Trial Outcomes & Findings for Cardio-respiratory Events and Inflammatory Response After Primary Immunization in Preterm Infants (NCT NCT02726178)

Results Overview

Immunization with the pentavalent vaccine Diphtheria-Tetanus-Acellular pertussis-Inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-IPV-Hib) at two months of age is known to be associated with cardio-respiratory events (CRE), in 11 to 47% of preterm infants.It is considered that the immature brainstem respiratory control of preterms make them more vulnerable to the inflammatory reaction caused by immunization. We hypothesized that post-immunization CRE are correlated with inflammatory reaction. The primary objective was to examine the impact of endogenous PG inhibition on the occurrence of CRE following the first dose of pentavalent vaccine in preterm infants born \< 32 weeks gestation. Total CRE was expressed as the average number of events (desaturation + apneas + bradycardia) / 24 hours. Δ Total CRE / patient / 24 hours was defined as the difference between the average number of events / 24 hours observed before vs. after immunization for each patient.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

56 participants

Primary outcome timeframe

the mean of CRE occured in the 48h after immunization minus the base line CRE : mesured 24h before immunization

Results posted on

2018-05-17

Participant Flow

The recruitment process was conducted in the neonatal intensive care unit of Sainte-Justine University Hospital (CHU Sainte-Justine, Montreal, QC, Canada) over a period of fourteen months (February 2010 - March 2011).

A total of 362 preterm infants were screened, 56 completed the study. Of the infants who did not participate in the study, 212 were discharged before the first immunization (92 to home and 120 to level II nurseries), 37 died, 28 were still intubated at the time of enrolment, 14 did not meet the inclusion criteria, and parents refused for 15.

Participant milestones

Participant milestones
Measure	Advil® Pediatric Drops for Infants Oral ibuprofen (Advil® Pediatric drops for infants less than 3 months of age; Wyeth-Ayerst 40 mg/ml, DIN 2242522), at a dosage of 5 mg/kg/dose. The drug was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Advil® Pediatric drops for infants: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants	Control Oral placebo: composed of sodium stearate 0.25g + lactose 0.5g + 15 ml of simple syrup, with a measured osmolarity of about 750 mosml/kg. The drug (or placebo) was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Placebo: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants
Overall Study STARTED	28	28
Overall Study COMPLETED	28	28
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cardio-respiratory Events and Inflammatory Response After Primary Immunization in Preterm Infants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Advil® Pediatric Drops for Infants n=28 Participants Oral ibuprofen (Advil® Pediatric drops for infants less than 3 months of age; Wyeth-Ayerst 40 mg/ml, DIN 2242522), at a dosage of 5 mg/kg/dose. The drug was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Advil® Pediatric drops for infants: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants	Control n=28 Participants Oral placebo: composed of sodium stearate 0.25g + lactose 0.5g + 15 ml of simple syrup, with a measured osmolarity of about 750 mosml/kg. The drug (or placebo) was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Placebo: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants	Total n=56 Participants Total of all reporting groups
Age, Continuous	27.8 weeks STANDARD_DEVIATION 1.8 • n=5 Participants	27.2 weeks STANDARD_DEVIATION 2 • n=7 Participants	27.5 weeks STANDARD_DEVIATION 1.9 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: the mean of CRE occured in the 48h after immunization minus the base line CRE : mesured 24h before immunization

Immunization with the pentavalent vaccine Diphtheria-Tetanus-Acellular pertussis-Inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-IPV-Hib) at two months of age is known to be associated with cardio-respiratory events (CRE), in 11 to 47% of preterm infants.It is considered that the immature brainstem respiratory control of preterms make them more vulnerable to the inflammatory reaction caused by immunization. We hypothesized that post-immunization CRE are correlated with inflammatory reaction. The primary objective was to examine the impact of endogenous PG inhibition on the occurrence of CRE following the first dose of pentavalent vaccine in preterm infants born \< 32 weeks gestation. Total CRE was expressed as the average number of events (desaturation + apneas + bradycardia) / 24 hours. Δ Total CRE / patient / 24 hours was defined as the difference between the average number of events / 24 hours observed before vs. after immunization for each patient.

Outcome measures

Outcome measures
Measure	Advil® Pediatric Drops for Infants n=28 Participants Oral ibuprofen (Advil® Pediatric drops for infants less than 3 months of age; Wyeth-Ayerst 40 mg/ml, DIN 2242522), at a dosage of 5 mg/kg/dose. The drug was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Advil® Pediatric drops for infants: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants	Control n=28 Participants Oral placebo: composed of sodium stearate 0.25g + lactose 0.5g + 15 ml of simple syrup, with a measured osmolarity of about 750 mosml/kg. The drug (or placebo) was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Placebo: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants
The Change in the Number of CRE (Extracted From Printed Monitoring Tracings Compared to Noted Nurses' Surveillance) Following the First Dose of Pentavalent Vaccine in Preterm Infants Born < 32 Weeks Gestation After Administration of Ibuprofen.	0.1 events/patient/24hours Standard Deviation 8	5.4 events/patient/24hours Standard Deviation 10

SECONDARY outcome

Timeframe: 72 h

The secondary objective was to identify predictive factors of occurrence of CRE in preterm infants after immunization through the analysis of their HRV. Two annotated polysomnographies were performed for all patients with an AURA PSG GRASS ambulatory and wireless system. Each polysomnography had a duration of 2.5 hours: the first was conducted on enrolment (the day before immunization), and the second was conducted 18 to 24 hours after immunization : we compared the mean of the datas of polysomnographies after to those before immunization.

Outcome measures

Outcome measures
Measure	Advil® Pediatric Drops for Infants n=28 Participants Oral ibuprofen (Advil® Pediatric drops for infants less than 3 months of age; Wyeth-Ayerst 40 mg/ml, DIN 2242522), at a dosage of 5 mg/kg/dose. The drug was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Advil® Pediatric drops for infants: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants	Control n=28 Participants Oral placebo: composed of sodium stearate 0.25g + lactose 0.5g + 15 ml of simple syrup, with a measured osmolarity of about 750 mosml/kg. The drug (or placebo) was administered 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses. Placebo: Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants
The Modifications in HRV That Can Predict the Occurrence of CRE in Preterm Infants After Immunization.	-10 msec Standard Deviation 36	-8 msec Standard Deviation 28

Adverse Events

Advil® Pediatric Drops for Infants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Anne Monique Nuyt

Sainte Justine university hospital center

Phone: 514 3454931

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place