RV1 Narang 2009‐IND

Methods	RCT Length of follow‐up: 1 month after dose 2 Adverse event data collection methods: passive, parents/guardians filled in diary cards of any symptoms
Participants	Number: 363 enrolled; 344 evaluable Age range: 1 to 3 months (beginning); 3 to 6 months (end) Inclusion criteria: healthy male or female infants between and including 8 to 10 weeks of age at the time of first vaccination; free of obvious health problems as established by medical history and clinical examination before entering into the study; Exclusion criteria: history of confirmed rotavirus gastroenteritis or with prior administration of experimental rotavirus vaccine
Interventions	RV1 1. RIX4414 (RV1): 106.5 PFU; 182 participants (randomized) 2. Placebo: 181 participants (randomized) Schedule: 2 oral doses given at age 2 and 4 months
Outcomes	Clinical outcome measures (safety and efficacy) 1. Reactogenicity: for each type of solicited symptom, occurrence of the symptom within the 8‐day (days 0 to 7) solicited follow‐up period after each dose; occurrence of unsolicited adverse events within 31 days (days 0 to 30) after each dose, according to MedDRA classification; measured up to 31 days after vaccine/placebo 2. Serious adverse events: no definition; occurrence throughout entire study period (up to 31 days after vaccine/placebo) 3. Dropouts: no definition; measured up to 31 days after vaccine/placebo 4. Rotavirus diarrhoea: presence of rotavirus in gastroenteritis episode stools collected from dose 1 of RV1 vaccine/placebo up to 2 months after dose 2; measured up to 31 days after vaccine/placebo 5. All‐cause death 6. Adverse events resulting in discontinuation Outcomes to measure immunogenicity 7. Seroconversion: appearance of anti‐rotavirus immunoglobulin A (IgA) antibody concentration ≥ 20 U/mL in participants who were seronegative before vaccination (review includes data from 1 month after dose 2)
Immunization status	Routine vaccinations (diphtheria‐tetanus‐whole cell pertussis‐hepatitis b, H. influenzae type b, and oral poliovirus vaccine) were administered at 6, 10, and 14 weeks of age (given with a 2‐week separation from the first and subsequent dose of the RV1 vaccine or placebo)
Location	4 centres in India WHO mortality stratum D
Notes	Date: 10 February 2006 to 8 September 2006 Source of funding: GlaxoSmithKline Biologicals Study rationale: "to assess the immunogenicity and safety of 2 doses of oral live attenuated human rotavirus vaccine in healthy infants in India"
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 treatment number identified uniquely the vaccine doses to be administered to the same subject" and "subjects were administered the vaccine dose with the lowest treatment number available at the study centre"
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	Attrition/exclusions balanced between groups
Selective reporting (reporting bias)	Low risk	All planned outcomes were reported
Other bias	Low risk	No apparent other bias