RV1 Kerdpanich 2010‐THA.

Methods	RCT Length of follow‐up: 2 months post‐dose 2 Adverse event data collection methods: passive; "Diary cards were provided to the parents/guardians of infants to record the solicited general symptoms occurring during the 15 day follow up period after each vaccine dose. The solicited general symptoms were loss of appetite, fussiness/irritability, fever, diarrhoea, vomiting and cough/runny nose. The intensity of each of these symptoms was graded on a 3‐point scale where “0” indicates normal and “3” indicates severe"
Participants	Number: 450 enrolled; ATP safety cohort: 447; ATP immunogenicity cohort: 339 Inclusion criteria: healthy infants aged 6 to 12 weeks at the time of the first vaccination Exclusion criteria: any other investigational drug or vaccine; a history of gastrointestinal disease or rotavirus gastroenteritis; allergy to any of the vaccine components; a history of immunosuppressive or immunodeficient condition
Interventions	1. RIX4414* vaccine reconstituted in buffer stored at 2 °C – 8 °C, n = 174 2. RIX4414* vaccine reconstituted in water stored at 2° C – 8 °C, n = 174 3. RIX4414* vaccine reconstituted in buffer stored at 37 °C for 7 days, n = 50 4. Placebo reconstituted in buffer, n = 26 5. Placebo reconstituted in water, n = 26 * Lyophilized formulation containing at least 106.0 CCID50 of the RIX4414 strain Schedule: 2 doses at month 0 and 2
Outcomes	Clinical outcome measures 1. * Rotavirus diarrhoea, stool sample collected during diarrhoea episode, up to 2 months post‐dose 2 2. * All‐cause diarrhoea, up to 2 months post‐dose 2 3. Reactogenicity, including fever, vomiting and diarrhoea, 15‐day follow‐up period after each dose (collected from GSK report) 4. Serious adverse events, up to 2 months post‐dose 2 5. Fatal serious adverse events 6. Adverse events resulting in discontinuation (collected from GSK report) 7. Dropouts: measured up to 2 months after dose 2 (collected from GSK report) Outcomes to measure immunogenicity 8. Seroconversion, anti‐rotavirus IgA antibody levels (cut off: ≥ 20 U/mL by ELISA ), 2 months post‐dose 2 9. Rotavirus antigen shedding in stool (review includes data from combined time points) (collected from GSK report) * Outcome reported as proportion (P) with 95% CI. Events (n) and totals (N) were estimated by using the values when 2 formulae for the standard error (SE) converged
Immunization status	"During the study period, participating infants were offered commercially available GSK Biologicals’ diphtheria toxoid, tetanus toxoid, acellular pertussis, inactivated polio and H. influenzae type b combination vaccine (InfanrixTM‐IPV/Hib) at two and four months of age and diphtheria toxoid, tetanus toxoid, acellular pertussis, hepatitis B, inactivated polio and H. influenzae type b combination vaccine (Infanrix hexaTM) at six months of age"
Location	2 centres in Thailand WHO mortality stratum B
Notes	Study known as RIX GSK[039] 2007‐AS, in previously published versions of this review Date: March to December 2005 Source of funding: GSK Biologicals Study rationale: This study evaluated the stability of lyophilized RIX4414 vaccine in terms of immunogenicity when reconstituted in water instead of regular buffer, and when stored at tropical room temperature (37 °C) for 7 days before reconstitution
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	Central allocation
Blinding (performance bias and detection bias) All outcomes	High risk	Partially blind study. Quote: “Single blind”, not reported whether personnel or participants were blinded Quote: “The placebo was identical in appearance and composition to the active vaccine”
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition balanced across groups with reasons for withdrawal reported
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	No apparent other bias