Effect of Morning vs. Evening Vaccination on Hypoxia and Bradycardia of Preterm Infants: a Randomised Controled Trial

Study Overview
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Brief Summary
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Hypoxia/bradycardia are common symptoms after vaccination of preterm infants. Adults show diurnal variations in vaccination response, due to circadian regulation of the immune system. The investigators plan to investigate whether preterm infants also show differences in hypoxia/bradycardia rate upon morning vs. evening vaccination. Hypoxia/bradycardia is recorded by pulse oximetry starting 24 hours before until 48 hours after vaccination; parents also kept a sleep-diary. 24 hours after vaccination interleukin-6, interleukin-1β and C-reactive protein get determined. To control vaccination response, pertussis- and haemophilus-titers are determined before vaccination and at 4 months corrected age.

Detailed Description
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Intervention: First hexavalent vaccination given to very preterm infants either in the evening or in the morning. Primary outcome: rate of desaturations (SpO2 <80%) and bradycardias (Pulse rate <100/min) in first 24 h following vaccination in evening vs. morning vaccination group Secondary outcomes: cytokine levels (IL 6, IL 1ß, CRP) measured 24 h after vaccination, pertussis- and haemophilus-titers as measured before and after vaccination, i.e. at 4 months corrected age, in evening vs. morning vaccination group

Official Title
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Effect of Morning vs. Evening Vaccination on Hypoxia and Bradycardia of Preterm Infants: a Randomised Controled Trial

Conditions
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Premature Birth, Intermittent Hypoxiema

Intervention / Treatment
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* Biological: Infanrix + Prevenar 13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational Age: 26+0 to 30+6 Weeks of gestational age Exclusion Criteria: bronchopulmonary dysplasia periventricular leukomalacia intraventricular hemorrhage >°2 congenital malformations

Ages Eligible for Study
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Minimum Age: 30 Days
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: morning vaccination<br>Vaccination with Infanrix + Prevenar 13 between 7 and 10 am | Biological: Infanrix + Prevenar 13<br>* Different time of application<br>|
| Active Comparator: evening vaccination<br>Vaccination with Infanrix + Prevenar 13 between 7 and 10 pm | Biological: Infanrix + Prevenar 13<br>* Different time of application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hypoxia and bradycardia events |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccination titer in blood sample after vaccination compared to vaccination titer in blood sample before vaccination |  | Before vaccination and at the age of 4 months (corrected age) |