Clinical Studies Of Zanamivir On Patients With Influenza Infection

Objective1. To evaluate the efficacy and safety of inhalation zanamivir on influenza (flu) and flu-like Chinese patients.2. To measure serum levels of proinflammatory cytokines in adult patients with seasonalinfluenza infection to explore the cytokine responses and determine whether there arespecific predictors associated with severity of seasonal influenza.MethodsPart1A multicenter, double-blind, and randomized controlled trial of inhalationzanamivir in influenzaA multicenter, double-blind, and randomized controlled trial was performed in286patients with flu-like symptoms. Patients were randomized to2groups received inhalationzanamivir10mg or placebo, bid, for5days respectively. In addition, the two groups weregiven supportive treatment. Assessments included oral temperature, stuffy nose, sore throat,cough, myalgia, headache and malaise. Laboratory testing and physical examination wereconducted on day6and day21and the vital signs and adverse events were recorded toassess the safety.Part2Clinical aspects and cytokine response in adults with seasonal influenzainfectionSeventy-two outpatients for laboratory-confirmed seasonal influenza infection werestudied: twenty-four seasonal influenza A patients and forty-eight seasonal influenza Bpatients. Thirty healthy volunteers were enrolled as a control group. Serum samples frominfluenza patients obtained on the admission day and6days later were measured for eightcytokines using enzyme-linked immunosorbent assay (ELISA). The clinical variables wererecorded prospectively.Results1. The remission time of flu-like patients in zanamivir group was84h, which wassignificantly shorter than that in placebo group (P<0.05).2.60h and72h after beginning treatment, the disease remission rate in zanamivir groupwas37.59%and44.68%, which were significantly higher than that in placebo group(P<0.05). 3. Among those patients with laboratory-confirmed influenza infection, the remissiontime in zanamivir group was also significantly shorter than that in placebo group(P<0.05).4. The incidence of adverse reactions was23.94%and22.22%in zanamivir group andplacebo group, respectively. There was no significant difference between the twogroups (P>0.05).5. Both in seasonal influenza A and B patients, the levels of IL-6, IL-33, TNF-α, IFN-γand IP-10were significantly higher than those in the control group. Furthermore, IL-17A, IL-29, IFN-γ and IP-10were increased in seasonal influenza B patients whencomparing with those in the seasonal influenza A patients.6. A negative correlation of IFN-γ and IP-10levels with lymphocyte count (r=-0.39,P=0.013; r=-0.44, P=0.005) were found in seasonal influenza infection.Conclusions1. Inhalation zanamivir is effective and safe for treating Chinese flu and flu-like patients.2. While a hyperactivated proinflammatory cytokine responses were found in seasonalinfluenza infection, a higher elevation of cytokines (IL-17A, IFN-γ and IP-10) ofadaptive-immunity were found in seasonal influenza B infection versus influenza A.3. IFN-γ and IP-10were important hallmarks in seasonal influenza infection, which canhelp clinicians make timely treatment decision for severe patients.