title: Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine (PHiD-CV) co-administered with DTPa-combined vaccines in children: An open-label, randomized, controlled, non-inferiority trial.
abstract: Prophylactic paracetamol administration impacts vaccine immune response; this study ( www.clinicaltrials.gov : NCT01235949) is the first to assess PHiD-CV immunogenicity following prophylactic ibuprofen administration. In this phase IV, multicenter, open-label, randomized, controlled, non-inferiority study in Romania (November 2010-December 2012), healthy infants were randomized 3:3:3:1:1:1 to prophylactically receive immediate, delayed or no ibuprofen (IIBU, DIBU, NIBU) or paracetamol (IPARA, DPARA, NPARA) after each of 3 primary doses (PHiD-CV at age 3/4/5 months co-administered with DTPa-HBV-IPV/Hib at 3/5 and DTPa-IPV/Hib at 4 months) or booster dose (PHiD-CV and DTPa-HBV-IPV/Hib; 12-15 months). Non-inferiority of immune response one month post-primary vaccination in terms of percentage of infants with anti-pneumococcal antibody concentrations ≥0.2 µg/mL (primary objective) was demonstrated if the upper limit (UL) of the 98.25% confidence interval of difference between groups (NIBU vs IIBU, NIBU vs DIBU) was <10% for ≥7/10 serotypes. Immunogenicity and reactogenicity/safety were evaluated, including confirmatory analysis of difference in fever incidences post-primary vaccination in IBU or DIBU group compared to NIBU. Of 850 infants randomized, 812 were included in the total vaccinated cohort. Non-inferiority was demonstrated for both comparisons (UL was <10% for 9/10 vaccine serotypes; exceptions: 6B [NIBU], 23F [IIBU]). However, fever incidence post-primary vaccination in the IIBU and DIBU groups did not indicate a statistically significant reduction. Prophylactic administration (immediate or delayed) of paracetamol decreased fever incidence but seemed to reduce immune response to PHiD-CV, except when given only at booster. Twenty-seven serious adverse events were reported for 15 children; all resolved and were not vaccination-related.
authors.affiliation: a Department of Pediatrics, Children's Clinic Hospital, Faculty of Medicine , Transilvania University , Brasov , Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Falup-Pecurariu
authors.affiliation: b Mother and Child Department , University of Medicine and Pharmacy "Iuliu Hatieganu ," Cluj-Napoca , Romania.
authors.forename: Sorin C
authors.initials: SC
authors.lastname: Man
authors.affiliation: c Pediatric Clinic , Pediatric Clinic Hospital Sibiu , Sibiu , Romania.|d Medical Department , Lucian Blaga University of Sibiu , Sibiu , Romania.
authors.forename: Mihai L
authors.initials: ML
authors.lastname: Neamtu
authors.affiliation: e Preventive Medicine Department , Prophylaxis Center , Timisoara , Romania.
authors.forename: Gratiana
authors.initials: G
authors.lastname: Chicin
authors.affiliation: f Department of Pediatrics , Dunarea de Jos University of Galati , Galati , Romania.|g Saint Andrew Children Hospital Galati , Galati , Romania.
authors.forename: Ginel
authors.initials: G
authors.lastname: Baciu
authors.affiliation: h General Practitioner , Private Practice , Galati , Romania.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pitic
authors.affiliation: i General Practitioner , Private Practice , Calarasi , Romania.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Cara
authors.affiliation: j Fundamental and Prophylactic Sciences Department , Transilvania University , Brasov , Romania.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Neculau
authors.affiliation: k Department of Pediatrics , Grigore T. Popa University of Medicine and Pharmacy , Iasi , Romania.
authors.forename: Marin
authors.initials: M
authors.lastname: Burlea
authors.affiliation: l General Practitioner , Private Practice , Braila , Romania.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Brinza
authors.affiliation: m Third Pediatric Clinic , Emergency Clinical Hospital for Children , Cluj-Napoca , Romania.
authors.forename: Cristina N
authors.initials: CN
authors.lastname: Schnell
authors.affiliation: m Third Pediatric Clinic , Emergency Clinical Hospital for Children , Cluj-Napoca , Romania.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sas
authors.affiliation: k Department of Pediatrics , Grigore T. Popa University of Medicine and Pharmacy , Iasi , Romania.
authors.forename: Valeriu V
authors.initials: VV
authors.lastname: Lupu
authors.affiliation: n GSK , Wavre , Belgium.
authors.forename: Nancy
authors.initials: N
authors.lastname: François
authors.affiliation: o XPE Pharma & Science for GSK , Wavre , Belgium.
authors.forename: Kristien
authors.initials: K
authors.lastname: Swinnen
authors.affiliation: n GSK , Wavre , Belgium.
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000097:blood; D058633:Antipyretics / Q000008:administration & dosage*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D005334:Fever / Q000453:epidemiology; D064368:Healthy Volunteers; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D015994:Incidence; D007223:Infant; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D012383:Romania; D016896:Treatment Outcome
chemical_list: C586648:10-valent pneumococcal conjugate vaccine; D000907:Antibodies, Bacterial; D058633:Antipyretics; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines; D000082:Acetaminophen; D007052:Ibuprofen
keywords: 10-valent pneumococcal conjugate; Ibuprofen; fever; paracetamol; prophylaxis; vaccine