Stress Assessment in Preterm Infants With Respiratory Distress Syndrome Treated or Not With an Analgesic Drug During the Traditional or the Less Invasive Method of Surfactant Therapy.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 80
- 主要终点
- Cortisol concentrations
研究概览
简要总结
This study will compare stress, changes in oxygenation and oxidative damage in preterm infants with respiratory distress syndrome (RDS) randomized to receive or not remifentanil as an analgesic drug during the administration of porcine surfactant (poractant alfa, Curosurf®) through the traditional (INSURE) or the less invasive (LISA) method.
详细描述
At present, LISA and INSURE are both used for surfactant therapy in infants as comparable methods. However, a clear policy of using analgesics during surfactant therapy is still lacking: some neonatologists use analgesics to reduce stress and pain scores, whereas others do not approve their use due to interference with spontaneous breathing.
In this open-label, randomized, phase 4 clinical trial, infants admitted to our neonatal intensive unit care (NICU) will be evaluated according to the selection criteria and then randomized to receive or not remifentanil as an analgesic drug during the administration of porcine surfactant (poractant alfa, Curosurf®) via the INSURE or LISA method: Group-1) LISA-analgesic; Group 2) LISA-no analgesic; Group-3) INSURE-analgesic; Group-4) INSURE-no analgesic. Study patients will be stratified by gestational age at birth: Block A) 23.0-27.6 weeks of gestation; Block B) 28.0-31.6 weeks of gestation.
Early caffeine administration will be provided according to our NICU guidelines shortly after birth. Infants with adequate respiratory drive will be stabilized on nasal continuous positive airway pressure (CPAP; 4-8 cm of water) right after birth. Oxygen saturation targets will be 90-94%; moderate degrees of hypercarbia (PaCO2 < 60 mmHg, provided arterial pH >7.22) will be tolerated. Conditions mimicking respiratory distress syndrome (RDS; i.e. sepsis, air leaks, aspiration pneumonia, congenital heart disease) will be ruled out. RDS diagnosis will be clinical according to the European Guidelines. Nasal CPAP, bi-level CPAP or nasal intermittent positive pressure ventilation (synchronized or not) will be used at the discretion of the attending physician to stabilize the patients. Intubation criteria according to our NICU guidelines will be:
- severe acidosis (defined as arterial pH<7.20 with a partial pressure of carbon dioxide (PaCO2) > 55 mmHg and partial pressure of oxygen (PaO2) < 50 mmHg) with a fraction of inspired oxygen (FiO2) > 0.50;
- severe apnoea.
Enrolled infants will be evaluated from birth to day 7 of the hospital stay.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Participants and data analyst will be masked.
入排标准
- 年龄范围
- 168 Days 至 223 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •gestational age at birth between 168 and 223 days,
- •respiratory distress syndrome (diagnosed on the basis of clinical and/or radiological grounds) with a fraction of inspired oxygen ≥0.30 (for infants born ≤26 weeks' gestational age) or ≥0.40 (for infants born >26 weeks' gestational age) to achieve a peripheral oxygen saturation of 90-94% within 24 hours of life and good respiratory drive,
- •written informed consent.
排除标准
- •major malformations,
- •late admission (after 24 hours of life),
- •intubation in the delivery room,
- •severe birth asphyxia,
- •prolonged rupture of membranes,
- •air leaks,
- •no informed consent.
研究组 & 干预措施
LISA-analgesic
Less Invasive Surfactant Administration (LISA) with remifentanil (0.5-2 micrograms/kg/dose) as the analgesic drug.
干预措施: LISA (Procedure)
LISA-analgesic
Less Invasive Surfactant Administration (LISA) with remifentanil (0.5-2 micrograms/kg/dose) as the analgesic drug.
干预措施: Analgesic, Opioid (Drug)
LISA-no analgesic
Less Invasive Surfactant Administration (LISA) without an analgesic drug.
干预措施: LISA (Procedure)
INSURE-analgesic
INtubation-SURfactant-Extubation (INSURE) with remifentanil (0.5-2 micrograms/kg/dose) as the analgesic drug.
干预措施: INSURE (Procedure)
INSURE-analgesic
INtubation-SURfactant-Extubation (INSURE) with remifentanil (0.5-2 micrograms/kg/dose) as the analgesic drug.
干预措施: Analgesic, Opioid (Drug)
INSURE-no analgesic
INSURE without an analgesic drug.
干预措施: INSURE (Procedure)
结局指标
主要结局
Cortisol concentrations
时间窗: At 1, 3, 6 12, 24 hours after surfactant administration and then daily in the first week at the same time of the day (to avoid circadian variations).
Cortisol concentrations will be assessed in saliva, as salivary cortisol levels have been shown to be useful surrogate markers for plasma cortisol levels in neonates. Saliva samples will be collected using an absorbent swab stick, centrifuged at 4000 rpm for 10 minutes and kept at -80°C until assayed (minimum sample volume 25 µl). Enzyme immunoassay (ELISA kit) will be used. Basal samples will be obtained at the hospital admission and right before surfactant.
次要结局
- Heart rate(6 hours before and after surfactant therapy will be analyzed.)
- Brain oxygenation(From the hospital admission to day 7 of the hospital stay.)
- Galvanic Skin Responses(At 1, 3, 6 12, 24 hours after surfactant administration and then daily in the first week at the same time of the day (to avoid circadian variations).)
- Oxygen saturation (SpO2)(From the hospital admission to day 7 of the hospital stay.)
- Markers of oxidative stress(At the hospital admission and at 6 and 12 hours after surfactant therapy.)
研究者
Virgilio Paolo Carnielli
Director of Neonatology
Ospedali Riuniti Ancona