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

NCT02726178 | Completed Phase 2 Results

• 1 other identifier: 2917
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Inflammation may depress respiration in neonates. The aim of this study was to establish a link between post-immunization inflammation and cardio-respiratory events (CRE). Methods: Randomized double-blind controlled study of infants born \<32 weeks gestation receiving the 2 months vaccine. Infants were randomized into an ibuprofen treatment group and a placebo control group. C-reactive protein (CRP) and prostaglandins E2 (PgE2) levels were assessed before and after immunization. CRE were recorded for 72 hours. Heart rate variability (HRV) was assessed by polysomnography.

Conditions

Complication Due to Immunization

Keywords

Apnea; bradycardia; immunization; inflammation; preterms

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

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

Secondary Outcomes (1)

• The Modifications in HRV That Can Predict the Occurrence of CRE in Preterm Infants After Immunization.

  72 h

Study Arms (2)

Advil® Pediatric drops for infants

EXPERIMENTAL

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.

Drug: Advil® Pediatric drops for infants

Control

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Advil® Pediatric drops for infants DRUG

Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants

Also known as: Oral Ibuprofen

Advil® Pediatric drops for infants

Placebo DRUG

Study the effect of inhibition of prostaglandins with ibuprofen vs placebo administration on cardio respiratory events in preterms infants

Also known as: Oral placebo:sodium stearate 0.25g+lactose 0.5g+15 ml syrup

Control

Eligibility Criteria

• Age: 7 Weeks+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• preterm infants less than 32 weeks of gestational age
• Postnatal age more than 7 weeks
• Informed parental consent

You may not qualify if:

• anomalies in cardiac conduction
• congenital malformations
• severe intraventricular haemorrhage (grade 3 or 4) or with periventricular leukomalacia

Sponsors & Collaborators

• St. Justine's Hospital: lead
• Rennes University Hospital: collaborator

Related Publications (2)

• Hoch B, Bernhard M. Central apnoea and endogenous prostaglandins in neonates. Acta Paediatr. 2000 Nov;89(11):1364-8. doi: 10.1080/080352500300002589.

  PMID: 11106051 BACKGROUND

• Schulzke S, Heininger U, Lucking-Famira M, Fahnenstich H. Apnoea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines. Eur J Pediatr. 2005 Jul;164(7):432-5. doi: 10.1007/s00431-005-1674-3. Epub 2005 Apr 21.

  PMID: 15843978 BACKGROUND

Related Links

• the full bibliographic citation of the article on Pubmed

MeSH Terms

Conditions

Apnea; Bradycardia; Inflammation

Interventions

Ibuprofen; Lactose

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Limitations and Caveats

1-the small number of patient recruted

Results Point of Contact

• Title: Dr. Anne Monique Nuyt
• Organization: Sainte Justine university hospital center

anne-monique.nuyt@recherche-ste-justine.qc.ca

514 3454931

Study Officials

• Anne Monique Nuyt, MD

  Ste-Justine's hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatalogist, MD

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: April 1, 2016
• Study Start: February 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: April 1, 2012
• Last Updated: May 17, 2018
• Results First Posted: June 5, 2017

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share