Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Clinical Trial (TRAENA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02386358
Recruitment Status : Completed
First Posted : March 11, 2015
Last Update Posted : March 11, 2015
Sponsor:
Collaborators:
National Council of Scientific and Technical Research, Argentina
Pan American Health Organization
Becas Carrillo Oñativia, Ministerio de Salud, Argentina
Drugs for Neglected Diseases
Information provided by (Responsible Party):
Adelina Rosa Riarte, Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben

Tracking Information
First Submitted Date  ICMJE January 19, 2015
First Posted Date  ICMJE March 11, 2015
Last Update Posted Date March 11, 2015
Study Start Date  ICMJE March 1999
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2015)
  • Cardiovascular Mortality [ Time Frame: Time to event: from date of randomization until the date of first documented progression or date of death from any cause up to 10 years of follow-up ]
    Sudden death, unexpectedly in time and in its presentation,preceded by the abrupt loss of consciousness within a maximum of one hour of the onset of symptoms,when it happened during sleep or unexpectedly in a patient was stable until then. Related Death, when presented in a patient with signs of progressive heart failure.Ischemic or Hemorrhagic Stroke
  • Development of heart failure [ Time Frame: Time to event: from date of randomization until the date of first documented progression of heart failure up to 10 years of follow-up ]
    Dyspnea is evaluated according to the classification of the New York Heart Association (NYHA),gallop rhythm, jugular venous distension, crackles in the lungs, edema or pleural effusion,hepatomegaly
  • Severe arrhythmias with hemodynamic compromise or pacemaker implant or Implantable cardiac defibrillator [ Time Frame: Time to event: from date of randomization until the date of first documented progression up to 10 years of follow-up ]
    Sustained ventricular tachycardia, atrioventricular block, trifascicular block, Atrial fibrillation
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2015)
  • Electrocardiographic endpoints. New development of permanent changes in the electrocardiographic [ Time Frame: Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up ]
    • Stable sinus bradycardia (<50 beats / min)
    • Auriculoventricular blocks of 2nd and 3rd degree
    • Left anterior hemi-block
    • Complete right bundle branch block
    • Atrial flutter or fibrillation
    • Sustained ventricular tachycardia
  • Changes in clinical stage in chronic Chagas disease [ Time Frame: Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up ]
    Clinical progression
  • Enlargement of the left ventricle (LV) detected by echocardiography. [ Time Frame: Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up ]
    Clinical Progression
  • New Heart Failure [ Time Frame: Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up ]
    Clinical Progression
  • Stroke [ Time Frame: Time to event: from date of randomization until the date of first documented as defined in the secondary outcome up to 10 years of follow-up ]
    Clinical progression
  • Serological negativization [ Time Frame: time to event: from the date of randomization to the date of the first documented serological negativization that persists until 10 years of follow-up ]
    by ELISA F29 vs. conventional serology as a late indicator of efficacy or therapeutic failure.
  • Development and validation of RT-PCR [ Time Frame: time to event: from the date of randomization to the date of the first documented no detectable RT-PCR that persists until 10 years of follow-up ]
    Demonstration of RT-PCR as an early indicator of efficacy or therapeutic failure.
  • Changes of the secondary objectives during RCT development. New single endpoints [ Time Frame: Since October 2011 during 18 months ]
    1. Any change in clinical stage 0 to II due to left ventricular enlargement demonstrated by echocardiogram, or I to III stage due to development of heart failure.
    2. Complete left branch block
      • 3. Atrial fibrillation
      • 4. Repetitive ventricular extrasystoles: doublets, triplets, bigemina, trigeminus, ventricular tachycardia
  • Combined clinical endpoints: [ Time Frame: Since October 2011 during 18 months ]
    • Right bundle branch block associated with left anterior hemi-block.
    • Parietal motility disorders of left ventricle by echocardiography (akinesia, hypokinesia, and dyskinesia) associated with impaired left ventricular systolic function.
    • Parietal motility disorders of left ventricle by echocardiogram (Akinesia, Hypokinesia, dyskinesia) and /or impaired LV systolic function associated with new electrocardiographic changes (complete left branch block, right bundle branch block, left anterior hemi-block, ventricular extrasystoles.
    • Occurrence of left ventricle aneurysm point by echocardiogram associated to ventricular arrhythmia (section 2.4.1.4.).
    • Occurrence of left ventricle aneurysm point by echocardiogram associated with depression of LV systolic function by echocardiography.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Clinical Trial
Official Title  ICMJE Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Double Blind Clinical Trial
Brief Summary

The purpose of this study is:

  1. -to determine whether benznidazole (BZN) will be able to modify the natural evolution of chronic Chagas disease in adult patients by means of a randomized, double-blind clinical trial (RCT).

