RV1 Li 2014‐CHN

Methods	RCT Length of follow‐up: 2 years Adverse event data collection methods: (not reported if active or passive) serious adverse events were recorded throughout the study period
Participants	Number: 3333 enrolled; 3148 evaluable Age range: 6 to 16 weeks Inclusion criteria: participants who the investigator believes that their parents/LARs can and will comply with the requirements of the protocol, male or female infant of Chinese origin between, and including, 6 and 16 weeks of age at the time of the first vaccination, healthy infants as established by medical history and clinical examination before entering into the study, born after a gestation period of 36 to 42 weeks inclusive Exclusion criteria: child in care; use of any investigational or non‐registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period; any clinically significant history of gastrointestinal disease; any confirmed or suspected immunosuppressive or immunodeficient condition; history of confirmed rotavirus gastroenteritis; acute disease and/or fever at the time of enrolment; gastroenteritis within 7 days preceding the study vaccine or placebo administration
Interventions	2 cohorts 1. 1st RV season RIX4414 (1575 participants) or placebo (1573 participants) 2. 2nd RV season RIX4414 (1500 participants) or placebo (1479 participants) Schedule: 2 doses of Rotarix™ vaccine, liquid formulation, at day 0 and at month 1
Outcomes	Clinical outcome measures (safety and efficacy) 1. All‐cause diarrhoea, severe and any severity 2. Rotavirus diarrhoea, severe and any severity 3. Rotavirus diarrhoea requiring hospitalization 4. All‐cause mortality 5. Serious adverse events 6. Intussusception 7. Reactogenicity: fever, diarrhoea, vomiting 8. Adverse events requiring discontinuation 9. Dropouts before end of the trial Outcomes to measure immunogenicity 10. Seroconversion
Immunization status	As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, participants also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccines were administered independently of (sub‐cohort 1) or concomitantly with (sub‐cohort 2) the Rotarix™ vaccine. When administered concomitantly, participants received the 3 doses of Infanrix™ vaccine at months 1, 2, and 3, and the 3 doses of the OPV vaccine at day 0, month 1 and month 2. The Rotarix™ and OPV vaccines were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh
Location	4 sites, China WHO mortality stratum B
Notes	Date: August 2010 to May 2012 Source of funding: GlaxoSmithKline Study rationale: The aim of this study was to assess the efficacy, immunogenicity and safety of two doses of GSK Biologicals’ HRV vaccine in healthy Chinese infants aged between 6 and 16 weeks at the time of the first dose of vaccination.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization sequence generated using software (MATEX developed for SAS)
Allocation concealment (selection bias)	Low risk	Treatment allocation at the investigator site was performed using SBIR (internet randomization tool)
Blinding (performance bias and detection bias) All outcomes	Low risk	Concealed from parents/guardians, study personnel, and investigators, placebo‐controlled study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons for attrition provided
Selective reporting (reporting bias)	Low risk	Planned outcomes fully reported
Other bias	Low risk	No apparent other bias