NCT01489228

Brief Summary

This study will assess the safety and efficacy of E1224, a pro-drug of ravuconazole, in individuals with chronic indeterminate Chagas disease recruited in research centres in Tarija and Cochabamba, Bolivia.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
230

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2011

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2011

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

November 24, 2011

Completed
15 days until next milestone

First Posted

Study publicly available on registry

December 9, 2011

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2012

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
Last Updated

December 21, 2011

Status Verified

December 1, 2011

Enrollment Period

1.2 years

First QC Date

November 24, 2011

Last Update Submit

December 19, 2011

Conditions

Chronic Chagas Disease, Indeterminate

Keywords

Chagas Disease

Outcome Measures

Primary Outcomes (1)

  • Serial negative qualitative Polymerase Chain Reaction (PCR) results (3 negative PCR results from 3 samples to be collected over 7 days) as a measure of parasitological cure at end of treatment

    To determine whether at least one of three dosing regimens of orally administered E1224 is more efficacious than placebo in individuals with chronic indeterminate CD, by determining the number of patients who convert from positive to negative in serial, qualitative PCR test results

    Day 65 (end of treatment)

Secondary Outcomes (10)

  • Consistently negative serial qualitative PCR as a measure of sustained parasitological eradication

    4, 6 and 12 months follow-up

  • Qualitative PCR as a measure of parasite eradication

    Day 8, 15, 36 , 65 and at 4, 6 and 12 months follow-up

  • Quantitative PCR as a measure of change in parasite load over time

    Day 8, 15, 36, 65 and at 4, 6 and 12 months follow-up

  • Incidence of serological conversion to negative and changes in titers over time as measured by conventional and non-conventional serologies

    Day 65 and at 4, 6 and 12 months after treatment

  • Changes in the levels of biomarkers over time: brain natriuretic peptide, troponin T, selected prothrombotic factors, lytic antibodies, apolipoprotein A1 and multiplex serodiagnostic assay

    Day 36 , 65 and at 4, 6 and 12 months follow-up

  • +5 more secondary outcomes

Study Arms (5)

High Dose E1224

EXPERIMENTAL

High Dose (HD - 8weeks) Group

Drug: E1224

Low Dose E1224

EXPERIMENTAL

Low Dose (LD - 8 weeks) Group

Drug: E1224

Short Dose E1224

EXPERIMENTAL

Short Dose (SD - 4 weeks) Group

Drug: E1224

Placebo

PLACEBO COMPARATOR

Placebo (8 weeks) Group

Drug: Placebo

Benznidazol

ACTIVE COMPARATOR

BZN (Laboratório do Estado de Pernambuco -LAFEPE, tablet 100mg), 5 mg/Kg/day PO divided in two daily doses, for 60 days

Drug: Benznidazole

Interventions

E1224DRUG

100 mg tablets

Also known as: E1224 (prodrug for active ingredient Ravuconazole)
High Dose E1224Low Dose E1224Short Dose E1224
BenznidazoleDRUG

100mg tablets

Also known as: Benznidazole (N-benzil-2-nitro-1-imidazolacetamida)
Benznidazol
PlaceboDRUG

tablets

Placebo

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Confirmed diagnosis of T. cruzi infection by serial qualitative PCR AND Conventional serology
  • Women in reproductive age must have a negative serum pregnancy test at screening, must not be breastfeeding, and consistently use and/or have partner consistently use an adequate contraceptive method
  • Normal ECG at screening

You may not qualify if:

  • Abnormal laboratory test values at screening for the following parameters: total White Blood Cells (WBC) count, platelet count, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, or creatinine; or gamma-glutamyl transferase (GGT)
  • History of alcohol abuse or any other drug addiction (as specified in the Study Manual of Operations)
  • Any condition that prevents the patient from taking oral medication
  • Any concomitant use of antimicrobial or antiparasitic agents

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Plataforma de Atención Integral a los Pacientes con Enfermidad de Chagas

Cochabamba, Departamento de Cochabamba, Bolivia

RECRUITING

Plataforma de Atención Integral a los Pacientes con Enfermidad de Chagas

Tarija, Tarija Department, Bolivia

RECRUITING

Related Publications (3)

  • De Salazar PM, Sosa-Estani S, Salvador F, Sulleiro E, Sanchez-Montalva A, Ribeiro I, Molina I, Buckee CO. Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease. PLoS Negl Trop Dis. 2022 Nov 21;16(11):e0010828. doi: 10.1371/journal.pntd.0010828. eCollection 2022 Nov.

    PMID: 36409773DERIVED

  • Parrado R, Ramirez JC, de la Barra A, Alonso-Vega C, Juiz N, Ortiz L, Illanes D, Torrico F, Gascon J, Alves F, Flevaud L, Garcia L, Schijman AG, Ribeiro I. Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas Disease. Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01191-18. doi: 10.1128/AAC.01191-18. Print 2019 Feb.

    PMID: 30509941DERIVED

  • Torrico F, Gascon J, Ortiz L, Alonso-Vega C, Pinazo MJ, Schijman A, Almeida IC, Alves F, Strub-Wourgaft N, Ribeiro I; E1224 Study Group. Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial. Lancet Infect Dis. 2018 Apr;18(4):419-430. doi: 10.1016/S1473-3099(17)30538-8. Epub 2018 Jan 16.

    PMID: 29352704DERIVED

Related Links

MeSH Terms

Conditions

Chagas Disease

Interventions

Prodrugsbenzonidazole

Condition Hierarchy (Ancestors)

TrypanosomiasisEuglenozoa InfectionsProtozoan InfectionsParasitic DiseasesInfectionsVector Borne Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

  • Isabela Ribeiro, MD

    Drugs for Neglected Diseases initiative

    STUDY DIRECTOR

  • Faustino Torrico, PhD

    Universidad Mayor San Simón. Cochabamba, Bolivia.

    PRINCIPAL INVESTIGATOR

  • Joaquim Gascón, PhD

    CRESIB - Centre de Recerca en Salut Internacional de Barcelona, Spain.

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabiana P Alves, PhD

CONTACT

+552122152941falves@dndi.org

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 24, 2011

First Posted

December 9, 2011

Study Start

June 1, 2011

Primary Completion

August 1, 2012

Study Completion

December 1, 2013

Last Updated

December 21, 2011

Record last verified: 2011-12

Locations

BO(2)