Chronic Chagas disease Infections and Infestations Chagas disease
Conditions
Interventions
In the first stage, baseline parasitaemia will be quantitated twice weekly over the course of one month to characterize the natural variation in T. cruzi blood stage densities for individuals at a qua
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult volunteers with chronic T. cruzi infection, a blood-stage parasite density of at least 2 parasite equivalents per mL, with or without end-organ involvement and: 1.1. Participant is willing and able to give informed consent for participation in the study. 1.2. Adult patients, male or female, aged over 18 years and less than 99 years. 1.3. Lives in the Belo Horizonte metropolitan area and can comply with study procedures. 1.4. Circulating parasitaemia greater or equal to 2 parasites equivalent per mL.
Exclusion criteria
Exclusion criteria: 1. Has received prior treatment with benznidazole, nifurtimox or posaconazole (either completely or incompletely). 2. History of hypersensitivity, allergic, or serious adverse reactions to any nitroimidazole compound, posaconazole and/or its components. 3. Inability to attend follow-up visits on the stipulated dates. 4. Acute or chronic health problems that, in the opinion of the principal investigator, may interfere with study completion. 5. Alcohol or drug dependence. 6. HIV infection or is immunocompromised. 7. Pregnant or breastfeeding. 8. Patients taking any immunosuppressant drugs. 9. QT prolongation (>450 ms for males; >470 ms for females). 10. Basic laboratory parameters outside the normal range or that are considered clinically relevant by the physician responsible for the patient. 10.1. Total white blood cell counts outside the normal range, as defined by an acceptable margin of +/- 5% (3,800 - 10,500 / mm3); 10.2. Transaminases (ALT and AST) outside the normal range, as defined by 25% above the upper limit of normal (ULN, > 1.25 x ULN). 11. Therapy with drugs metabolized by CYP3A4, such as terfenadine, astemizole, pimozide, halofantrine or quinidine, and HMG-CoA reductase inhibitors (simvastatin, lovastatin, and atorvastatin). 12. Patients receiving treatment with proton pump inhibitors or H2 receptor antagonists, phenytoin, efavirenz, and rifabutin, or who cannot discontinue it during the study period. 13. Patients receiving any drugs known to prolong the QT interval significantly.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stage 1: Wavelength and amplitude of the temporal fluctuations in the blood-stage parasite density estimated from twice weekly blood-stage parasite densities taken over one month Stage 2: Parasite clearance half-life in blood using serial qPCR after sub-curative drug regimens Stage 3: Assessment of tissue-stage load measured by time to recrudescent parasite density detectable by qPCR | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to reach new steady-state parasite density measured using qPCR from the time of the dose with suboptimal treatment until up to 12 weeks 2. Fold-change in parasite density between estimated baseline steady-state and recrudescent steady state | — |
Countries
Brazil
Outcome results
None listed