Chagas Disease on chronic phase MedDRA version: 19.0 Level: LLT Classification code 10008384 Term: Chagas' disease System Organ Class: 100000004862
Conditions
Interventions
Product Name: Benznidazol
Pharmaceutical Form: Tablet
INN or Proposed INN: BENZNIDAZOLE
CAS Number: 22994-85-0
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 150-4
Sponsors
Fundación Hospital Universitari Vall d'Hebron - Institut de Recerca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients = 18 years old - Patients diagnosed of Chagas disease through 2 positive serologic tests, using different antigens. - Detectable DNA of T.Cruzi in peripheral blood through PCR. - Written Informed Consent - Weight = 50 kg to =80 kg - Patients capable to fulfill with the protocol visits and procedures and have a permanent address - Patients must be residents of Free Areas transmission vector (Triatoma infestans). (Defined by local health programs or under the definition of PAHO / WHO - Childbearing Woman with a negative pregnancy test in serum or urine at baseline. During the treatment phase, breastfeeding is not allow and a barrier contraceptive method has to be used. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Patients treated previously with benznidazol o nifurtimox (complete or incomplete) - Inability to do the Follow Up at the stipulated dates - Acute or chronic health problems, that according to PI opinion can interfere in the efficacy and/or safety drug evaluation (exemple: acute infections, HIV infection, hepatic disease with liver function affected and renal disease that needs supportive treatment) - Precedent of alcohol abuse - Patients with Known hypersensibility to nitroimidazols, for example metronidazol - Any concomitant use or a history of use of allopurinol, antimicrobial or anti-parasitic agents or antifungal - Laboratory parameters out of range o clinically relevant according to investigator criteria: o Leukocytes must be within the normal range, with an acceptable margin of +/- 5% o Platelets must be within the normal range up to 550,000 / mm3 or 550x109 / L o Total bilirubin must be within the normal range o Transaminases (ALT and AST) should be within the normal range, with an acceptable margin of 25% above the upper limit of normal (ULN) <1.25 x ULN. o Creatinine should be within the normal range, with an acceptable margin of 10% above the ULN, <1.10 x ULN. o Alkaline phosphatase must be within the normal range until CTCAE Grade 1 (<2.5 x ULN) o GGT should be within the normal range up to 2x ULN. o Fasting glucose should be within the normal range
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effectiveness of different regimens of benznidazole by the proportion of patients with sustained suppression of the parasitic load measured by PCR in peripheral blood during the first 12 months of follow up after the start of treatment in patients older than 18 years with Chagas disease in chronic phase in both its indeterminate or organic form (digestive or heart ) .;Secondary Objective: - Assess for different regimes, the parasitic kinetic at week 1,2,4 and 8 of treatment and 4,6,8 and 12 months after starting treatment in patients over 18 with chronic phase Chagas both its indeterminate form and organic ( gastrointestinal or cardiac ) -Evaluate for different regimes, the serologic response in chronic phase indeterminate form both in symptomatic and by trend curves OD by ELISA methods -Assess tolerability and safety of different regimens of benznidazole for Chagas disease in chronic phase, in form with or without apparent pathology ( digestive or heart ) - Correlate Benznidazol blood levels in the equilibrium phase with the therapeutic response and adverse effects. - Correlate the presence of HLA B3505 with serious side effects - Correlate different DTUs parasites and geographical origins with therapeutic response;Primary end point(s): Efficacy: Parasitological response determined by the presence of parasite DNA in peripheral blood measured by PCR and interpreted qualitatively during the treatment and follow-up. Treatment times and are defined by monitoring the different treatment arms. Safety: - Incidence and severity of the side effects - Treatment interruption;Timepoint(s) of evaluation of this end point: 15 or 60 days depending on the treatment arm | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Negativization maintained during the treatment phase and the first 12 months of follow up. • Proportion of patients with positive PCR in each of the points of analysis. • Changes in the parasite load in the different points of analysis measured by detecting parasite DNA in peripheral blood by quantitative PCR • Evolution of the serological response comparing baseline results with the end of follow-up results. • Range of biomarker levels decreased at 6 and 12 months follow-up on the screening visit • Proportion of patients achieving marker levels decrease below the threshold of positivity (previously defined).;Timepoint(s) of evaluation of this end point: - During treatment phase and 12 months after treatment - Different time point. - Different time point - At the end of follow up - 6 and 12 months follow-up period - Different time point | — |
Countries
Argentina, Brazil, Colombia, Spain
Contacts
Public ContactPROSICS
Fundación Hospital Universitari Vall d'Hebron - Institut de Recerca
Outcome results
None listed