Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Clinical Trial
Condition: Chagas Disease
MeSH terms: Chagas Disease
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Benznidazole; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Benznidazole at a dose 5 mg/Kg/day until 60 days have been completed or development of non-acceptable toxicity-; Placebo at a dose 5 m/Kg/day until 60 days
Other intervention name(s): Radanil (Roche Laboratory); Placebo pills
Intervention MeSH terms: Benzonidazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Chronic Chagas Disease; Randomized Clinical Trial double blind; Benznidazole vs Placebo; Adult patients