دورية أكاديمية
أعرض في EDS

Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial.

التفاصيل البيبلوغرافية
العنوان: Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial.
المؤلفون: Pinazo MJ; Barcelona Institute for Global Health, ISGlobal-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Spain. Electronic address: mpinazo@dndi.org., Forsyth C; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil., Losada I; Barcelona Institute for Global Health, ISGlobal-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain., Esteban ET; Unidad de Patología Importada y Salud Internacional. Hospital Universitario La Paz, Madrid, Spain., García-Rodríguez M; Infectious Diseases Service, International Health Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain., Villegas ML; Department of Internal Medicine, Hospital General de L'Hospitalet, Complex Hospitalari Universitari Moisès Broggi, Barcelona, Spain., Molina I; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Spain; Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Barcelona, Spain., Crespillo-Andújar C; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Spain; Unidad de Patología Importada y Salud Internacional. Hospital Universitario La Paz, Madrid, Spain; National Referral Unit for Tropical Diseases, Infectious Diseases Department, Ramón y Cajal University Hospital, IRYCIS, Madrid, Spain., Gállego M; Barcelona Institute for Global Health, ISGlobal-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Spain; Parasitology Section, Department of Biology, Health, and Environment, Faculty of Pharmacy and Food Science, Universitat de Barcelona, Barcelona, Spain., Ballart C; Barcelona Institute for Global Health, ISGlobal-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Parasitology Section, Department of Biology, Health, and Environment, Faculty of Pharmacy and Food Science, Universitat de Barcelona, Barcelona, Spain., Ramirez JC; Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas, CONICET-GCBA, Buenos Aires, Argentina., Aden T; Institute of Medical Microbiology, Immunology, and Parasitology, University Hospital Bonn, Germany., Hoerauf A; Institute of Medical Microbiology, Immunology, and Parasitology, University Hospital Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany., Pfarr K; Institute of Medical Microbiology, Immunology, and Parasitology, University Hospital Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany., Vaillant M; Competence Centre for Methodology and Statistics, Luxembourg Institute of Health, Strassen, Luxembourg., Marques T; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil., Fernandes J; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil., Blum B; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil., Ribeiro I; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil., Sosa-Estani S; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil; Centro de Investigaciones en Epidemiología y Salud Pública (CIESP-CONICET), Buenos Aires, Argentina., Barreira F; Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil., Gascón J; Barcelona Institute for Global Health, ISGlobal-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Spain.
مؤلفون مشاركون: FEXI-12 Study Team
المصدر: The Lancet. Infectious diseases [Lancet Infect Dis] 2024 Apr; Vol. 24 (4), pp. 395-403. Date of Electronic Publication: 2024 Jan 11.
نوع المنشور: Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase II; Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-4457 (Electronic) Linking ISSN: 14733099 NLM ISO Abbreviation: Lancet Infect Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001-
مواضيع طبية MeSH: Chagas Disease*/drug therapy , Trypanosoma cruzi* , Nitroimidazoles*, Adult ; Humans ; Adolescent ; Young Adult ; Middle Aged ; Treatment Outcome ; Nifurtimox/adverse effects ; Double-Blind Method
مستخلص: Background: More than six million people worldwide, particularly in vulnerable communities in Latin America, are infected with Trypanosoma cruzi, the causative agent of Chagas disease. Only a small portion have access to diagnosis and treatment. Both drugs used to treat this chronic, neglected infection, benznidazole and nifurtimox, were developed more than 50 years ago, and adverse drug reactions during treatment pose a major barrier, causing 20% of patients to discontinue therapy. Fexinidazole proved efficacious in an earlier, interrupted clinical trial, but the doses evaluated were not well tolerated. The present study evaluated fexinidazole at lower doses and for shorter treatment durations.
Methods: In this randomised, double-blind, phase 2 trial, we included adult patients (18-60 years old) with confirmed T cruzi infection by serology and PCR and without signs of organ involvement. We evaluated three regimens of fexinidazole-600 mg once daily for 10 days (6·0 g total dose), 1200 mg daily for 3 days (3·6 g), and 600 mg daily for 3 days followed by 1200 mg daily for 4 days (6·6 g)-and compared them with a historical placebo control group (n=47). The primary endpoint was sustained negative results by PCR at end of treatment and on each visit up to four months of follow-up. This study is registered with ClinicalTrials.gov, NCT03587766, and EudraCT, 2016-004905-15.
Findings: Between Oct 16, 2017, and Aug 7, 2018, we enrolled 45 patients (n=15 for each group), of whom 43 completed the study. Eight (19%) of 43 fexinidazole-treated patients reached the primary endpoint, compared with six (13%) of 46 in the historical control group. Mean parasite load decreased sharply following treatment but rebounded beginning 10 weeks after treatment. Five participants had seven grade 3 adverse events: carpal tunnel, sciatica, device infection, pneumonia, staphylococcal infection, and joint and device dislocation. Two participants discontinued treatment due to adverse events unrelated to fexinidazole.
Interpretation: The fexinidazole regimens in this study had an acceptable safety profile but did not prove effective against T cruzi infection. Development of fexinidazole monotherapy for treating T cruzi infection has been stopped.
Funding: The Drugs for Neglected Diseases initiative.
Competing Interests: Declaration of interests AH reports being Chair of the German Network against Neglected Tropical Diseases, a German advocacy group to fight neglected tropical diseases. All other authors declare no competing interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
سلسلة جزيئية: ClinicalTrials.gov NCT03587766
المشرفين على المادة: 306ERL82IR (fexinidazole)
M84I3K7C2O (Nifurtimox)
0 (Nitroimidazoles)
تواريخ الأحداث: Date Created: 20240113 Date Completed: 20240325 Latest Revision: 20240325
رمز التحديث: 20240325
DOI: 10.1016/S1473-3099(23)00651-5
PMID: 38218194
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-4457
DOI:10.1016/S1473-3099(23)00651-5