Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial

Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference

“…Influenza is seasonal, meaning that for each season enrollment per clinical site is limited to approximately six weeks, with peak activity covering only two weeks on average. Additionally, more than one third of hospital clinical sites do not enroll a single patient and another quarter enroll only one or two subjects (Beigel et al, 2017;de Jong et al, 2014;Marty et al, 2017). To facilitate adequate enrollment, a large number of sites across the globe are required to complete the study in a timely manner.…”

Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference

“…The Phase III studies were carried out at 160 sites in 26 countries. Patients were enrolled within 6 days of symptom onset, and received 300 IVZ or 600 IVZ BID or oseltamivir (OS) 75 mg BID for 5-10 days (Marty et al, 2017). Time to clinical response, a composite of vital sign resolution and hospital discharge was the primary endpoint.…”

“…797 NA sequences from 379 Phase III subjects identified 21 resistance substitutions in 50 subjects (11 in H1N1pdm09; 36 in H3N2; 3 in B viruses), most were present at day 1, thus were not selected during treatment. Five had H275Y NA substitution, four of whom were in the oseltamivir arm, and the fifth although in the IVZ arm, had prior OS treatment (Marty et al, 2017). Four treatment-associated NAI-resistant substitutions were identified in viruses that could not be cultured: two in OS, R292R/K (day 7) and D198D/G (day 3) and two in 300IVZ, N294S/N (day 2) and T325I (day 2) (Marty et al, 2017).…”

“…Five had H275Y NA substitution, four of whom were in the oseltamivir arm, and the fifth although in the IVZ arm, had prior OS treatment (Marty et al, 2017). Four treatment-associated NAI-resistant substitutions were identified in viruses that could not be cultured: two in OS, R292R/K (day 7) and D198D/G (day 3) and two in 300IVZ, N294S/N (day 2) and T325I (day 2) (Marty et al, 2017). No novel zanamivir resistance substitutions were detected from the clinical studies evaluating IV zanamivir in severe influenza.…”

“…Clinical endpoints can include time to resolution of fever, or time to normalization of vital signs such as respiratory or heart rate, blood pressure, oxygen saturation, or mortality. Endpoints in hospitalized patients are problematic due to the heterogeneity of clinical backgrounds and disease severities at admission, (de Jong et al, 2014;Marty et al, 2017). Other endpoints can include patient reported outcomes, such as the FluiiQ™ questionnaire (Osborne et al, 2011), or the Flu-Pro © survey (Powers et al, 2016).…”