RV1 Vesikari 2004a‐FIN

Methods	RCT Length of follow‐up: 8 to 30 days after each dose Adverse event data collection methods: diary cards provided to participants or participants' parents/guardians to record solicited general symptoms on the day of each vaccination and for 7 subsequent days (passive method)
Participants	Number: 192 enrolled; 178 evaluable Age range: 1 to 3 months (beginning); 3 to 6 months (end) Inclusion criteria: healthy infants, born after a normal gestation period of 36 to 42 weeks; 6 to 12 weeks of age at the time of the first dose of the study vaccination course; free of obvious health problems as established by medical history and clinical examination before entering into the study Exclusion criteria: participating in any other clinical trial; acute disease; history of allergic reaction to any vaccine component; history of chronic gastrointestinal disease or other serious medical condition; undergone immunosuppressive therapy; received antibiotics within 14 days preceding the study vaccine administration and during the first 7 days after vaccine administration; any confirmed or suspected immunosuppressive or immunodeficient condition, had received any immunoglobulin therapy or blood products before start or during the trial; abnormal stool pattern or household contact with an immunosuppressed individual or pregnant woman; for the infants, previous confirmed occurrence of rotavirus gastroenteritis
Interventions	RV1 1. RIX4414 (RV1) 1.1. 104.1 PFU; 32 participants (randomized) 1.2. 104.7 PFU; 64 participants (randomized) * 1.3. 105.8 PFU; 32 participants (randomized) 2. Placebo: 64 participants (randomized) Schedule: 2 doses given 2 months apart *Half of infants receiving 104.7 PFU of RV1 were tested with prior administration of Mylanta as buffer; in the other half vaccine was diluted in a buffer containing calcium carbonate Feeding was not allowed for an hour before and after study vaccine administration
Outcomes	Clinical outcome measures (safety and efficacy) 1. Adverse events requiring discontinuation: no definition; measured at 31‐day follow‐up after each dose 2. Serious adverse events: no definition; measured at 31‐day follow‐up after each dose 3. Reactogenicity: no definition; measured at 31‐day follow‐up after each dose 4. Dropouts: no definition; measured at 31‐day follow‐up after each dose 5. All‐cause mortality: no definition; measured at 31‐day follow‐up after each dose Outcomes to measure immunogenicity 6. Rotavirus shedding in stool (review includes data from day 7 to 9 after dose 2) 7. Seroconversion: appearance of serum anti‐rotavirus IgA antibody to rotavirus in post‐vaccination sera at a titre of ≥ 20 U/mL in previously uninfected infants; measured in infants only (review includes data from 2 months after dose 1 and 1 month after dose 2)
Immunization status	Infant routine vaccinations were separated from the study vaccines by 2 weeks
Location	2 centres in Finland WHO mortality stratum A
Notes	Date: 29 May to 18 December 2000 Source of funding: GlaxoSmithKline Biologicals Trial report also includes results for a study in adults and in previously rotavirus‐infected children; neither included in this review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated, using a SAS programme
Allocation concealment (selection bias)	Low risk	Likely to be adequate: treatment masked to investigators Quote: "A randomisation or subject number identified uniquely the vaccine dose to be administered to the subject", and "subjects were administered the vaccine dose with the lowest number available at the study site"
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Quote: "The study was performed under double‐blind with respect to the groups within each study part"
Incomplete outcome data (attrition bias) All outcomes	Low risk	14/192 participants dropped out of the study, balanced between groups with reasons provided.
Selective reporting (reporting bias)	Low risk	All planned outcomes were reported
Other bias	Unclear risk	No information