Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial.
Abstract | BACKGROUND: METHODS: We did a randomised, prospective, double-blind, double-dummy, controlled trial comparing posaconazole (intravenous or oral posaconazole 300 mg twice on day 1, followed by 300 mg once a day for days 2-84) with voriconazole (6 mg/kg intravenous or 300 mg oral twice on day 1 followed by 4 mg/kg intravenously or 200 mg orally twice a day for days 2-84) for 12 weeks or less in the primary treatment of invasive aspergillosis. Participants were from 91 study sites in 26 countries, were aged 13 years or older, weighed at least 40 kg, and met criteria for proven, probable, or possible fungal disease. Participants were randomly assigned (1:1) via a computer-generated randomisation schedule with stratification by risk status. The primary endpoint was cumulative all-cause mortality up until day 42 in the intention-to-treat (ITT) population (defined as randomly assigned participants who received ≥1 dose of study drug), with a 10% non-inferiority margin. The ITT population was also evaluated for safety. This study is registered with ClinicalTrials.gov, NCT01782131, and EudraCT, 2011-003938-14. FINDINGS: Between Oct 25, 2013, and Sept 10, 2019, of 653 individuals assessed for eligibility, 575 ITT participants were randomly assigned and received one or more doses of study drug (n=288 [50%] posaconazole, n=287 [50%] voriconazole). Mortality up until day 42 was 15% (44 of 288) in the posaconazole group and 21% (59 of 287) in the voriconazole group (treatment difference -5·3% [95% CI -11·6 to 1·0]; p<0·0001). Mortality up until day 42 in the full-analysis-set subpopulation (ITT participants with proven or probable invasive aspergillosis) supported this conclusion: 31 (19%) of 163 participants in the posaconazole group and 32 (19%) of 171 participants in the voriconazole group (treatment difference 0·3% [95% CI -8·2 to 8·8]). The most frequently reported treatment-related adverse events (incidence >3%) were increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT), nausea, hypokalaemia, and vomiting in the posaconazole group and increased ALT, AST, or alkaline phosphatase, hallucination, increased γ-glutamyltransferase peptidase, nausea, and blurred vision in the voriconazole group. The overall incidence of treatment-related adverse event rates in the ITT population was 30% for posaconazole and 40% for voriconazole (treatment difference -10·2% [95% CI -17·9 to -2·4]). INTERPRETATION: FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.
|
Authors | Johan A Maertens, Galia Rahav, Dong-Gun Lee, Alfredo Ponce-de-León, Isabel Cristina Ramírez Sánchez, Nikolay Klimko, Anne Sonet, Shariq Haider, Juan Diego Vélez, Issam Raad, Liang-Piu Koh, Meinolf Karthaus, Jianying Zhou, Ronen Ben-Ami, Mary R Motyl, Seongah Han, Anjana Grandhi, Hetty Waskin, study investigators |
Journal | Lancet (London, England)
(Lancet)
Vol. 397
Issue 10273
Pg. 499-509
(02 06 2021)
ISSN: 1474-547X [Electronic] England |
PMID | 33549194
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2021 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antifungal Agents
- Triazoles
- posaconazole
- Voriconazole
|
Topics |
- Administration, Intravenous
- Administration, Oral
- Adolescent
- Adult
- Antifungal Agents
(administration & dosage, adverse effects)
- Double-Blind Method
- Female
- Humans
- Invasive Pulmonary Aspergillosis
(drug therapy, mortality)
- Male
- Middle Aged
- Prospective Studies
- Triazoles
(administration & dosage, adverse effects)
- Voriconazole
(administration & dosage, adverse effects)
- Young Adult
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|