RV1 Omenaca 2012‐EU

Methods	RCT Length of follow‐up: 30 to 83 days after dose 2 Adverse events data collection methods: active surveillance: at each study visit parents were asked about AEs; passive surveillance: throughout the trial, parents were asked to immediately report AEs to the investigator
Participants	Number: 1009 Age range: 6 to 12 weeks of age at the time of the first study vaccination Inclusion criteria: medically stable pre‐term infants, born within a gestational period of 27 ‐ 36 weeks, planned to be discharged from hospital's neonatal stay on or before the day of the first human rotavirus vaccine/placebo administration Exclusion criteria: use of any investigational or non‐registered product (drug or vaccine) other than the human rotavirus vaccine within 30 days preceding the first dose of human rotavirus vaccine; any clinically significant history of chronic gastrointestinal disease; any confirmed or suspected immunosuppressive or immunodeficient condition; history of allergic disease; major congenital defects or serious chronic illness Each study group is further stratified into 2 subgroups depending on the gestational age at birth of the participant: Stratum I: very pre‐term infants, born after a gestational period of 27 to 30 weeks (189 to 216 days) (20% of enrolment); Stratum II: mild pre‐term infants born after a gestational period of 31 to 36 weeks (217 to 258 days) (80% of enrolment)
Interventions	1. RV1, 670 participants 2. Placebo, 339 participants Schedule: 2 oral doses of vaccine or placebo, 1 dose at day 0 and 1 dose at months 1 or 2, depending on the country
Outcomes	Clinical outcome measures 1. Serious adverse events, including fatal events and intussusception, from day 0 up to 83 days after dose 2 of RV1 vaccine/placebo 2. Solicited symptoms, within 15 days after each RV1 vaccine/placebo dose. Solicited symptoms included diarrhoea (3 or more looser than normal stools/day), fever (axillary temperature over 37.5 °C), irritability, loss of appetite, and vomiting 3. All‐cause gastroenteritis and rotavirus gastroenteritis, from dose 1 up to 83 days after dose 2 of RV1 vaccine/placebo. Gastroenteritis: diarrhoea with or without vomiting. Rotavirus gastroenteritis: a gastroenteritis episode was a rotavirus gastroenteritis episode if a stool sample taken during or not later than 7 days after the episode was rotavirus positive by ELISA 4. Dropouts before the end of the trial Outcomes to measure immunogenicity 5. Seroconversion to anti‐rotavirus IgA antibody, at Visit 3, 1 month after Dose 2 of RV1 vaccine/placebo. Number of participants with anti‐rotavirus IgA antibody concentration over 20 units/mL
Immunization status	In accordance with the local National Plan of Immunisation schedule in each of the respective participating countries, GSK Biologicals' Infanrix Hexa® (DTPa‐HBV‐IPV/Hib), Infanrix Quinta® (DTPa‐IPV‐Hib), Infanrix®+IPV+Hib (DTPa+IPV+Hib) and/or Engerix‐B® (HBV) will be co‐administered (at a maximum interval of 2 days from each other) with each human rotavirus vaccine or placebo dose Hepatitis B and BCG vaccines at birth are allowed if included in the local National Plan of Immunisation schedule in participating countries At the discretion of the investigator the following vaccines may be administered during each infant's study participation: Vaccine against S. pneumoniae (Prevenar®) in France and Spain (concomitantly with human rotavirus vaccine/placebo). Vaccine against Neisseria meningitidis (Neis Vacc C®) is allowed if there is at least a 14‐day interval with respect to the administration of the human rotavirus vaccine/placebo
Location	France, Poland, Portugal, Spain WHO mortality strata A, B
Notes	Study known as RV1 NCT00420745 2009‐EU in previously published versions of this review Date: January 2007 to March 2008 Source of funding: GlaxoSmithKline Registration number: NCT00420745
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated block randomizations
Allocation concealment (selection bias)	Low risk	Central allocation
Blinding (performance bias and detection bias) All outcomes	Low risk	Parent/guardian and study personnel were not aware of the treatment administered
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data balanced between groups
Selective reporting (reporting bias)	Low risk	All expected outcomes included
Other bias	Low risk	No apparent other bias