Cardio-respiratory Events and Inflammatory Response After Primary Immunization in Preterm Infants < 32 Weeks Gestational Age: A Randomized Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
Background: 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), such as apnea and bradycardia, in 11 to 47% of preterm infants [1,2]
Methods: This randomized, double blinded, placebo-controlled study was conducted in the neonatal intensive care unit of Sainte-Justine University Hospital (Montreal, QC, Canada) over a period of fourteen months (February 2010 - March 2011). Study was approved by CHU Sainte-Justine institutional Ethics Committee for Clinical Studies. Written informed parental consent was obtained for all infants.
The vaccines administered were: Diphtheria-Tetanus-Acellular pertussis-Inactivated polio-Haemophilus influenzae type B (DTaP-IPV-HIB: Pediacel® 0.5ml) and the pneumococcal conjugate 10-valent vaccine (Synflorix® 0.5ml). The two vaccines were administered by nurses intramuscularly in the anterolateral region of each thigh.
On enrollment, patients were randomized by the pharmacy (investigator blinded) into two groups: the study group received oral ibuprofen (Advil® Pediatric drops for infants < 3 months of age; Wyeth-Ayerst 40 mg/ml, DIN 2242522) 5 mg/kg/dose as recommended by the manufacturer (Ibuprofen; n=28):http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails.
The control group received an oral placebo (Placebo; n=28). The placebo was prepared by the CHU Sainte-Justine pharmacy and was composed of sodium stearate 0.25g + lactose 0.5g + 15 ml of simple syrup, with a measured osmolarity of about 750 mosml/kg. The drugs were administered by nurses in an opaque syringe 30 minutes prior to immunization, and then at 8 and 16 hours following the immunization for a total of 3 doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •preterm infants less than 32 weeks of gestational age
- •Postnatal age more than 7 weeks
- •Informed parental consent
排除标准
- •anomalies in cardiac conduction
- •congenital malformations
- •severe intraventricular haemorrhage (grade 3 or 4) or with periventricular leukomalacia
研究组 & 干预措施
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.
干预措施: Advil® Pediatric drops for infants (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- The Modifications in HRV That Can Predict the Occurrence of CRE in Preterm Infants After Immunization.(72 h)
研究者
Anne-Monique NUYT
Neonatalogist, MD
St. Justine's Hospital