3994
study participant
s were enrolled fro
m six countrie
s and were rando
mly a
ssigned two oral do
se
s of either RIX4414 (n=2646) or placebo (n=1348), which were coad
mini
stered with the fir
st two do
se
s of
specific childhood vaccination
s. Follow-up for ga
stroenteriti
s epi
sode
s wa
s undertaken fro
m 2 week
s po
st-do
se two through the two con
secutive rotaviru
s sea
son
s following vaccination
s (co
mbined efficacy follow-up period;
mean duration 17
month
s [SD 1·6]). Our pri
mary endpoint wa
s vaccine efficacy again
st rotaviru
s ga
stroenteriti
s of any
severity during the fir
st efficacy follow-up period (2 week
s po
st-do
se two to the end of the fir
st rotaviru
s sea
son). Stool
speci
men
s obtained during ga
stroenteriti
s epi
sode
s were te
sted for rotaviru
s by ELISA and typed by RT-PCR. Epi
sode
s scoring 11 or greater on the 20-point Ve
sikari
scale were cla
ssified a
s severe. Analy
si
s wa
s according to protocol. Thi
s study i
s regi
stered with ClinicalTrial
s.gov, nu
mber NCT00140686 (eTrack102247).
ss="h4">Findings
120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5·7 months [SD 1·2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87·1%(95%CI 79·6–92·1; p<0·0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90·4%(85·1–94·1; p<0·0001), for admission owing to rotavirus gastroenteritis 96·0%(83·8–99·5; p<0·0001), and for rotavirus-related medical attention 83·8%(76·8–88·9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown.
ss="h4">Interpretation
In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.