Table 3.
Four RCTs conducted in adults (≥18 years old)
| Author, year |
Study period and countr(ies) | Treatment arms Brand name (manufacturer) HA/strain (dosing) |
Mean age (SD) |
Age range | Sex (overall % female) | Vaccination history (overall % previously immunised) | ITT sample size | Relevant outcomes | Author reported conclusions |
| Quadrivalent influenza vaccines (QIV) | |||||||||
| Kramer, 200619 | October 2004– November 2004 USA |
Fluzone (Aventis Pasteur), 15 µg/strain (1×0.5 mL dose) |
NR (>18 years) |
>18 years | NR | NR | 222 | Lab-confirmed influenza (one patient receiving the full dose) Influenza-like illness Adverse events |
There was no significant difference between the full-dose and half-dose groups in the diagnosis of influenza or in the proportion of participants self-reporting four or more symptoms consistent with influenza-like illness. No adverse events were noted by participants from either group or reported to the IRB during the course of the study. |
| Fluzone (Aventis Pasteur), 7.5 µg/strain (1×0.25 mL dose) |
NR (>18 years) |
>18 years | NR | NR | 222 | ||||
| Engler, 200820 | November 2004–December 2004 USA |
Fluzone (Aventis Pasteur), 15 µg/strain (1×0.5 mL dose) |
NR (18–64 years) |
18–64 years | 43.4 | 0 | 554 | Influenza-like illness Hospital/ER visits local and systemic reactogenicity adverse events |
The relative risk of medical visits and hospitalisations for influenza-like illnesses were similar in the half-dose and full-dose group regardless of age, and there was no evidence of ILI symptom differences by sex or dose during the 21 days after immunisations. Although injection site pain was greater for full-dose versus half-dose (19.9% vs 14.4%; p=0.01), when analysed for clinically significant pain levels significant dose-dependent pain differences were not identified. Joint and/or muscle pain were significantly different (p=0.02 and p=0.03, respectively) by dose. No other adverse event differed significantly by dose. |
| Fluzone (Aventis Pasteur), 7.5 µg/strain (1×0.25 mL dose) |
NR (18–64 years) |
18–64 years | 43.4 | 0 | 556 | ||||
| Belshe, 200721 |
NR USA |
Fluzone (Sanofi-Pasteur), 15 µg/strain (1×0.5 mL dose) |
31.5 years (9.6) | 18–49 years | 71.2 | 0 | 31 | Local and systemic reactogenicity | ID vaccine induced significantly more local inflammatory response than intramuscular (IM) vaccine but this did not translate into an increased immune response for ID vaccines compared with IM (primary comparison of this study was ID vs IM doses) |
| Fluzone (Sanofi-Pasteur), 9 µg/strain (1×0.3 mL dose) |
31.2 years (9.4) | 18–49 years | 71.2 | 0 | 32 | ||||
| Fluzone (Sanofi-Pasteur), 6 µg/strain (1×0.2 mL dose) |
30.1 years (10.3) | 18–49 years | 71.2 | 0 | 31 | ||||
| Fluzone (Sanofi-Pasteur), 3 µg/strain (1×0.1 mL dose) |
31.9 years (10.3) | 18–49 years | 71.2 | 0 | 31 | ||||
| Chi, 201022 |
August 2007–2008 USA |
Fluzone (Sanofi Pasteur), 15 µg/strain (1×0.5 mL dose) |
75.6 years (6.8) | >65 years | 17.8 | 94.6 | 65 | Local and systemic reactogenicity adverse events |
The two SAEs were acute coronary syndrome and appendicitis and neither were judged to be related to influenza vaccination |
| Fluzone (Sanofi Pasteur), 9 µg/strain (1×0.3 mL dose) | 75.2 years (7.7) | >65 years | 17.8 | 94.6 | 64 | ||||
HA, haemagglutinin; ID, intradermal; ILI, influenza-like illness; ITT, intention to treat; MDV, multidose vials; N, sample size of treatment arm; NR, not reported; PFS, prefilled syringe; RCT, randomised controlled trial; SAE, serious adverse events.