RV5 Armah 2010‐KEN

Methods	RCT Length of follow‐up: up to 43 days for safety outcomes, and up to 21 months for efficacy outcomes Adverse event data collection methods: "Study physicians reported and documented all serious adverse events occurring within 14 days of any dose and deaths or vaccine‐related serious adverse events occurring at any time during the study" A subset had active surveillance: "A subset of 300 participants enrolled in Kenya was followed up for 42 days for all adverse events, including vomiting, diarrhoea, and high temperature. Home visits were attempted on days 3, 5, 7, 14, 21, and 42 after all vaccinations".
Participants	Number: 1322 enrolled; 1308 evaluable Age range: 1 to 3 months (beginning); 3 to 6 months (end) Inclusion criteria: healthy infants aged 4 to 12 weeks; "no symptoms of active gastrointestinal disease and could be adequately followed up for safety by home visit or telephone contact (1 week and 2 weeks after any dose of vaccine or placebo)"; breast‐feeding was not restricted; no enrolment restrictions based on HIV status ‐ infants in Kenya were offered routine HIV testing, and a subset were followed up for safety All children exposed to or infected with HIV were referred for appropriate HIV care and treatment; voluntary counselling and testing were also offered to mothers of infants exposed to HIV Exclusion criteria: see above Special group: HIV‐infected participants
Interventions	RV5 1. WC3 (RV5): 2 mL (every dose had an estimated potency of 107 infectious units per reassortant rotavirus); 3 doses given 4 weeks apart; 656 participants (received at least one dose) 2. Placebo: 2 mL; 3 doses given 4 weeks apart; 652 participants (received at least one dose) Schedule: 3 doses given at a 4 week interval
Outcomes	Clinical outcome measures (safety and efficacy) 1. Serious adverse events (including intussusception) 2. Death due to serious adverse events 3. Rotavirus diarrhoea: case definition for rotavirus gastroenteritis required participants to meet both of the following criteria: (1) ≥ 3 watery or looser‐than‐normal stools within a 24‐hour period or forceful vomiting, or both, and (2) rotavirus detected by EIA in a stool specimen taken within 14 days after the onset of symptoms 4. Severe rotavirus diarrhoea: an established clinical scoring system based on the intensity and duration of fever, vomiting, diarrhoea, and changes in behaviour used to categorize episodes of rotavirus gastroenteritis on a 20‐point severity scale; scores > 11 were considered to indicate severe disease; measured up to 2 years follow‐up 5. All‐cause diarrhoea 6. All‐cause diarrhoea – severe 7. Reactogenicity*: symptoms of rotavirus illness, including fever, diarrhoea, and vomiting; measured for 7 days after each dose (review includes data from for the end of follow‐up) *Data on fever and vomiting are provided only on figure 2 and data could not be extracted reliably Outcomes to measure immunogenicity 8. Seroconversion: serum rotavirus IgA responses (increases in level of serum rotavirus IgA ≥ 4‐fold) (review includes data from after dose 2)
Immunization status	All children in the study received the standard EPI vaccines (including oral poliovirus vaccine) starting at 6 weeks of age
Location	Sites in rural Karemo division, Siaya district, Kenya WHO mortality stratum E
Notes	This trial was conducted in Ghana, Kenya and Mali; this part presents data for the Kenya cohort. Data reported separately for the other countries can be found under RV5 Armah 2010‐GHA and RV5 Armah 2010‐MLI, and for all countries under RV5 Armah 2010‐AF Date: 28 April 2007 to 31 March 2009 Source of funding: funded by PATH (GAVI Alliance grant) and Merck Registration number: NCT00362648
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Unique allocation numbers were designated at Merck as pentavalent rotavirus vaccine or placebo with computer generated block randomization, with block sizes of six"
Allocation concealment (selection bias)	Low risk	Quote: "Vaccine and placebo packages were then labelled with allocation numbers and provided to sites in identical presentations. Sites were instructed to assign allocation numbers to participants in sequential order as they were enrolled"
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and staff Quote: "Participants were enrolled by study staff, who remained masked to treatment assignment throughout the trial" Researchers Quote: "The statistician from Merck who analysed the data and the Merck and PATH protocol teams were masked to treatment assignment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data balanced across groups
Selective reporting (reporting bias)	Low risk	Prespecified outcomes reported
Other bias	Low risk	No apparent other bias