Nonetheless, in pre-licensure trials, it is critical to remain vigilant to the risk of intussusception in trial participants and to determine

if there are safety signals of larger magnitude than currently expected that might preclude licensure. We describe the surveillance for intussusception among children enrolled in a phase III clinical trial for safety and efficacy and present some of the lessons learnt that might be relevant as countries plan post marketing surveillance for intussusception prior to or following introduction of vaccines in their NIP. Participants were enrolled, after written informed consent was obtained, in a phase III, double-blind placebo-controlled, randomized clinical trial to evaluate the efficacy of three doses of Rotavac against severe selleck inhibitor rotavirus gastroenteritis Selleckchem PFI-2 which was conducted at three

sites (Delhi, Pune and Vellore) in India between 2010 and 2013. The ethics review committees of participating sites approved the protocol. Subjects recruited between 6 and 7 weeks of age were randomized in a 2:1 ratio to receive 3 doses of vaccine or a placebo. Routine childhood vaccines were co-administered and breastfeeding was not restricted. The first one third of the participants enrolled in the study at all three sites were included in a detailed safety follow which involved study staff making daily contact for fourteen days after each dose of vaccine to solicit information on occurrence of solicited adverse events. All children recruited in the trial were also followed up weekly until the age of 2 years for safety and efficacy endpoints. Primary caregivers were provided a mobile phone and access to the study team round the clock and Sclareol were advised to contact the study team whenever the child had an episode of gastroenteritis, signs and symptoms of intussusception or any illness that required hospital referral. The study used broad screening criteria for suspected intussusception to ensure all intussusceptions were identified early and treated appropriately. All

children who had three or more episodes of vomiting in an hour or blood in stool or complaints of abdominal distension with an increase in abdominal girth of 2 cm or more in a 4 h period or an abdominal mass palpable per abdomen were considered to have a suspected intussusception event. Every subject with suspected intussusception was examined by the study team and taken for pediatric consultation and hospitalized, if required. Ultrasonography was performed within eight hours and a pediatric surgeon consulted if advised by the pediatrician. Pediatric surgeons assessed children with evidence of intussusception on ultrasonography and instituted appropriate management as per treating facility protocol. All children who presented with blood in stool along with one other finding suggestive of intussusception had stool samples tested for rotavirus shedding at a central laboratory.