NCT01235949

Brief Summary

The aim of the current study is to determine whether ibuprofen, given as immediate or delayed prophylactic antipyretic treatment in a standardized manner, significantly impacts the immune response in children receiving primary vaccination with GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal conjugate vaccine, co-administered with DTPa-combined vaccines, at 3, 4 and 5 months of age. In addition, this study will further evaluate the impact of prophylactic administration of paracetamol following primary vaccination with immediate or delayed administration or when given in an immediate manner at the time of the booster dose.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
850

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2010

Typical duration for phase_4

Geographic Reach
1 country

23 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 4, 2010

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 8, 2010

Completed
4 days until next milestone

Study Start

First participant enrolled

November 12, 2010

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 28, 2012

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 8, 2012

Completed
6.2 years until next milestone

Results Posted

Study results publicly available

January 31, 2019

Completed
Last Updated

May 10, 2019

Status Verified

April 1, 2019

Enrollment Period

1.4 years

First QC Date

November 4, 2010

Results QC Date

September 29, 2017

Last Update Submit

April 25, 2019

Conditions

Keywords

Pneumococcal vaccineImmunogenicitySafetyFeverPrimary vaccinationBooster vaccinationPneumococcal diseaseProphylactic antipyretic

Outcome Measures

Primary Outcomes (3)

  • Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes Greater Than or Equal to (≥) the Cut-off

    Antibodies against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) have been assessed by 22F-inhibition enzyme-linked immunosorbent assay (ELISA). The cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.2 micrograms per milliliter (μg/mL).

    One month after primary immunization (At Month 3)

  • Antibody Concentrations Against Vaccine Pneumococcal Serotypes

    Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was an antibody concentration ≥ 0.05 μg/mL.

    One month after primary immunization (At Month 3)

  • Antibody Concentrations Against Protein D (Anti-PD)

    Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units (EL.U) per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 100 EL.U/mL.

    One month after primary immunization (At Month 3)

Secondary Outcomes (22)

  • Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A

    One month after primary immunization (At Month 3)

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms

    Within the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms

    Within the 4-day (Days 0-3) period following booster vaccination

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    Within the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    Within the 4-day (Days 0-3) period following booster vaccination

  • +17 more secondary outcomes

Study Arms (18)

Group IIBU

EXPERIMENTAL

Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group DIBU

ACTIVE COMPARATOR

Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group NIBU

ACTIVE COMPARATOR

No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib

Group IPARA

EXPERIMENTAL

Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Paracetamol

Group DPARA

EXPERIMENTAL

Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Paracetamol

Group NPARA

ACTIVE COMPARATOR

No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib

Group IIBU-IIBU

EXPERIMENTAL

1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group IIBU-DIBU

EXPERIMENTAL

1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib

Group IIBU-NIBU

EXPERIMENTAL

1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group DIBU-IIBU

EXPERIMENTAL

1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group DIBU-DIBU

EXPERIMENTAL

1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group DIBU-NIBU

EXPERIMENTAL

1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib

Group NIBU-IIBU

EXPERIMENTAL

1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group NIBU-DIBU

EXPERIMENTAL

1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Ibuprofen

Group NIBU-NIBU

ACTIVE COMPARATOR

1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib

Group IPARA-NPARA

EXPERIMENTAL

subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/Hib

Group DPARA-IPARA

EXPERIMENTAL

subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Paracetamol

Group NPARA-IPARA

EXPERIMENTAL

subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination

Biological: GSK1024850A (SynflorixTM)Biological: Infanrix hexaBiological: Infanrix-IPV/HibDrug: Paracetamol

Interventions

Intramuscular injection, 4 doses

Group DIBUGroup DIBU-DIBUGroup DIBU-IIBUGroup DIBU-NIBUGroup DPARAGroup DPARA-IPARAGroup IIBUGroup IIBU-DIBUGroup IIBU-IIBUGroup IIBU-NIBUGroup IPARAGroup IPARA-NPARAGroup NIBUGroup NIBU-DIBUGroup NIBU-IIBUGroup NIBU-NIBUGroup NPARAGroup NPARA-IPARA
Infanrix hexaBIOLOGICAL

Intramuscular injection, 3 doses

Group DIBUGroup DIBU-DIBUGroup DIBU-IIBUGroup DIBU-NIBUGroup DPARAGroup DPARA-IPARAGroup IIBUGroup IIBU-DIBUGroup IIBU-IIBUGroup IIBU-NIBUGroup IPARAGroup IPARA-NPARAGroup NIBUGroup NIBU-DIBUGroup NIBU-IIBUGroup NIBU-NIBUGroup NPARAGroup NPARA-IPARA

Intramuscular injection, 1 dose

Group DIBUGroup DIBU-DIBUGroup DIBU-IIBUGroup DIBU-NIBUGroup DPARAGroup DPARA-IPARAGroup IIBUGroup IIBU-DIBUGroup IIBU-IIBUGroup IIBU-NIBUGroup IPARAGroup IPARA-NPARAGroup NIBUGroup NIBU-DIBUGroup NIBU-IIBUGroup NIBU-NIBUGroup NPARAGroup NPARA-IPARA

