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DISULFIRAM REPURPOSING IN THE COMBINED CHEMOTHERAPY OF CHAGAS DISEASE A PROTOCOL FOR PHASE I/II CLINICAL TRIAL
Quimioterapia
Disulfiram
Reaproveitamento de drogas
Protocolo
Ensaio clínico de fase I / II
Author
Affilliation
Abstract
Background: Chagas disease (CD) has high morbimortality and the available trypanocidal treatment, including benznidazole (BZ),
has limited efficacy in chronic patients. Furthermore, BZ causes adverse effects (AE) that prevent treatment completion in up to 30%
of patients. The use of repositioned drugs or drug combination may provide an effective trypanocidal treatment. Disulfiram (DF) may
enhance BZ activity and decrease BZ related AE. This study aims to assess the safety of a new combination of drugs for CD therapy,
assuming BZ as the drug of choice plus DF as repositioned drug.
Methods: This single-centre, open-label, phase I/II clinical trial was designed to evaluate the safety of the combined use of BZ plus
DF for CD therapy. Participants are adults with indeterminate form of chronic CD, both sexes, aged from 18 to 70 years old and
Trypanosoma cruzi polymerase chain reaction-positive. The primary outcome will be the occurrence of serious AE. The secondary
outcome will be post-treatment Trypanosoma cruzi polymerase chain reaction negativization. Six groups of 9 patients will be
sequentially tested. The first group will be allocated to receive BZ 100mg/d + DF 250mg/d for 60 days. Upon safety confirmation
(<1/3 of participants with serious AE), the combination dose will be gradually increased and dispensed to 5 groups (group II:BZ
200mg/day+DF 250mg/d; group III:BZ 300mg/d + DF 250mg/d; group IV:BZ 100mg/d + DF 500mg/d; group V:BZ 200mg/d + DF
500mg/d; group VI: BZ 300mg/d + DF 500mg/d) for 60 days in order to determine the maximum tolerated dose.
Discussion: Our hypothesis is that the drug combination will be well tolerated and allow the proposal of phase II trials in larger scale
to test the efficacy of the new drug combination in CD. We expect that the studied combination will have less AEs with an efficacy.
Keywords in Portuguese
Doença de ChagasQuimioterapia
Disulfiram
Reaproveitamento de drogas
Protocolo
Ensaio clínico de fase I / II
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