Study Shows Promise for Intravenous Zanamivir for Hospitalized Patients With Flu

Intravenous zanamivir (IVZ) could be a good option for the treatment of influenza in oseltamivir-resistant patients and in those unable to digest medication, according to a phase 3 trial.

IVZ at 600 mg twice daily or 300 mg twice daily had comparable efficacy to oral oseltamivir (OS) 75 mg twice daily for patients hospitalized with severe influenza in terms of time to resolution of the disease and overall mortality, according to a new phase 3 trial.
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“This has been the largest influenza study ever done in sicker patients with influenza,” said lead study author Francisco Marty, MD, an infectious disease specialist and physician at Brigham and Women’s Hospital in Boston, noting they saw no signal of increased toxicity with IVZ compared with OS.

Researchers randomly assigned hospitalized patients with suspected or confirmed influenza within 6 days of illness onset to receive 600 mg IVZ, 300 mg IVZ, or 75 mg OS twice-daily for 5-10 days and followed them for 28 days. They defined clinical response  as resolution of fever and hypoxia and normalization of ≥ 2 of 3 parameters (respiratory rate or mechanical ventilation status, heart rate, blood pressure) or hospital discharge—whichever occurred first. Primary endpoint was time to clinical response (TTCR) in the influenza positive population (IPP), powered to demonstrate superiority of ≥ 1.5 days between 600 mg IVZ vs. OS or between IVZ arms.

Investigators enrolled 626 subjects from January 2011-March 2015. In IPP, 16% were mechanically ventilated and 39% were in the ICU at baseline. Influenza viruses included A/H3N2 (45%), H1N1 (38%), untyped A (1%), B (14%), and co-infection (2%). TTCR was not significantly different for pair-wise comparisons in the IPP or in the ICU subgroup.

The proportion of subjects who achieved a clinical response was higher in the IVZ arms. Adverse events (most commonly diarrhea, constipation, and increased alanine aminotransferase) and serious adverse events were reported in 61% and 18% subjects, respectively; they found nature and frequency to be similar across all arms. Mortality was 7% in each of the IVZ arms and 5% in the OS arm, with the most common causes of death respiratory failure and septic shock.

“The expected use of IV zanamivir would be for sicker patients who require hospitalization or intensive care unit care and cannot take oral or inhaled approved antivirals, so it would not affect primary care daily outpatient practices,” Dr Marty said. “But it would be a good option to have available for patients who develop oseltamivir-resistant influenza as IV zanamivir is active against these viruses and for any of their patients who were to develop severe influenza and could not take oral or inhaled antivirals.”

Future research will depend on the Food and Drug Administration’s final review on the study results, he said.

—Mike Bederka

Reference:

Marty F, Puigserver JV, Clark C, et al. IV zanamivir (IVZ) compared with oral oseltamivir (OS) to treat influenza in hospitalized adults and adolescents: a randomized, double-blind, double-dummy phase III trial (NAI114373). Options for the Control of Influenza 2016 Conference, Chicago. Aug. 27, 2016.