, blood (red blood cells, white blood cells), chorionic gonadotropin β, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, and urobilinogen.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Number of Subjects With Abnormal ECG Findings Considered as Clinically Significant by Investigators (Part 1)
Description
Clinical significance of abnormal ECG was based on the judgement of the investigator
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline (Part 1)
Description
Systolic Blood Pressure
Time Frame
Baseline and up to 420 days (Visit 11) post-treatment
Title
Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline (Part 1)
Description
Diastolic Blood Pressure
Time Frame
Baseline and up to 420 days (Visit 11) post-treatment
Title
Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline (Part 1)
Description
Respiratory Rate
Time Frame
Baseline and up to 420 days (Visit 11) post-treatment
Title
Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline (Part 1)
Description
Heart Rate
Time Frame
Baseline and up to 420 days (Visit 11) post-treatment
Title
Mean Changes in Vital Signs(Temperature) Between the Treatment Groups From Baseline (Part 1)
Description
Temperature
Time Frame
Baseline and up to 420 days (Visit 11) post-treatment
Title
Nifurtimox Concentration Over Time in Plasma at Visit 2 (Part 1)
Description
Measured in sub-population.
Time Frame
At Visit 2 (Day 1): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
Title
Nifurtimox Concentration Over Time in Plasma at Visit 3 (Part 1)
Description
Measured in sub-population.
Time Frame
At Visit 3 (Day 7): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
Title
Nifurtimox Concentration Over Time in Plasma at Visit 6 (Part 1)
Description
Measured in sub-population.
Time Frame
At Visit 6 (Day 30): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
Title
Nifurtimox Concentration Over Time in Plasma at Visit 8 (Part 1)
Description
Measured in sub-population.
Time Frame
At Visit 8 (Day 60): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
Title
Incidence of Seronegative Conversion Received at Least One Dose of the 30-day Nifurtimox Treatment Regimen. (Part 2)
Description
Measured once per year by two types of assays (recombinant ELISA and IHA) in subjects received at least one dose of 30-day nifurtimox treatment regimen.
Time Frame
Up to 4 years after end of treatment
Title
Proportion of Responders With Seronegative Conversion and no Evidence of Cardiomyopathy (Part 2)
Description
Seronegative conversion measured by two types of assays (recombinant ELISA and IHA). Cardiomyopathy as evaluated by electrocardiogram.
Time Frame
Up to 4 years after end of treatment
Title
Antibody Titer in Plasma Over Time in All Subjects (Part 2)
Description
Measured once per year by recombinant ELISA and total purified antigen ELISA in subjects treated either with the 60- or 30-day nifurtimox treatment regimen.
Time Frame
Up to 4 years after end of treatment
Other Pre-specified Outcome Measures:
Title
Number of Subjects Cured With 60-day Regimen Compared With Historical Active Control (Benznidazole)
Description
This exploratory efficacy analysis evaluated the cure rate assessed as seroconversion of nifurtimox after 1-year post-treatment follow-up with that of published data for benznidazole (Sosa Estani et al. 1998 and de Andrade et al. 1996) at 4- and 3-year post-treatment follow-up, respectively, used as historical control.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Relationship of Conventional Serology (Total Purified Antigen ELISA) and qPCR Testing by Visit (Part 1)
Description
Using frequencies of matches and mismatches to assess agreement
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit (Part 1)
Description
Using frequencies of matches and mismatches to assess agreement
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit (Part 1)
Description
Using frequencies of matches and mismatches to assess agreement
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Relationship of Conventional Serology (ELISA) to Indirect Hemagglutination Assay (IHA) Results
Description
Sero-reduction is defined as a => 20% reduction in optical density [OD]) using two conventional ELISA serology tests in subjects => 8 months to < 18 years of age at randomization; Others: reactive results that are not sero-reduction in subjects => 8 months to < 18 years of age at randomization; or reactive results in subjects < 8 months of age at randomization.
Time Frame
Up to 420 days (Visit 11) post-treatment
Title
Relationship Between Conventional ELISA Results in Terms of Cure or No Cure and IHA Results in All Patients
Description
Cure is defined as sero-reduction (in subjects => 8 months to < 18 years of age at randomization) or sero-conversion (in all subjects).
Sero-reduction is defined as a => 20% reduction in optical density [OD]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G [IgG] concentration measured by two conventional ELISA serology tests.
Time Frame
Up to 420 days (Visit 11) post-treatment
10. Eligibility
Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
La Plata
State/Province
Buenos Aires
ZIP/Postal Code
1900
Country
Argentina
City
Buenos Aires
State/Province
Ciudad Auton. De Buenos Aires
ZIP/Postal Code
1281
Country
Argentina
City
Buenos Aires
State/Province
Ciudad Auton. De Buenos Aires
ZIP/Postal Code
C1270AAN
Country
Argentina
City
Buenos Aires
State/Province
Ciudad Auton. De Buenos Aires
ZIP/Postal Code
C1425AGP
Country
Argentina
City
Buenos Aires
State/Province
Ciudad Auton. De Buenos Aires
ZIP/Postal Code
C1425EFD
Country
Argentina
City
San Salvador de Jujuy
State/Province
Jujuy
ZIP/Postal Code
4600
Country
Argentina
City
Posadas
State/Province
Misiones
Country
Argentina
City
Rosario
State/Province
Santa Fe
ZIP/Postal Code
2000
Country
Argentina
City
Corrientes
ZIP/Postal Code
W3400CBI
Country
Argentina
City
Formosa
ZIP/Postal Code
P3600HZL
Country
Argentina
City
La Rioja
Country
Argentina
City
Mendoza
ZIP/Postal Code
5500
Country
Argentina
City
Mendoza
ZIP/Postal Code
5535
Country
Argentina
City
Salta
ZIP/Postal Code
4400
Country
Argentina
City
Salta
ZIP/Postal Code
A4400ESE
Country
Argentina
City
San Juan
ZIP/Postal Code
5400
Country
Argentina
City
Santiago del Estero
ZIP/Postal Code
4202
Country
Argentina
City
Tucuman
ZIP/Postal Code
4000
Country
Argentina
City
Cochabamba
Country
Bolivia
City
Punata
Country
Bolivia
City
Tarija
Country
Bolivia
City
Barranquilla
State/Province
Atlántico
Country
Colombia
City
Yopal
State/Province
Casanare
ZIP/Postal Code
0
Country
Colombia
City
Santa Marta
State/Province
Magdalena
ZIP/Postal Code
0
Country
Colombia
City
Floridablanca
State/Province
Santander
Country
Colombia
12. IPD Sharing Statement
Citations:
PubMed Identifier
9790423
Citation
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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.
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http://www.clinicaltrialsregister.eu/
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https://clinicaltrials.bayer.com/
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Learn more about this trial
Prospective Study of a Pediatric Nifurtimox Formulation for Chagas' Disease
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