Safety and Efficacy: IV Zanamivir vs Oral Oseltamivir in Severe Influenza
The study was nevertheless designed to determine whether 600 mg IV zanamivir resulted in an improved time to clinical response of 1.5 days or better.
Intravenous (IV) zanamivir was as safe and efficacious as oral oseltamivir when used in a population of patients with severe influenza, according to results of an international phase 3 trial published in Lancet Respiratory Medicine.
“We decided to take on the IV zanamivir trials, because we found ourselves in clinical circumstances [in which] we could not use either oral oseltamivir or inhaled zanamivir, the only options available at the time,” explained lead investigator Francisco Marty, MD, in an email interview with Infectious Disease Advisor. “Zanamivir provides the advantage of being able to treat influenza strains that are oseltamivir resistant.” Zanamivir, a neuraminidase inhibitor active against both influenza A and influenza B, has the same mechanism of action as oseltamivir. It is currently approved by the US Food and Drug Administration (FDA) in the prophylaxis and treatment of influenza in the form of an inhaled dry powder delivered by a diskhaler device.
The international, randomized, double-blind, double-dummy, phase 3 trial (ClinicalTrials.gov identifier: NCT01231620) took place at 97 study-site hospitals in 26 countries and enrolled 626 patients age 16 and older hospitalized with severe influenza. Patients were randomly assigned to receive 300 mg IV zanamivir, 600 mg IV zanamivir, or standard-of-care 75 mg oral oseltamivir twice a day for 5 to 10 days. The patients were followed for 28 days after treatment completion.
Although the study investigators did not expect IV zanamivir to prove superior to standard of care in the absence of oseltamivir-resistant strains, the study was nevertheless designed to determine whether 600 mg IV zanamivir resulted in an improved time to clinical response of 1.5 days or better. Due to a dearth of placebo-controlled studies of oseltamivir in adults and adolescents hospitalized with severe influenza, the FDA did not permit a noninferiority study.
Results showed that differences in median time to clinical response were not statistically significant between study arms. Patients who received 600 mg IV zanamivir had a median time to clinical response of 5.14 days vs 5.87 days in patients who received 300 mg IV zanamivir (difference of –0.73 days; 95% CI, –1.79 to 0.75; P =.25) and 5.63 days in patients who received oral oseltamivir (difference of –0.48 days; 95% CI, –2.11 to 0.97; P =.39). The rate of adverse events, most commonly diarrhea, respiratory failure, and constipation, was similar across all groups.
Dr Marty, an infectious disease specialist affiliated with the division of infectious diseases at Brigham and Women's Hospital in Boston, Massachusetts, told Infectious Disease Advisor that the robust clinical data generated in this international trial suggests that it would be beneficial to have IV zanamivir available as an additional option for influenza treatment. “The sicker patients who could not take orally administered drugs for any reason could not be randomized in this trial but are the ones who would need this drug the most. In case of a new pandemic — bird flu, for example — or if an oseltamivir-resistant outbreak or epidemic were to occur, having IV zanamivir approved and available would be of benefit to patients.”
Marty FM, Vidal-Puigserver J, Clark C, et al. Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial. Lancet Respir Med. 2017;5:135-146. doi:10.1016/S2213-2600(16)30435-0