Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Double Blind Clinical Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 910
- Locations
- 1
- Primary Endpoint
- Development of heart failure
Study Overview
Brief Summary
The purpose of this study is:
- -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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 20 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Benznidazole
Benznidazole pills of 100 mg, dose 5 mg/Kg/day, twice a day during 60 days
Intervention: Benznidazole (Drug)
Placebo
Placebo pills 100 mg, dose 5mg/Kg/day, twice a day, during 60 days
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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
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
Secondary Outcomes
- Enlargement of the left ventricle (LV) detected by echocardiography.(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)
- Changes of the secondary objectives during RCT development. New single endpoints(Since October 2011 during 18 months)
- Serological negativization(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)
- Changes in clinical stage in chronic Chagas disease(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)
- Development and validation of RT-PCR(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)
- Electrocardiographic endpoints. New development of permanent changes in the electrocardiographic(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)
- New Heart Failure(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)
- Stroke(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)
- Combined clinical endpoints:(Since October 2011 during 18 months)
Investigators
Adelina Rosa Riarte
Adelina Rosa Riarte MD
Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben