Table 1.
Summary of study design, inclusion/exclusion criteria and participants of studies of adjunctive passive immune therapy for influenza
| Reference | Study design | Country (no sites), y | Influenza type | Setting | No participants (exp: cont %) | Sex (male) | Age, y (median, IQR) | Major inclusion criteria | Study primary endpoint | Mortality definition | Mortality (control group) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Passive immune therapy | |||||||||||
| Hung et al29 | Prospective cohort | Hong Kong (7), 2009‐10 | Pandemic H1N1 | ICU | 93 (22:78) | 68.8% | Exp: 48 (37‐56); Cont: 54 (43‐62) | ≥18 y; deterioration despite antivirals | Not stated | In‐hospital | 54.8% |
| Hung et al25 | Placebo‐controlled RCT | Hong Kong (1), 2010‐11 | Pandemic H1N1 | ICU | 35 (49:51) | 55.9% | Exp: 43 (37‐56); Cont 41‐59) | ≥18 y; severe CAP; deterioration despite antivirals | Mortality | 21‐d mortality | 23.5% |
| Beigel et al28 | Open‐label RCT | US (29), 2011‐15 | Seasonal (A + B) | Hospital | 87 (48:52) | 48.0% | Exp: 50 (38‐66); Cont: 57 (39‐71) |
Hypoxia or tachypnoea. Exclusion: suspicion that main illness not due to flu |
Time to normalisation of patients’ respiratory status | In‐hospital | 11.1% |
| Davey et al 26 | Blinded, placebo‐controlled RCT | US, Thailand, UK, Spain + 5 others (33), 2013‐18 | Seasonal (A + B) | Hospital | 329 (51:49) | 45.5% | Exp: 55 (41‐68); Cont: 57 (48‐68) | Illness onset ≤7 d; New score ≥2 | Outcome at Day 7 (ordinal scale) | 7‐day mortality | 1.3% |
| Beigel et al27 | Blinded, placebo‐controlled RCT | US (30), 2015‐19 | Seasonal (A) | Hospital | 138 (66;34) | 51.4% | Exp: 58(47‐69); 63 (44‐69) | Illness onset ≤7 d; New score ≥3 | Outcome at Day 7 (ordinal scale) | 28‐day mortality | 4.3% |
| Macrolide | |||||||||||
| Martin‐Loeches et al30 | Prospective cohort | Spain (148), 2009‐11 | Pandemic H1N1 | ICU | 733 (26:74) | 60.0% | Exp: 44 ± 14.0; Cont: 46 ± 13.9 | ≥15 y; Primary viral pneumonia | Mortality | In ICU | 28.1% |
| Lee et al31 | Open‐label RCT | Hong Kong (3), 2013‐16 | Seasonal (A + B) | Hospital | 50 (50:50) | 62.0% | Exp: 54.7 ± 18.5; Cont: 58.6 ± 18.1a |
≥18yrs; symptoms of ARI ≤4 d. Exclusion: no renal, hepatic, cardiac failure |
Plasma cytokine/chemokine from Days 0 to 10 | in‐hospital | 0% |
| NSAID | |||||||||||
| Hung et al33 | Blinded, placebo‐controlled RCT | Hong Kong, 2014‐17 | Seasonal [A/H3N2] | Hospital | 120 (50:50) | 58.3% | Exp: 70 (58.3‐38.3); Cont: 73.5 (60.3‐81.8) | ≥18 y; symptoms of ILI ≤72 h; CrCl ≥ 30 mL/min; no CHF | Mortality | 28‐day mortality | 26.7% |
| NSAID and macrolide | |||||||||||
| Hung et al32 | Open‐label RCT | Hong Kong (1), 2015 | Seasonal [A/H3N2] | Hospital | 217 (49:51) | 53.5% | Exp: 80 (72‐85); Cont: 81.5 (71‐87.3) | ≥18 y; symptoms ≤72 h; infiltrate on CXR | Mortality | 30‐day mortality | 8.2% |
| mTOR inhibitors | |||||||||||
| Wang et al34 | Open‐label RCT | Taiwan (1), 2009‐11 | Pandemic H1N1 | ICU | 38 (50:50) | 78.9% | Exp: 46.7 ± 12.1; Cont: 51.5 ± 16.0 a | ≥18 y; severe respiratory failure; ventilatory support | Not stated | In ICU | 42.1% |
| Statin | |||||||||||
| Chase et aln | Blinded, placebo‐controlled RCT | US (1), 2013‐18 | Seasonal (A + B) | Hospital | 116 (51:49) | 37.9% | Exp: 34 (23‐51); Cont: 43 (29‐58) | ≥18 y; prior statin therapy; liver cirrhosis/dysfunction | Change in Il‐6 after 72 h | In‐hospital | 0% |
Abbreviations: APACHE II, Acute Physiology, Age Chronic Health Evaluation II; ARI: Acute respiratory tract infection; CAP: community‐acquired pneumonia; CHF: congestive heart failure; COPD: chronic obstructive pulmonary disease; CrCl: creatinine clearance; CXR: chest radiograph; ICU: intensive care unit; ILI: influenza‐like illness; IQR: interquartile range; NEW: National Early Warning; NSAID: non‐steroidal anti‐inflammatory drug; RCT: randomised controlled trial.
Mean ± standard deviation.