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Shorter Benznidazole Regimens Compared to the Standard Regimen for Chagas Disease (NuestroBen)

Primary Purpose

Chagas Disease

Status
Recruiting
Phase
Phase 3
Locations
Argentina
Study Type
Interventional
Intervention
Short regimen of benznidazole
Short treatment with benznidazole
Standard treatment with benznidazole
Sponsored by
Laboratorio Elea Phoenix S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chagas Disease focused on measuring Chagas disease, Benznidazole, Trypanosoma Cruzi, Standar treatment, Short treatment

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Screening Criteria:

  • Signed informed consent form.
  • Between ≥18 and ≤60 years of age.
  • Diagnosis of T. cruzi infection by conventional serology (a minimum of two positive tests).
  • Ability to comply with all exams and specific protocol visits. Having a permanent address.
  • Not presenting signs or symptoms of chronic cardiac and/or digestive forms of Chagas disease, defined according to national guidelines.
  • No prior history of mental disorders or suicidal tendencies.
  • Not suffering from acute or chronic illnesses that, in the Investigator's discretion, may interfere with the evaluation of the efficacy or safety of the investigational product (such as acute infections, a history of HIV infection, or liver or kidney diseases that have required treatment).
  • Not having received a formal indication not to take BZN (contraindication, according to the Summary of Product Characteristics - SmPC). Contraindications to BZN basically include hypersensitivity to the active substance and its excipients. According to the SmPC for BZN, subjects will be advised not to drink alcoholic beverages during treatment.
  • No prior history of hypersensitivity, allergy, or serious adverse reactions to any of the nitroimidazole compounds and/or its components.
  • Have not previously undergone antiparasitic treatment for Chagas disease.
  • No prior history of drug abuse or alcoholism.
  • Not suffering from any disease that prevents subjects from consuming oral medication.

Inclusion Criteria:

After the screening period, subjects must meet ALL the inclusion criteria detailed below for recruitment:

Confirmation of the diagnosis of T. cruzi infection by:

Serial qualitative PCR (three samples collected on the same day, at least one of which must be positive)

AND

Conventional serology (a minimum of two tests must be reactive).

  • Women of childbearing potential must have a negative pregnancy result at the time of inclusion, must not be breast-feeding, and must use a highly effective method of contraception until completion of the trial.
  • Normal ECG (Heart rate: 50 -100 bpm; interval duration: PR ≤ 200 msec, QRS ≤120 msec, and QTc ≥ 350 msec and ≤ 450 msec) at screening.
  • Normal echocardiogram (left ventricular diastolic diameter (LVDD) <= 55 mm, absence of Microaneurysm or tip aneurysm, Hypo or generalized akinesia, Systolic dysfunction (low fractional shortening and ejection fraction), and/or Mural thrombus).
  • Normal chest X-ray (Cardiac silhouette with index <0.5).

Exclusion Criteria:

The presence of any of the items below will exclude subjects from inclusion in the study:

  • Patient pregnant or intending to become pregnant during treatment and within 30 days of the last dose of study treatment.
  • Signs or symptoms of the chronic cardiac and/or digestive form of Chagas disease, defined according to national guidelines.
  • History of cardiomyopathy, heart failure, or ventricular arrhythmia.
  • History of digestive surgery or mega syndromes.
  • Acute or chronic disease that, in the Investigator's discretion, may interfere with the evaluation of the efficacy or safety of the investigational product (such as acute infection, history of HIV infection, or liver or kidney disease that has required treatment).
  • Laboratory test values that are considered clinically significant or outside the allowable values, per CTCAE version 5.0 grade 1.
  • Disease that prevents subjects from consuming oral medication.
  • Subjects with a contraindication (known hypersensitivity) to any of the nitroimidazole compounds, e.g. metronidazole.
  • Subjects with a history of allergy (serious or not), allergic rash, asthma, intolerance, sensitivity or photosensitivity to any drug.
  • Concomitant use and/or consumption of allopurinol, antimicrobial and antiparasitic agents, herbal medicines, dietary supplements and energy drinks.
  • Scheduled surgery that may interfere with the conduct of the trial and/or with the treatment evaluation.
  • Inability to attend study visits, comply with treatment, and cooperate with study procedures.
  • Previous participation in a trial for the evaluation of the treatment of Chagas disease.
  • Simultaneous participation in another trial or within 3 months prior to screening for this trial (in accordance with national regulations).
  • Serious medical or psychiatric illness that increases the risk associated with study participation or that interferes with the interpretation of study results

Sites / Locations

  • Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"
  • Fundación Huésped
  • Hospital Francisco Javier Muñiz
  • Hospital Donación Francisco Santojanni
  • Instituto de Cardiología de Corrientes "Juana Francisca Cabral"Recruiting
  • Centro de Chagas y Patología Regional, Hospital Independencia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Short regimen of benznidazole 2 weeks

Short regimen of benznidazole 4 weeks

Standard treatment with benznidazole

Arm Description

Experimental: Short regimen of benznidazole Participants will receive an investigational treatment of benznidazole for 2 weeks. Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks.