    Also:

  2. -to validate therapeutic efficacy with new methods, such as recombinant antigen F29 of Trypanosoma cruzi visualized by conventional ELISA, in the context of the RCT compared with conventional serology (CS)
  3. -to develop the real-time polymerase chain-reaction (RT-PCR) to quantify the parasite load as an early therapeutic effect.
  4. to determine the potential of such serological and parasitological methods as predictors of therapeutic effect or failure.
Detailed Description

Patients and Methods. Patients selected to be enrolled were born in Chagas disease endemic areas of Argentina and bordering countries such as Bolivia and Paraguay, whose current residence is in urban non endemic areas of Argentina. They were sorted by clinical stage: stage 0, 1, 2 and 3 according to a modified Kuschnir classification.1 Briefly, Stage 0 corresponds to patients only with reactive serology for Chagas disease; stage 1, patients with reactive serology plus electrocardiographic abnormalities; stage 2, patients with the abovementioned characteristics plus dilatation of left ventricle by echocardiography, and stage 3, patients with the abovementioned characteristics, plus cardiac failure.

The follow-up was performed every 4 months during the first 2 years, every 6 months in the 3rd and 4th year, and annually from then on until the end of the study in 2012.

The safety of TRAENA was controlled at days 25 and 45 intra-treatment by means of laboratory tests and clinical evaluation, and at any time that an adverse event was apparent in patients.

Adherence to medication administration was verified by means of a booklet where the patient recorded the daily intake of medication and any physical abnormality that appeared during the time they were taking of medicine. Adherence was controlled by a surveillance and recovery system which consisted of telephone calls, telegrams, letters or home visits that was termed "active monitoring", which was immediately applied to the control visit when the patient did not attend the corresponding schedule control.

Telephone calls were the most useful tool to recover adherence to monitoring. Patients were assigned to BZN or Placebo treatment by an investigator independent from the research group. Prior to randomization, a pre randomization stratification was performed according to prognostic factors based on clinical stages of Chagas disease.

A database was designed to be used as the registry for the whole study. Demographic, epidemiologic, serologic, parasitological and clinical variables were used in its design, and were registered pre treatment, intra treatment and post treatment throughout the monitoring. Medical records were the primary documents for the registry, where all the variables were recorded manually. Based on the data, variables were registered on a daily basis and a random weekly check was conducted on the data against the medical records. Our Standard Operating Procedure was based on the following procedures: patient screening, selection and coding, sample collection, serum bank, DNA sample storage, monitoring systematization, surveillance systems to recover patients who had discontinued monitoring, etc.

In October 2011 the Base Data Monitoring Board for the last Interim Analysis, recommended an addendum modifying the secondary outcomes, adding simple and combined events. These events were characterized only by electrocardiographic abnormalities or associated to echocardiographic ones. These events were evaluated up April 2013.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chagas Disease
Intervention  ICMJE
  • Drug: Benznidazole
    Benznidazole at a dose 5 mg/Kg/day until 60 days have been completed or development of non-acceptable toxicity-
    Other Name: Radanil (Roche Laboratory)
  • Drug: Placebo
    Placebo at a dose 5 m/Kg/day until 60 days
    Other Name: Placebo pills
Study Arms  ICMJE
  • Active Comparator: Benznidazole
    Benznidazole pills of 100 mg, dose 5 mg/Kg/day, twice a day during 60 days
    Intervention: Drug: Benznidazole
  • Placebo Comparator: Placebo
    Placebo pills 100 mg, dose 5mg/Kg/day, twice a day, during 60 days
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2015)
910
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients living in urban areas
  • Reactive to at least 2 for serological test performed in Fatala Chaben Institute (ELISA and IFI) ,
  • Patients who agreed to be part of this protocol through informed consent form signed

Exclusion Criteria:

  • Patients with chronic Chagas disease who have received prior treatment with benznidazole
  • Other cardiomyopathies : idiopathic , alcoholic , peripartum myocarditis, secondary to coronary artery disease, valve disease, hypertension, restrictive, hypertrophic or congenital
  • Chronic renal disease
  • Bleeding disorders
  • History of liver disease or current liver disease ,
  • Any other severe clinical disease that decreases their life expectancy
  • History of severe allergies
  • Pregnant patients
  • Patients who have not signed the informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02386358
Other Study ID Numbers  ICMJE TRAENA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Adelina Rosa Riarte, Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben
Study Sponsor  ICMJE Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben
Collaborators  ICMJE
  • National Council of Scientific and Technical Research, Argentina
  • Pan American Health Organization
  • Becas Carrillo Oñativia, Ministerio de Salud, Argentina
  • Drugs for Neglected Diseases
Investigators  ICMJE
Principal Investigator: Adellina R Riarte, MD Chief of Clinical, Pathology and Treatment Department
PRS Account Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP