Browsing by Autor "Fabiana Barreira"

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A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease
(Oxford University Press, 2022) Faustino Torrico; Joaquím Gascón; Lourdes Ortiz; Jimy Pinto; Gimena Rojas; Alejandro Palacios; Fabiana Barreira; Bethania Blum; Alejandro G. Schijman; Michel Vaillant
NCT02498782.
Benznidazole in Chagas disease study: do the data justify progression to phase 3? – Authors’ reply
(Elsevier BV, 2021) Faustino Torrico; Fabiana Barreira; Nathalie Strub‐Wourgaft; Isabella Ribeiro; Sergio Sosa‐Estáni
Direct evidence gap on fixed versus adjusted‐dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta‐analysis
(Wiley, 2022) Agustín Ciapponi; Fabiana Barreira; Lucas Perelli; Ariel Bardach; Joaquím Gascón; Israel Molina; Carlos A. Morillo; Nilda Graciela Prado; Adelina Riarte; Faustino Torrico
The study protocol was registered in PROSPERO (CRD42019120905).
Fixed vs adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: A systematic review and meta-analysis
(Public Library of Science, 2020) Agustín Ciapponi; Fabiana Barreira; Lucas Perelli; Ariel Bardach; Joaquím Gascón; Israel Molina; Carlos A. Morillo; Nilda Graciela Prado; Adelina Riarte; Faustino Torrico
Chagas disease is a neglected disease that remains a public health threat, particularly in Latin America. The most important treatment options are nitroimidazole derivatives, such as nifurtimox and benznidazole (BZN). Some studies suggest that for adults seropositive to T. cruzi but without clinically evident chronic Chagas cardiomyopathy (CCC), a simple fixed-dose scheme of BZN could be equivalent to a weight-adjusted dose. We compared the efficacy and safety of a fixed dose of BZN with an adjusted dose for T. cruzi seropositive adults without CCC. We used the Cochrane methods, and reported according to the PRISMA statement. We included randomized controlled trials (RCTs) allocating participants to fixed and/or adjusted doses of BZN for T. cruzi seropositive adults without CCC. We searched (December 2019) Cochrane, MEDLINE, EMBASE, LILACS, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP), and contacted Chagas experts. Selection, data extraction, and risk of bias assessment, using the Cochrane tool, were performed independently by pairs of reviewers. Discrepancies were solved by consensus within the team. Primary outcomes were parasite-related outcomes and efficacy or patient-related safety outcomes. We conducted a meta-analysis using RevMan 5.3 software and used GRADE summary of finding tables to present the certainty of evidence by outcome. We identified 655 records through our search strategy and 10 studies (four of them ongoing) met our inclusion criteria. We did not find any study directly comparing fixed vs adjusted doses of BZN, however, some outcomes allowed subgroup comparisons between fixed and adjusted doses of BZN against placebo. Moderate-certainty evidence suggests no important subgroup differences for positive PCR at one year and for three safety outcomes (drug discontinuation, peripheral neuropathy, and mild rash). The same effect was observed for any serious adverse events (low-certainty evidence). All subgroups showed similar effects (I2 0% for all these subgroup comparisons but 32% for peripheral neuropathy), supporting the equivalence of BZN schemes. We conclude that there is no direct evidence comparing fixed and adjusted doses of BZN. Based on low to very low certainty of evidence for critical clinical outcomes and moderate certainty of evidence for important outcomes, fixed and adjusted doses may be equivalent in terms of safety and efficacy. An individual patient data network meta-analysis could better address this issue.
New regimens of benznidazole for the treatment of chronic Chagas disease in adult participants in indeterminate form or with mild cardiac progression (NuestroBen study): protocol for a phase III randomised, multicentre non-inferiority clinical trial
(BMJ, 2025) Tayná Marques; Colin Forsyth; Fabiana Barreira; Carola Lombas; B Oliveira; Mónica Laserna; Israel Molina; María del Carmen Bangher; Rosa Martí Fernández; Susana Lloveras
NCT04897516.
