Eff ect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials

Methods In two consecutive (primary and booster) randomised, controlled, open-label vaccination studies, 459 healthy infants were enrolled from ten centres in the Czech Republic. Infants were randomly assigned with a computergenerated randomisation list to receive three prophylactic paracetamol doses every 6–8 h in the fi rst 24 h (n=226) or no prophylactic paracetamol (n=233) after each vaccination with a ten-valent pneumococcal non-typeable Haemophilus infl uenzae protein D-conjugate vaccine (PHiD-CV) co-administered with the hexavalent diphtheria-tetanus-3component acellular pertussis-hepatitis B-inactivated poliovirus types 1, 2, and 3-H infl uenzae type b (DTPa-HBVIPV/Hib) and oral human rotavirus vaccines. The primary objective in both studies was the reduction in febrile reactions of 38·0°C or greater in the total vaccinated cohort. The second objective was assessment of immunogenicity in the according-to-protocol cohort. These studies are registered with ClinicalTrials.gov, numbers NCT00370318 and NCT00496015.