Experimental: Short regimen of benznidazole Participants will receive an investigational treatment of benznidazole for 4 weeks. Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks.

Active Comparator: Standard treatment with benznidazole Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks

Outcomes

Primary Outcome Measures

Proportion of patients with sustained negativation of parasitemia according to the results of qualitative PCR tests
Sustained parasitological response will be determined by negative serial qualitative PCR results (two negative PCR results from three DNA extractions from a sample) from the end of treatment with the elimination of sustained parasitaemia until the end of 12 months' follow-up from the end of treatment.

Secondary Outcome Measures

Proportion of patients with negative parasitemia at 1, 4, 6 and 8 months follow-up form the end of treatment
Proportion of patients with negative parasitemia at 1, 4, 6 and 8 months follow-up form the end of treatment
Incidence and severity of adverse events
Incidence and severity of adverse events
Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption
Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption
Descriptions of patients adherence to treatment in each study arm.
describing the number of completed treatment in patients vs uncompleted treatment in patients

Full Information

First Posted
May 18, 2021
Last Updated
September 19, 2023
Sponsor
Laboratorio Elea Phoenix S.A.
Collaborators
Drugs for Neglected Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT04897516
Brief Title
Shorter Benznidazole Regimens Compared to the Standard Regimen for Chagas Disease
Acronym
NuestroBen
Official Title
Phase III Randomized,Multicenter Non-inferiority Study to Evaluate the Efficacy and Safety of Shorter Benznidazole Regimens Compared to the Standard Regimen to Treat Adult Patients With Chronic Chagas Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2021 (Actual)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Laboratorio Elea Phoenix S.A.
Collaborators
Drugs for Neglected Diseases

