NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) Trial: Protocol for a Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 324
- 试验地点
- 4
- 主要终点
- LISA failure within 24 hours.
研究概览
简要总结
The NONA-LISA trial will be an investigator-initiated, multicentre, pragmatic, parallel-group, blinded RCT conducted at four university hospitals across Denmark. A total of 324 inborn premature infants will be included within 36 months at four neonatal intensive care units (NICUs) across Denmark (approximately 2 infants per month per unit).
The aim is to compare LISA using a non-pharmacological approach alone with routine analgesic treatment combined with a non-pharmacological approach (according to local guidelines) regarding LISA failure defined as the need for positive pressure ventilation for 30 min or more (cumulated) within 24 hours after the procedure in infants born prior to 30 gestational weeks.
详细描述
Background
Less Invasive Surfactant Administration (LISA) is a way of applying surfactant in the trachea by use of a catheter during spontaneous breathing and after applying nasal continuous positive airway pressure (nCPAP). However, use of pre-procedure analgesia with risk of apnoea may prevent LISA to achieve its full potential.
Aim
This study aims to compare the LISA procedure using a non-pharmacological approach to the LISA procedure using analgesic treatment with 0.5-1 mcg/kg fentanyl in infants born at 24 to 29 completed gestational weeks who fulfil the criteria for surfactant treatment.
Trial design
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participant, care provider, investigator and outcomes assessor will initially be blinded to treatment with analgesia or placebo (isotonic saline solution). Need for additional doses of analgesia will be decided according to section "Interventions" and will not be blinded. To reduce risk of interpretation bias, primary analyses will be performed blinded to the group allocation (Group A compared with Group B) and will be presented to all authors, who will agree on two alternative written interpretations before the randomisation code will be unblinded.
入排标准
- 年龄范围
- 24 Weeks 至 30 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants born at one of the trial sites with a gestational age of 24+0 to 29+6 weeks and meeting the criteria for first-choice surfactant treatment by LISA as described by Sweet et al.: worsening babies with RDS and FiO2 > 0.30 on CPAP pressure ≥6 cm H2O.
排除标准
- •suspicion of lung hypoplasia,
- •endotracheal intubation at any time before randomisation,
- •suspicion of pneumothorax, pulmonary haemorrhage or pleural effusion before LISA,
- •major congenital anatomical anomalies as described by the European Surveillance of Congenital Anomalies (EUROCAT).
研究组 & 干预措施
Fentanyl group
Patients will receive 0.5-1 mcg/kg fentanyl intravenously as pre-procedure analgesia for Less Invasive Surfactant Administration (LISA).
The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.
干预措施: Less Invasive Surfactant Administration (LISA) (Procedure)
Fentanyl group
Patients will receive 0.5-1 mcg/kg fentanyl intravenously as pre-procedure analgesia for Less Invasive Surfactant Administration (LISA).
The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.
干预措施: Fentanyl (Drug)
Saline group
Patients will receive a placebo (isotonic saline) instead of pre-procedure analgesia for Less Invasive Surfactant Administration (LISA).
The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.
干预措施: Less Invasive Surfactant Administration (LISA) (Procedure)
Fentanyl group
Patients will receive 0.5-1 mcg/kg fentanyl intravenously as pre-procedure analgesia for Less Invasive Surfactant Administration (LISA).
The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.
干预措施: Non-pharmacological standard operating procedure (Behavioral)
Saline group
Patients will receive a placebo (isotonic saline) instead of pre-procedure analgesia for Less Invasive Surfactant Administration (LISA).
The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.
干预措施: Isotonic saline (Drug)
Saline group
Patients will receive a placebo (isotonic saline) instead of pre-procedure analgesia for Less Invasive Surfactant Administration (LISA).
The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.
干预措施: Non-pharmacological standard operating procedure (Behavioral)
结局指标
主要结局
LISA failure within 24 hours.
时间窗: 24 hours after procedure.
The primary outcome will be LISA failure in terms of the need for endotracheal intubation and mechanical ventilation for at least 30 minutes (cumulated) within 24 hours after the procedure.
次要结局
- Cumulated duration of oxygen treatment with fraction of inspired oxygen (FiO2) >0.21.(Before discharge (through study completion, an average of 6 months).)
- Observed surfactant reflux(24 hours after procedure.)
- Need for a second dose of surfactant(24 hours after procedure.)
- Desaturation with SaO2 (right extremity measure) <85% during the procedure(24 hours after procedure.)
- Procedural time consumption from the introduction of the laryngoscope blade into the oral cavity to removal of the catheter.(24 hours after procedure.)
- Number of attempts of insertion of the catheter in the trachea.(24 hours after procedure.)
- Cumulated duration of positive pressure ventilation during hospitalisation.(Before discharge (through study completion, an average of 6 months).)
- Incidence of additional fentanyl administration(During the procedure, an average of 5-10 minutes.)
- Pain or discomfort during the procedure (according to COMFORTneo score >14).(24 hours after procedure)
- Escalation from LISA to INSURE in the same attempt(24 hours after procedure.)
- Apnoea that require bag and mask ventilation during the procedure(24 hours after procedure.)
- Number of attempts of insertion of the laryngoscope in the oral cavity.(24 hours after procedure.)
- Incidence of endotracheal intubation.(48 hours after procedure)
- Incidence of massive pulmonary haemorrhage within 48 hours after LISA (defined as the aspiration of haemorrhagic secretions from the trachea concurrent with the need for escalated respiratory support).(48 hours after procedure.)
- Incidence of in-hospital mortality before discharge.(Through study completion, an average of 6 months.)
- Incidence of escalation of respiratory support from CPAP to other NIV modes during hospitalisation.(Before discharge (through study completion, an average of 6 months).)
- Incidence of necrotising enterocolitis (according to Bell's Staging Criteria).(Before discharge (through study completion, an average of 6 months).)
- Time from meeting the criteria for surfactant treatment until surfactant administration(24 hours after procedure.)
- Incidence of pneumothorax within 48 hours after LISA.(48 hours after procedure.)
- Cumulated duration of any repisratory support during hospitalisation.(Before discharge (through study completion, an average of 6 months).)
- Incidence of intraventricular haemorrhage grade 3-4 and periventricular leukomalacia.(Before discharge (through study completion, an average of 6 months).)
- Bradycardia <100 BPM for a minimum duration of 4 seconds.(24 hours after procedure.)
- Cumulated duration of mechanical ventilation during hospitalisation.(Before discharge (through study completion, an average of 6 months).)
- Cumulated duration of all types of non-invasive respiratory support during hospitalisation.(Before discharge (through study completion, an average of 6 months).)
- Duration of hospitalisation.(Before discharge (through study completion, an average of 6 months).)
- Incidence of treatment-demanding retinopathy of prematurity.(Before discharge (through study completion, an average of 6 months).)
- Composite outcome of death or moderate/severe BPD at 36 weeks of corrected gestational age.(36 weeks of corrected gestational age.)
研究者
Lise Aunsholt
MD, PhD, associate professor
Rigshospitalet, Denmark