AzTrials
AzTrials

Chagas DiseasePhase 3TRAENANCT02386358

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

A Phase 3 study testing Benznidazole in people with Chagas Disease, run by Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben at 1 site in Argentina.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 20 to 55 years
Conditions the study is for
Chagas Disease
What is being tested?
Benznidazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
910 participants
Where
1 siteArgentina
Study dates
Mar 1999to Apr 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • History of severe allergies
  • Pregnant patients
  • Patients who have not signed the informed consent.

Trial locations and contacts

1 site in 1 country.

Argentina1 site

  • Instituto Nacional de Parasitología Dr Mario Fatala Chaben

    Ciudad Autónoma de Buenos Aires, Buenos Aires, 1063

Other trials in Argentina

About this study

Official title: Etiologic Treatment With Benznidazole in Adult Patients With Chronic Chagas Disease. A Randomized Double Blind Clinical Trial

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.
Read the 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.

Conditions
Chagas Disease
Being tested
Benznidazole, Placebo
Keywords
Chronic Chagas Disease, Randomized Clinical Trial double blind, Benznidazole vs Placebo, Adult patients
Medical subject headings
Chagas Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BenznidazoleDrug

    Also called Radanil (Roche Laboratory)

    Benznidazole at a dose 5 mg/Kg/day until 60 days have been completed or development of non-acceptable toxicity-

  • PlaceboDrug

    Also called Placebo pills

    Placebo at a dose 5 m/Kg/day until 60 days

Study groups in NCT02386358
Study groupRoleWhat they receive
BenznidazoleActive comparatorBenznidazole pills of 100 mg, dose 5 mg/Kg/day, twice a day during 60 days
Receives: Drug: Benznidazole
PlaceboPlacebo comparatorPlacebo pills 100 mg, dose 5mg/Kg/day, twice a day, during 60 days
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cardiovascular Mortality

    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

    Measured: 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

  2. Development of heart failure

    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

    Measured: Time to event: from date of randomization until the date of first documented progression of heart failure up to 10 years of follow-up

  3. Severe arrhythmias with hemodynamic compromise or pacemaker implant or Implantable cardiac defibrillator

    Sustained ventricular tachycardia, atrioventricular block, trifascicular block, Atrial fibrillation

    Measured: Time to event: from date of randomization until the date of first documented progression up to 10 years of follow-up

Secondary outcomes (9)

  1. Electrocardiographic endpoints. New development of permanent changes in the electrocardiographic

    • 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

    Measured: 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

  2. Changes in clinical stage in chronic Chagas disease

    Clinical progression

    Measured: 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

  3. Enlargement of the left ventricle (LV) detected by echocardiography.

    Clinical Progression

    Measured: 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

  4. New Heart Failure

    Clinical Progression

    Measured: 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

  5. Stroke

    Clinical progression

    Measured: 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

  6. Serological negativization

    by ELISA F29 vs. conventional serology as a late indicator of efficacy or therapeutic failure.

    Measured: 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

  7. Development and validation of RT-PCR

    Demonstration of RT-PCR as an early indicator of efficacy or therapeutic failure.

    Measured: 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

  8. Changes of the secondary objectives during RCT development. New single endpoints

    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

    Measured: Since October 2011 during 18 months

  9. Combined clinical endpoints:

    • 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.

    Measured: Since October 2011 during 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2015 (estimated)
  2. Study startMar 1999
  3. Primary completionDec 2012
  4. Study completionApr 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
910 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02386358
Sponsor's protocol ID
TRAENA
Acronym
TRAENA
Status last verified
Mar 2015
First submitted
19 Jan 2015
Last updated
11 Mar 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C. Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease. Am J Trop Med Hyg. 1998 Oct;59(4):526-9. doi: 10.4269/ajtmh.1998.59.526.

    PubMed 9790423

  • de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, Almeida IC, de Andrade SS, de Andrade JG, Martelli CM. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet. 1996 Nov 23;348(9039):1407-13. doi: 10.1016/s0140-6736(96)04128-1.

    PubMed 8937280

  • Viotti R, Vigliano C, Armenti H, Segura E. Treatment of chronic Chagas' disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J. 1994 Jan;127(1):151-62. doi: 10.1016/0002-8703(94)90521-5.

    PubMed 8273735

  • Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti A. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med. 2006 May 16;144(10):724-34. doi: 10.7326/0003-4819-144-10-200605160-00006.

    PubMed 16702588

  • Porcel BM, Bontempi EJ, Henriksson J, Rydaker M, Aslund L, Segura EL, Pettersson U, Ruiz AM. Trypanosoma rangeli and Trypanosoma cruzi: molecular characterization of genes encoding putative calcium-binding proteins, highly conserved in trypanosomatids. Exp Parasitol. 1996 Dec;84(3):387-99. doi: 10.1006/expr.1996.0127.

    PubMed 8948328

  • Kuschnir E, Sgammini H, Castro R, Evequoz C, Ledesma R, Brunetto J. [Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy]. Arq Bras Cardiol. 1985 Oct;45(4):249-56. No abstract available. Spanish.

    PubMed 3835868

  • Reyes PA, Vallejo M. Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection). Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004102. doi: 10.1002/14651858.CD004102.pub2.

    PubMed 16235350

  • Villar JC, Perez JG, Cortes OL, Riarte A, Pepper M, Marin-Neto JA, Guyatt GH. Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection. Cochrane Database Syst Rev. 2014 May 27;2014(5):CD003463. doi: 10.1002/14651858.CD003463.pub2.

    PubMed 24867876

  • Schijman AG, Bisio M, Orellana L, Sued M, Duffy T, Mejia Jaramillo AM, Cura C, Auter F, Veron V, Qvarnstrom Y, Deborggraeve S, Hijar G, Zulantay I, Lucero RH, Velazquez E, Tellez T, Sanchez Leon Z, Galvao L, Nolder D, Monje Rumi M, Levi JE, Ramirez JD, Zorrilla P, Flores M, Jercic MI, Crisante G, Anez N, De Castro AM, Gonzalez CI, Acosta Viana K, Yachelini P, Torrico F, Robello C, Diosque P, Triana Chavez O, Aznar C, Russomando G, Buscher P, Assal A, Guhl F, Sosa Estani S, DaSilva A, Britto C, Luquetti A, Ladzins J. International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients. PLoS Negl Trop Dis. 2011 Jan 11;5(1):e931. doi: 10.1371/journal.pntd.0000931.

    PubMed 21264349

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Benznidazole in people with Chagas Disease, run by Instituto Nacional de Parasitologia Dr. Mario Fatala Chaben at 1 site in Argentina.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02386358, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in