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Chagas disease, a parasitic infection caused by Trypanosoma cruzi, is endemic in much of Latin America and affects people throughout the world. Currently treatment with the only two drugs effective against the infection, benznidazole and nifurtimox, has significant limitations including frequent adverse effects in adult patients. However, timely treatment is key to achieving global objectives of controlling the disease. The standard treatment has a long duration (60 days). NuestroBen will test the hypothesis that shorter treatment regimens of 14 days and 28 days will be non-inferior to the standard 60-day treatment while improving the safety profile.
Detailed Description
Chagas disease is a vector-borne parasitic infection affecting an estimated 6 million people worldwide. Very few people have been able to access antiparasitic treatment for the disease, and about 20% of those who do initiate treatment are unable to complete it due to the long duration (2 months) and side effects associated with the current regimen. Benznidazole is one of only two drugs with proven efficacy against Trypanosoma cruzi, the parasite that causes the disease. An earlier Phase 2 clinical trial, BENDITA, indicated 89% of 30 patients treated with a shorter (2-week) regimen of benznidazole maintained sustained parasite clearance after 12 months of follow-up, with no discontinuations of treatment due to side effects. The current study will evaluate shorter treatment regimens with benznidazole in a Phase III clinical trial. NuestroBen will assess the efficacy and safety of 2-week and 4-week regimens of BZN (300 mg daily), compared to the standard treatment of BZN 300 mg daily for 8 weeks, in terms of reducing and eliminating the T. cruzi parasite in adults in the chronic phase of Chagas disease with the indeterminate form or mild cardiac progression. Efficacy will be measured through conversion from positive to negative parasitaemia according to the results of qualitative PCR tests from the end of treatment, and up to 12 months of follow-up from the end of treatment. Safety will be compared according to the frequency and severity of adverse events. Patients adherence to treatment in each study arm will also be described.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chagas Disease
Keywords
Chagas disease, Benznidazole, Trypanosoma Cruzi, Standar treatment, Short treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Phase III, open-label, prospective, controlled, multicenter, non-inferiority study to compare the efficacy of the Drug: 1. Short regimen of benznidazole :Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks. 2. Drug: Short regimen of benznidazole : Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks. And 3. Drug: Standard treatment with benznidazole : Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Short regimen of benznidazole 2 weeks
Arm Type
Experimental
Arm Description
Experimental: Short regimen of benznidazole Participants will receive an investigational treatment of benznidazole for 2 weeks. Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks.
Arm Title
Short regimen of benznidazole 4 weeks
Arm Type
Experimental
Arm Description
Experimental: Short regimen of benznidazole Participants will receive an investigational treatment of benznidazole for 4 weeks. Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks.
Arm Title
Standard treatment with benznidazole
Arm Type
Active Comparator
Arm Description
Active Comparator: Standard treatment with benznidazole Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Short regimen of benznidazole
Other Intervention Name(s)
Benznidazole 2 weeks
Intervention Description
Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Short treatment with benznidazole
Other Intervention Name(s)
Benznidazole 4 weeks
Intervention Description
Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Standard treatment with benznidazole
Other Intervention Name(s)
Benznidazole 8 weeks
Intervention Description
Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks
Primary Outcome Measure Information:
Title
Proportion of patients with sustained negativation of parasitemia according to the results of qualitative PCR tests
Description
Sustained parasitological response will be determined by negative serial qualitative PCR results (two negative PCR results from three DNA extractions from a sample) from the end of treatment with the elimination of sustained parasitaemia until the end of 12 months' follow-up from the end of treatment.
Time Frame
From the end of treatment, and up to 12 months of follow-up from the end of treatment.
Secondary Outcome Measure Information:
Title
Proportion of patients with negative parasitemia at 1, 4, 6 and 8 months follow-up form the end of treatment
Description
Proportion of patients with negative parasitemia at 1, 4, 6 and 8 months follow-up form the end of treatment
Time Frame
1, 4, 6 and 8 months from the end of treatment
Title
Incidence and severity of adverse events
Description
Incidence and severity of adverse events
Time Frame
From the end of treatment, and up to 12 months of follow-up from the end of treatment
Title
Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption
Description
Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption
Time Frame
From the end of treatment, and up to 12 months of follow-up from the end of treatment.
Title
Descriptions of patients adherence to treatment in each study arm.
Description
describing the number of completed treatment in patients vs uncompleted treatment in patients
Time Frame
2, 4 and 8 weeks
Other Pre-specified Outcome Measures:
Title
Incidence and severity of adverse events
Description
Incidence and severity of adverse events
Time Frame
From the end of treatment, and up to 12 months of follow-up from the end of treatment.
Title
Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption
Description
Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption
Time Frame