New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial
(Elsevier BV, 2021) Faustino Torrico; Joaquím Gascón; Fabiana Barreira; Bethania Blum; Igor C. Almeida; Cristina Alonso‐Vega; Tayná Barboza; Graeme Bilbe; Erika Correia; Wilson García
For the Spanish translation of the abstract see Supplementary Materials section.
Quantifying anti-trypanosomal treatment effects in chronic indeterminate Chagas disease: an individual patient data meta-analysis of two proof of concept trials
(2024) James A Watson; Cintia Cruz; Fabiana Barreira; C. Forsyth; Alejandro G. Schijman; Rhys Peploe; Frauke Assmus; Caitlin Naylor; Jennifer Lee; Somya Mehra
Abstract Background The current antiparasitic treatment for chronic Chagas disease of 8 weeks daily benznidazole or nifurtimox is poorly tolerated and reaches only a small minority of those with chronic infections. Defining parasitological cure is compromised by the low blood trypomastigote densities, which fluctuate close to or below the limit of qPCR detection. Methods To address this limitation and improve the assessment of parasitological cure we developed a probabilistic model of therapeutic efficacy based on serial qPCR data. We pooled clinical and laboratory data from two prospective trials in Bolivian adults with chronic indeterminate Chagas disease. In both trials randomised arms included placebo or standard of care benznida-zole (300mg/day for 8 weeks). In the first trial, the experimental arms were fosravuconazole monotherapies (400mg/week for 4 or 8 weeks, or 200mg/week for 8 weeks); in the second trial the experimental arms were shorter or lower dose benznidazole regimens (300mg/day for 2 or 4, or 150mg/day for 4 weeks), or combinations of fosravuconazole 300mg weekly for 8 weeks with either benznidazole 150mg/day for 4 weeks or benznidazole 300mg/week for 8 weeks. Serial parasite densities were estimated from triplicate qPCRs targeting T. cruzi satellite DNA taken from one to three 5 or 10ml blood samples at 8-12 visits over one year. Treatment efficacies were estimated under a hierarchical Bayesian model, taking as input serial cycle threshold (Ct) data grouped by time point, blood draw and technical replicate. The primary analysis was done in a per-protocol population defined as patients randomised to placebo or patients who took an active treatment >80% of the allocated treatment duration. Results The two trials randomised 441 patients. 34,804 qPCR Ct values were recorded over 5,402 unique visits, comprising 449 participant years follow-up. In a per-protocol population ( n =424), an estimated 81% (95% Credible Interval [CrI] 70 to 89%, n =69) had parasitological cure following benznidazole 300mg/day for 8 weeks. All other benznidazole regimens had similar estimated cure proportions (95% CrIs >63%) except the 2-week regimen (63% cured [95%CrI 43-81%], n =27, probability of inferiority relative 8-week: 0.95). Recurrent parasitaemias following benznidazole were at substantially lower densities than at baseline. In comparison, only 3.9% of patients allocated to placebo were cured (95%CrI 1 to 9%, n =77). Fosravuconazole was relatively ineffective: 23% cured following 400mg for 8 weeks (95%CrI, 10 to 40%, n =45); 9% following 400mg for 4 weeks (95%CrI 3 to 21%, n =46); and 2% following 200mg for 8 weeks (95%CrI 0 to 11%, n =48). Recurrent parasitaemias one year after fosravuconazole treatment were only slightly lower than at baseline. Fosravuconazole caused dose-dependent increases in liver transaminases. Conclusions Therapeutic assessments in Chagas disease must account probabilistically for qPCR test performance and low density post treatment parasitaemias. In Bolivian chronic Chagas disease, weekly dosing for eight weeks or daily dosing over four weeks both appear as effective as the current eight weeks daily regimen. The total dose of benznidazole in the current standard of care regimen is excessive.