Oral administration, 3 doses in the 24 hours following vaccination with an interval of 6-8 hours between doses and with dosage based on the subject's body weight

Also known as: Nurofen for Children
Group DIBUGroup DIBU-DIBUGroup DIBU-IIBUGroup IIBUGroup IIBU-IIBUGroup IIBU-NIBUGroup NIBU-DIBUGroup NIBU-IIBU

Oral administration, 3 doses in the 24 hours following vaccination with an interval of 6-8 hours between doses and with dosage based on the subject's body weight

Also known as: Panadol Baby
Group DPARAGroup DPARA-IPARAGroup IPARAGroup NPARA-IPARA

Eligibility Criteria

Age12 Weeks - 16 Weeks
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
  • A male or female between, and including, 12 and 16 weeks (84-118 days) of age at the time of the first vaccination.
  • Written informed consent obtained from the parent(s)/LAR(s) of the subject.
  • Free of obvious health problems as established by medical history and clinical examination before entering into the study.
  • Born after a gestation period of 36 to 42 weeks inclusive.

You may not qualify if:

  • Use of any investigational or non-registered product other than the study vaccines/products within 30 days preceding the first dose of study vaccine/product, or planned use during the study period.
  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (.
  • Indication, other than specified in the protocol, for prophylactic or therapeutic antipyretic treatment during the study period.
  • Treatment with antipyretics in the 24 hours before study vaccination or planned administration of antipyretics in the 24 hours after study vaccination.
  • Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
  • Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of study vaccine and ending 30 days after with the exception of locally recommended (pandemic) influenza vaccines, and those should be documented in the eCRF.
  • Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae with the exception of the vaccines where the first dose may be given within the first two weeks of life according to the national recommendations.
  • History of intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease.
  • History of any allergic disease or reaction likely to be exacerbated by any component of the vaccines or prophylactic antipyretic treatment, i.e. ibuprofen or paracetamol, as specified in the protocol.
  • History of any seizures or progressive neurological disease.
  • Acute disease and/or fever at the time of enrolment. The study entry should be delayed until the illness has improved.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination .
  • A family history of congenital or hereditary immunodeficiency.
  • Major congenital defects or serious chronic illness.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during entire study period.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (23)

GSK Investigational Site

Bacau, 600316, Romania

Location

GSK Investigational Site

Brasov, 500063, Romania

Location

GSK Investigational Site

Brasov, 500260, Romania

Location

GSK Investigational Site

Brasov, 500366, Romania

Location

GSK Investigational Site

Brăila, 810289, Romania

Location

GSK Investigational Site

Brăila, 810346, Romania

Location

GSK Investigational Site

Bucharest, 030442, Romania

Location

GSK Investigational Site

Bucharest, 050734, Romania

Location

GSK Investigational Site

Bucharest, 051821, Romania

Location

GSK Investigational Site

Bucharest, 077190, Romania

Location

GSK Investigational Site

Călăraşi, 910160, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400217, Romania

Location

GSK Investigational Site

Constanța, 900709, Romania

Location

GSK Investigational Site

Constanța, 900721, Romania

Location

GSK Investigational Site

Galati, 800099, Romania

Location

GSK Investigational Site

Galati, 800179, Romania

Location

GSK Investigational Site

Galati, 800235, Romania

Location

GSK Investigational Site

Galati, 800322, Romania

Location

GSK Investigational Site

Galati, 800394, Romania

Location

GSK Investigational Site

Iași, 700115, Romania

Location

GSK Investigational Site

Pantelimon, 77145, Romania

Location

GSK Investigational Site

Sibiu, 550166, Romania

Location

GSK Investigational Site

Timișoara, 300593, Romania

Location

Related Publications (1)

  • Falup-Pecurariu O, Man SC, Neamtu ML, Chicin G, Baciu G, Pitic C, Cara AC, Neculau AE, Burlea M, Brinza IL, Schnell CN, Sas V, Lupu VV, Francois N, Swinnen K, Borys D. 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. Hum Vaccin Immunother. 2017 Mar 4;13(3):649-660. doi: 10.1080/21645515.2016.1223001. Epub 2016 Aug 19.

    PMID: 27541270BACKGROUND

Related Links

MeSH Terms

Conditions

Streptococcal InfectionsFeverPneumococcal Infections

Interventions

diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccineIbuprofenAcetaminophen

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsBody Temperature ChangesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhenylpropionatesAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsAcetanilidesAnilidesAmidesAniline CompoundsAmines

Results Point of Contact

Title
GSK Response Center
Organization
GlaxoSmithKline

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
FACTORIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 4, 2010

First Posted

November 8, 2010

Study Start

November 12, 2010

Primary Completion

March 28, 2012

Study Completion

December 8, 2012

Last Updated

May 10, 2019

Results First Posted

January 31, 2019

Record last verified: 2019-04

Data Sharing

IPD Sharing
Will share

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Available IPD Datasets

Informed Consent Form (112921)Access
Individual Participant Data Set (112921)Access
Statistical Analysis Plan (112921)Access
Clinical Study Report (112921)Access
Dataset Specification (112921)Access
Study Protocol (112921)Access

Locations