ActivePhase 4ACTRN12617000065392

OPTimising IMmunisation Using Mixed schedules (OPTIMUM): comparing allergic outcomes in infants following pertussis vaccination

A double-blind, randomised, controlled trial to compare allergic outcomes in children following vaccination with acellular pertussis antigen given at 2 months of age versus whole cell pertussis in the infant vaccine schedule

Sponsor

University of Sydney

Enrollment

3,000 participants

Start Date

Mar 7, 2018

Study Type

Interventional

Conditions

Pertussis vaccination Allergy

Summary

The rise in atopy, particularly food allergy, over recent decades in Australia has coincided with a change from the routine use of Whole cell pertussis vaccination (DTwP) to Acellular pertussis vaccination (DTaP). These events may be causally related via the differential modulation of the Th1 and Th2 arms of the immune system by the different vaccines. A single first dose of DTwP followed by two doses of DTaP in the infant vaccination schedule may allow a more balanced immune response, and protection from subsequent atopy. Although a full DTwP vaccine course is more reactogenic than a full DTaP vaccine course, this may not be true for a single dose of DTwP given in early infancy. Furthermore, substitution of the first DTaP dose with DTwP may significantly reduce the frequency of extensive limb swelling observed after the 18 month and 4 year old booster doses of DTaP. An assessment of the immune responses of contemporary Australian infants primed with either a mixed DTwP/DTaP or the current DTaP-only schedule is warranted. Infants will receive either a combined Diphtheria-Tetanus-whole cell Pertussis, Hepatitis B, and Haemophilus influenzae type B vaccine (DTwP-HepB-Hib) OR a combined Diphtheria-Tetanus-acellular Pertussis, Hepatitis B, Inactivated Poliovirus and Haemophilus influenzae type B vaccine (DTaP-HepB-IPV-Hib) as their first vaccine dose at 6- <12 weeks of age as part of the infant vaccine schedule. All infants will then receive DTaP-HepB-IPV-Hib at 4 and 6 months of age and combined Diphtheria-Tetanus-acellular Pertussis (DTPa) and Inactivated Poliovirus at 18 months of age, along with vaccines prescribed by the standard Australian Immunisation Schedule. The dose and route of vaccination will be consistent with the manufacturer’s instruction. The primary objective of the study is to assess the allergy protective benefits of the addition of DTwP into the infant schedule. Infants will be assessed for development of allergic disease and atopic sensitisation. The study will also assess the reactogenicity profile of the whole cell vaccine within stage 1 and the first 150 participants of stage 2 of this two staged trial. If DTwP is found to be acceptable to parents and protective against the development of atopic disease this could have profound implications for vaccine policy in Australia and around the world.

Eligibility

Sex: Both males and femalesMin Age: 6 WeekssMax Age: 11 Weekss

Inclusion Criteria10

An eligible infant must fulfill all of the following:
Healthy male or female infant aged 6 to 11 weeks and 6 days old
Born on or after 32 weeks
Parent or guardian understands the information provided and is willing and able to give informed consent for participation in the trial
Infant known to be free of significant medical problems as determined by a medical history and clinical examination by a medically qualified investigator
Parent has access to a telephone
Parent or guardian who is able and willing to comply with the requirements of the protocol in the opinion of an investigator
Willing to allow his or her general practitioner and/or paediatrician and/or immunisation provider and/or other parties involved in the treatment of their child , to be notified of participation in the trial
Willing to allow the study team to obtain information from the infant’s doctor, other health care professionals, hospitals or laboratories concerning the infant’s health from enrolment until 1 month after the 18-month vaccinations.
Be available for the entire study period

Exclusion Criteria15

The participant may not enter the trial if ANY of the following apply:
History of pre-existing parent-reported clinician diagnosed IgE-mediated food allergy
History of pertussis infection
Receipt of any prior vaccine, except for a single birth dose of hepatitis B vaccine within the first 7 days of life.
Contra-indication to any routine infant immunisation: History of allergy, including anaphylaxis, to any vaccine or vaccine component
Contra-indication to paracetamol
Receipt of investigational vaccines/drugs, other than the vaccines used in the study, since birth or their planned use during the study period, until the final study visit (i.e. at approximately 19 months of age).
Receipt, or planned receipt, of any non-routine vaccines within 14 days after the first dose of pertussis containing vaccine
Receipt of more than 2 weeks of immunosuppressants or immune modifying drugs, (e.g. prednisolone >0.5mg/kg/day)
Serious chronic illness including severe congenital anomalies affecting heart, brain and/or lungs.
History of any neurologic disorders or seizures
Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period
Planned travel to any country that remains at risk of a poliomyelitis outbreak at any time before the final phone/electronic contact (i.e. at approximately 19 months of age.)
Parents who plans to move out of the geographical area where the study would be conducted
Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.

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Interventions

0.5ml,Pentabio vaccine (Diphtheria-Tetanus-Pertussis (whole cell)-Hepatitis B- haemophilus influenzae type b) administered by intramuscular injection at approximately 6 to <12 weeks of age, together with the standard schedule of vaccines in accordance with the current Australian National Immunisation Program Schedule (group 1) 0.5ml of Infanrix Hexa (Diphtheria, Tetanus, acellular Pertussis, Hepatitis B, Polio, and Haemophilus influenzae type b (DTaP-HB-IPV-Hib) administered by intramuscular injection at approximately 4 and 6 months of age. 0.5ml of Infanrix-IPV (Combined Diphtheria-Tetanus-acellular Pertussis (DTPa) and Inactivated Poliovirus) administered by intramuscular injection at approximately 18 months of age. Each participant in the intervention group will receive the above 4 vaccines.