Table 2.

Clinical Efficacy of Antivirals Currently Recommended by the Centers for Disease Control and Prevention for the Treatment of Influenza^a

Reference, year	Clinical setting	Trial description	No. of patients	Treatment	Primary end point	Primary outcomes
Polymerase acidic endonuclease inhibitor
Baloxavir
Hayden et al,48 2018	Uncomplicated influenza in healthy adults and adolescents	Phase 2 R, DB, PC	400	Baloxavir (single dose of 10, 20, or 40 mg) or placebo	Time to alleviation of symptoms	Median time to alleviation of symptoms was shorter in each of the baloxavir dose groups (54.2 h in the 10-mg group, 51.0 h in the 20-mg group, 49.5 h in the 40-mg group) than in the placebo group (77.7 h) (P=.009, P=.02, and P=.005, respectively)
CAPSTONE-1,48 2018	Uncomplicated influenza in healthy adults and adolescents	Phase 3 R, DB, PC, ACC	1436	Baloxavir (single dose of 40 mg for patients weighing <80 kg or 80 mg for those ≥80 kg) or oseltamivir (75 mg bid) or placebo	Time to alleviation of symptoms	Median time to alleviation of symptoms was shorter in the baloxavir group than in the placebo group in the ITT infected population (53.7 h vs 80.2 h; P<.001) and ITT population (65.4 h vs 88.6 h; P<.001) and similar to the oseltamivir group
Ison et al (CAPSTONE-2),49 2020	Uncomplicated influenza in high-risk adolescent and adult outpatients	Phase 3 R, DB, PC, ACC	2184	Baloxavir (single dose of 40 mg for patients weighing <80 kg or 80 mg for those ≥80 kg) or oseltamivir (75 mg bid) or placebo	Time to improvement of influenza symptoms	Time to improvement of symptoms was shorter in the baloxavir group than in the placebo group (73.2 h vs 102.3 h; P<.0001); this difference was significant in patients with influenza A, influenza B, asthma, or chronic lung disease. Time to improvement of symptoms was similar between baloxavir and oseltamivir in patients with influenza A but shorter in patients with influenza B (P=.025)
Baker et al (miniSTONE-2),50 2020	Acute influenza in children (1-12 y)	Phase 3 R, DB, ACC	176	Baloxavir (single dose based on weight; 2 mg/kg for those weighing <20 kg and a single dose of 40 mg for those weighing ≥20 kg) or oseltamivir (30 mg for patients weighing ≤15 kg, 45 mg for >15 to ≤23 kg, 60 mg for >23 to ≤40 kg, and 75 mg for >40 kg, bid)	Incidence, severity, and timing of AEs	The overall incidence of AEs was similar between the baloxavir group (46.1%) and the oseltamivir group (53.4%). The incidence of AEs related to study drug was low in both the baloxavir (2.6%) and oseltamivir (8.6%) groups
Ikematsu et al,51 2020	Prophylaxis against influenza in healthy household contacts	R, DB, PC	752	Single, weight-based oral dose of baloxavir or matching placebo. ≥12 y at screening: weight <80 kg, 40 mg; ≥80 kg, 80 mg <12 y at screening: weight <10 kg, 1 mg/kg; 10 to <20 kg, 10 mg; 20 to <40 kg, 20 mg; ≥40 kg, 40 mg	Laboratory-confirmed clinical influenza	Laboratory-confirmed clinical influenza was reduced in the baloxavir group compared with the placebo group (1.9% vs 13.6%, respectively; P<.001)
Neuraminidase inhibitors
Oseltamivir phosphate
Treanor et al,52 2000	Acute influenza in nonimmunized, previously healthy adults	R, DB, PC	629	Oseltamivir (75 mg or 150 mg bid) or placebo	Time to resolution of illness	Both dose levels of oseltamivir (71.5 h, P<.001 [75 mg]; 69.9 h, P<.006 [150 mg]) resulted in reductions in the duration of illness vs placebo (103.3 h)
Hayden et al,53 1999	Healthy adult volunteers susceptible to viral influenza challenge	R, DB, PC	117	Prophylaxis study: oseltamivir (100 mg bid or 100 mg qd) or placebo Treatment study: oseltamivir (20, 100, or 200 mg bid or 200 mg qd) or placebo	Frequency of viral shedding and infection	No oseltamivir recipients had recovery of challenge virus from nasal washings (100% efficacy vs 50% in the placebo group; P<.001). Median time to cessation of viral shedding was reduced from 107 h in the placebo group to 58 h in the combined oseltamivir group (P=.003)
Peramivir
Kohno et al,54 2010	Previously healthy adults with ILI within the previous 48 h	R, DB, PC	300	Intravenous peramivir (300 mg or 600 mg) or placebo	Time from start of treatment to recovery	Peramivir significantly reduced time to alleviation of symptoms (median 59.1 h, P<.0019 [300 mg]; 59.9 h, P<.009 [600 mg]) vs placebo (median 81.8 h)
De Jong et al,55 2014	Patients hospitalized with suspected influenza	Phase 3 R, DB, PC	405	Intravenous peramivir (10 mg/kg qd, up to 600 mg/d maximum) or placebo, added to institution’s SOC	Time to clinical resolution	Time to clinical resolution did not differ between peramivir-treated or SOC-only patients (42.5 vs 49.5 h)
Zanamivir
Monto et al,56 1999	Adults with ILIb	Phase 2/3 (pooled data) R, DB, PC	1133	Phase 2 studies: zanamivir (10 mg inhaled qid) vs placebo Phase 3 studies: zanamivir (10 mg inhaled bid) vs placebob	Time to alleviation of major influenza symptoms	Median time to alleviation of influenza symptoms was reduced from 6 d in the placebo group to 5 d in the zanamivir group (P<.001)
Hedrick et al,57 2000	Children between the ages of 5 and 12 y with ILI	R, DB, PC	471	Zanamivir (10 mg bid) or placebo	Time to alleviation of clinically significant symptoms of influenza	Zanamivir significantly shortened median time to alleviation of symptoms vs placebo by 24% (4.0 vs 5.25 d; P<.001)
LaForce et al,58 2007	Community-dwelling, high-risk adults and adolescents	R, DB, PC	3363	Zanamivir (10 mg qd) or placebo	Proportion of randomized patients in whom symptomatic influenza A or B developed during prophylaxis	4/1678 (0.2%) Zanamivir-treated individuals had development of symptomatic culture/serology–confirmed influenza vs 23/1685 (1.4%) placebo recipients (P<.001), with an 83% protective efficacy

^aACC, active comparator controlled; AE, adverse event; bid, twice daily; DB, double-blind; ILI, influenzalike illness; PC, placebo-controlled; qd, once daily; qid, 4 times daily; R, randomized; SOC, standard of care; ITT, intention-to-treat.

^bSee individual studies for full treatment information.