A Prospective, Randomized, Open-label Clinical Trial to Assess Apnea Following Administration of 13-valent Conjugate Pneumococcal Vaccine, Diphtheria Toxoid, Tetanus Toxoid, and Acellular Pertussis Vaccine, Inactivated Polio Vaccine, Hepatitis B Vaccine, and Haemophilus Influenzae Type B Vaccine in Preterm Infants
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 223
- 试验地点
- 8
- 主要终点
- Occurrence of Apnea
研究概览
简要总结
A prospective, randomized open-label clinical trial will be conducted from July 2018 to October 2020. Approximately 300 preterm infants will be enrolled across three sites: Duke University Medical Center, the University of North Carolina, and Cincinnati Children's Hospital Medical Center. Eligible infants will be randomized 1:1 to receive either 2-month US licensed childhood vaccines (PCV13, DTaP, HBV, IPV an Hib) or no vaccines. After their participation in the study, healthcare providers of the infants in the unvaccinated group will make decision abut receipt of their 2-month childhood vaccines. The study will collect data from the continuous cardiorespiratory and pulse oximetry monitors from randomization to 48 hours after randomization for infants in the unvaccinated group, and from randomization to 48 hours after vaccination for infants in the vaccinated group. Infants in both groups will be monitored for up to 60 hours for the occurrence of apnea, bradycardia, and oxygen desaturation. For infants in the "vaccinated" group, the study will also collect adverse events of clinical interest and serious adverse events occurring between the end of the 48-hour monitoring period and 14 days after vaccination. This information will be collected through parental report and review of medical records.
详细描述
Modified Intent-to-Treat (mITT) Analysis Population: Defined as any infant that was enrolled and randomized in the study
For the mITT analysis, infants will be analyzed in their assigned treatment arms irrespective of receipt of vaccine. Study outcomes will be included in the analysis as follows:
i) Vaccinated group: study outcomes in the 48-hour monitoring after vaccination. If vaccination does not occur by 12 hours after randomization, then study outcomes will be assessed between 12 and 60 hours after randomization.
ii) Unvaccinated group: study outcomes in the 48-hour monitoring period after randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 6 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •<33 and 0 days weeks gestational age at birth
- •≥6 weeks and 0 days and ≤12 weeks and 0 days postnatal age at randomization
- •Remains hospitalized after birth (has never been discharged home)
- •Treating clinician deems infant eligible to receive 2-month vaccines
- •English- or Spanish-speaking parent(s)/legally authorized representative(s) (LAR(s))
- •Not planned for discharge within 60 hours of study entry
- •The parent/guardian must be willing and capable of providing permission for their child to participate through the written informed consent process
排除标准
- •Receipt of DTaP, IPV, PCV13, or Hib prior to enrollment. Previous administration of the first dose of HBV is permitted
- •Anticipated receipt of any vaccine other than DTaP, IPV, HBV, PCV13, or Hib during the first 60 hours after randomization
- •History of a severe allergic reaction (e.g. anaphylaxis) to a previous dose of any hepatitis B vaccine
- •History of a severe allergic reaction (e.g. anaphylaxis) to any component of the vaccines used in the study including neomycin, yeast and polymyxin B
- •History of latex allergy
- •Fever ≥38°C within 48 hours prior to randomization*
- •*This may result in a temporary delay of randomization
- •Active known respiratory infection within 48 hours prior to randomization*
- •*This may result in a temporary delay of randomization
- •Active infection being treated with systemic antimicrobials*
- •*This may result in a temporary delay of randomization
- •Requiring mechanical ventilation or support with nasal intermittent positive pressure ventilation (NIPPV)*
- •*This may result in a temporary delay of randomization
- •History of unstable progressive neurologic disorder of unknown cause
- •Known cause of apnea other than apnea of prematurity
- •Cyanotic heart disease (congenital or acquired)
- •Major invasive medical or surgical procedure (including circumcision) within 48 hours prior to randomization or anticipated to have major invasive medical or surgical procedure during the first 60 hours after randomization*
- •*This may result in a temporary delay of randomization
- •Child or parent/LAR is an immediate relative of study staff or an employee who is supervised by study staff.
- •Any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
结局指标
主要结局
Occurrence of Apnea
时间窗: 48 hours
Number of infants with ≥ 1 apneic event in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group, mITT Population Apnea was defined as a pause in respirations of \>20 seconds, or a pause in respirations of \>15 seconds with associated bradycardia (heart rate \<80 beats per minute for any duration occurring within 1 minute of the apnea event). Potential apnea events triggered by the cardiorespiratory monitors were manually reviewed by 2 neonatologists to verify the event. In uncommon situations in which manual review of a triggered event was not possible due to missing data, the triggered event was considered to be apnea.
次要结局
- Number of Apneic Episodes(48 hours)
- Duration of Apneic Episodes(48 hours)
- Increase in Respiratory Support(48 hours)
- Severe Cardiorespiratory Events(48 hours)
- Positive Pressure Ventilation(48 hours)