From the end of treatment, and up to 12 months of follow-up from the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria (Subjects must meet ALL the inclusion requirements listed below to enter the study): Signed informed consent form; Between ≥18 and ≤60 years of age; Weight ≥ 50 kg to ≤ 95 kg; Confirmation of the diagnosis of T. cruzi infection by conventional serology (a minimum of two tests must be reactive); Serial qualitative PCR (one blood sample divided in three DNA extractions, at least one of which must be positive); Women of childbearing potential must have a negative pregnancy result at the time of inclusion, must not be breast-feeding, and must use a highly effective method of contraception during study treatment and until 30 days after the last dose of study treatment or demonstrate permanent sterilization; Ability to comply with all exams and specific protocol visits; Having a permanent address; ECG criteria: (Heart rate: 50 -100 bpm or isolate sinus bradycardia from 41 to 59 beats/min; QRS ≤120 msec, and QTc ≥ 350 msec and ≤ 450 msec) at screening) or following findings belonging to non-severe chagasic cardiomyopathy: uncomplete right bundle branch block, Left anterior fascicular block, First-degree atrioventricular block, Low voltage. The abnormalities included are not exclusionary; Normal or minimal structural changes in echocardiogram (left ventricular diastolic diameter (LVDD) <= 55 mm, diastolic dysfunction, absence of Microaneurysm or tip aneurysm, absence of hypo or generalized akinesia, absence of Systolic dysfunction (low fractional shortening and ejection fraction), and/or absence of mural thrombus); Not presenting signs or symptoms of moderate- severe chronic cardiac and/or digestive forms of Chagas disease (criteria detailed in Study Manual and specific SOP); No prior history of mental disorders or suicidal tendencies; Not suffering from known acute or chronic illnesses at the moment of selection for the study that, in the Investigator's discretion, may interfere with the evaluation of the efficacy or safety of the investigational product (such as acute infections, immunosuppressive conditions, or liver or kidney diseases that have required treatment); Not having received a formal indication not to take BZN (contraindication, according to the Summary of Product Characteristics - SmPC); No prior history of hypersensitivity, allergy, or serious adverse reactions to any of the nitroimidazole compounds (including BNZ) and/or its components/excipients; Have not previously undergone antiparasitic treatment for T. cruzi infection; No prior history of drug abuse or alcoholism; Not suffering from any disease or condition that prevents subjects from consuming oral medication. Exclusion criteria (The presence of any of the items below will exclude subjects from inclusion in the study): Subject pregnant or intending to become pregnant during treatment and within 30 days of the last dose of study treatment; Signs or symptoms of the established (moderate- severe) chronic cardiac and/or digestive form of Chagas disease, or any ECG/ echocardiographic findings not included at Inclusion criteria; History of cardiomyopathy, heart failure, or severe ventricular arrhythmia; History of digestive surgery potentially related to Chagas Disease or megacolon / mega-esophagus; Acute or chronic disease that, in the Investigator's discretion, may interfere with the evaluation of the efficacy or safety of the investigational product (such as acute infection, history of immunosuppressive conditions, or liver or kidney disease that has required treatment); Laboratory test values that are considered clinically significant or outside the allowable values, per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1; Disease or clinical condition that prevents subjects from consuming oral medication; Subjects with a contraindication (known hypersensitivity) to any of the nitroimidazole compounds, e.g. metronidazole; Subjects with a history of allergy (serious or not), allergic rash, asthma, intolerance, sensitivity or photosensitivity; Concomitant use and/or consumption of allopurinol, antimicrobial and antiparasitic agents, herbal medicines, dietary supplements and energy drinks; Scheduled surgery that may interfere with the conduct of the trial and/or with the treatment evaluation; Inability to attend study visits, comply with treatment, and cooperate with study procedures; Previous participation in a trial for the evaluation of the treatment of T. cruzi infection; Simultaneous participation in another trial or within 3 months prior to screening for this trial (in accordance with national regulations). Subjects suffering from a serious medical or psychiatric illness that increases the risk associated with study participation or that interferes with the interpretation of study results should not be included.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carola Lombas, MD
Phone
(54) 11 44898300
Email
carola.lombas@elea.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tayná Marques, MSc
Phone
(55) 21 9978 40503
Email
tmarques@dndi.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sergio Sosa-Estani, MD
Organizational Affiliation
Drugs for Neglected Diseases
Official's Role
Study Director
Facility Information:
Facility Name
Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"
City
Buenos Aires
ZIP/Postal Code
C1097
Country
Argentina
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marisa Fernandez, MD
Email
marisa.fernandez@gmail.com
Facility Name
Fundación Huésped
City
Buenos Aires
ZIP/Postal Code
C1202ABB
Country
Argentina
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Patterson, MD
Email
patricia.patterson@huesped.org.ar
Facility Name
Hospital Francisco Javier Muñiz
City
Buenos Aires
ZIP/Postal Code
C1282A
Country
Argentina
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susana Lloveras, MD
Email
sclloveras@gmail.com
Facility Name
Hospital Donación Francisco Santojanni
City
Buenos Aires
ZIP/Postal Code
C1408INH
Country
Argentina
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pablo Scapellato, MD
Email
pscapel@intramed.net
Facility Name
Instituto de Cardiología de Corrientes "Juana Francisca Cabral"
City
Corrientes
ZIP/Postal Code
W3400
Country
Argentina
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
María del Carmen Bangher, MD
Email
mbangher@yahoo.com.ar
Facility Name
Centro de Chagas y Patología Regional, Hospital Independencia
City
Santiago Del Estero
ZIP/Postal Code
G4200
Country
Argentina
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Rosmiro, MD
Email
rosmirojfernandez@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data from the study will be made available upon request. Requests are evaluated by DNDi's scientific advisory committee. Interested researchers can contact DNDi for data access requests via email at ctdata@dndi.org. Researchers can also request data by completing the form available at https://www.dndi.org/category/clinical-trials/. In this data request form, researchers must confirm that they will share data and results with DNDi and will publish any results open access.
IPD Sharing Time Frame
Beginning 6 months after publication of study results
IPD Sharing Access Criteria
Beginning 6 months after publication of study results

Learn more about this trial

Shorter Benznidazole Regimens Compared to the Standard Regimen for Chagas Disease

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