Premedication for Less Invasive Surfactant Administration

Surfactant Deficiency Syndrome Neonatal Clinical Trial

— LISA-Med  

Official title:

Premedication for Less Invasive Surfactant Administration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03735563
• Other study ID #: OY062018
• Status: Recruiting
• Phase: Phase 4
• Start date: February 11, 2019
• Est. completion date: October 31, 2026

Study information

• Verified date: June 2023
• Source: University of Oulu
• Contact: Eveliina Ronkainen, MD, PhD
• Phone: +358 8 3152011
• Email: eveliina.ronkainen[@]oulu.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Early respiratory management of preterm infants immediately after birth should be as gentle as possible. With this so-called developmental approach, unnecessary invasive methods can be avoided or at least postponed. This kind of "soft landing" allows cardiorespiratory transition with fewer adverse outcomes. Less invasive surfactant administration (LISA) is a technique that involves delivery of surfactant to a spontaneously breathing infant through a thin catheter. This technique minimizes the risk for neonatal lung injury caused by positive pressure ventilation. LISA is nowadays widely used in neonatal intensive care units (NICU). Although less invasive, newborns exposed to this procedure need premedication prior the procedure. There is no consensus, which drug would be the optimal premedication for LISA and the research on this topic is lacking. An ideal premedication would treat the procedural pain without suppressing the infant's own breathing. The sedation and analgesia should start fast but the effect should be short-acting with as few adverse effects as possible. The aim of this randomized, controlled trial (RCT) is to evaluate the feasibility, efficacy and safety of LISA protocol with the premedication of either ketamine or fentanyl by investigating whether one or the other is associated with lower rate of adverse events, hence would be preferred choice for premedication protocol.

Description:

All infants fulfilling the inclusion criteria during the study period are asked to participate in this randomized controlled trial of LISA premedication. Written informed parental consent is acquired from all of the participants. After the consent, individuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. The investigators and medical staff are blinded to the fact which study medication is given. This study is a pilot study and 20 patients are recruited for both groups. Randomization is done in the blocks of four. S-ketamine (Ketanest-S 5 mg/ml) or fentanyl (Fentanyl-Hamel diluted to 5 μg/ml) is used as a masked study drug. Both study drug solutions appear equally transparent. Drug administration is started with glucopyrrolate (Robinul 0.2 mg/ml), which is given intravenously at a dose of 5 µg/kg. Thereafter, the masked study drug is administered intravenously slowly in one to two minute injection of 0.2 ml/kg. In this way, doses of S-ketamine 1 mg/kg or alternatively fentanyl 1 μg/kg is received. After five minutes (from the beginning of administration of the study drug), videolaryngoscopy is started. If the study drug does not have sufficient effect, the study drug may be repeated with the same dose. If study drug fails to give appropriate conditions to LISA procedure, midazolam 0,1 mg/kg can be used as an additional drug.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Gestational age at birth =26 weeks
• Respiratory insufficiency managed with non-invasive respiratory support (nasal continuous positive airway pressure or high-flow)
• Requirement for oxygen to maintain oxygen saturation in the target range and need for surfactant treatment (according to clinician's assessment)
• If further doses of surfactant are needed, patient can be re-randomized

Exclusion Criteria:

• Severe RDS with high oxygen requirements, severe respiratory acidosis and/or widespread atelectasis radiologically, such that ongoing ventilator support will be necessary after surfactant therapy (intubation in preferable to LISA if FiO2 >40% at GA <28 weeks and >60% at GA =28 weeks)
• Maxillo-facial, tracheal or known pulmonary malformations
• Any known chromosomal abnormality or severe malformation
• An alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia)

Related Conditions & MeSH terms

• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Surfactant Deficiency Syndrome Neonatal

Intervention

Drug:
• Ketamine
Individuals will receive randomly either ketamine or fentanyl as a premedication
• Fentanyl
Individuals will receive randomly either ketamine or fentanyl as a premedication

Locations

Country	Name	City	State
Finland	Oulu University Hospital	Oulu

Sponsors (2)

Lead Sponsor	Collaborator
University of Oulu	Oulu University Hospital

Country where clinical trial is conducted

Finland, 

References & Publications (3)

Polkki T, Korhonen A, Axelin A, Saarela T, Laukkala H. Development and preliminary validation of the Neonatal Infant Acute Pain Assessment Scale (NIAPAS). Int J Nurs Stud. 2014 Dec;51(12):1585-94. doi: 10.1016/j.ijnurstu.2014.04.001. Epub 2014 Apr 18. — View Citation

Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111(2):107-125. doi: 10.1159/000448985. Epub 2016 Sep 21. — View Citation

Vento M, Dargaville P, Bohlin K, Herting E & Roehr C LISA Training Advisory Board Report.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse event	The need of positive pressure ventilation (PPV), intubation, heart rate below 80 per minute, mean arterial pressure change more than 20%, pH change more than 0.4, and CO2 change more than 20%, and saturation <85 for more than 1 minute	1 hour
Secondary	Duration of the procedure	Duration of the procedure is evaluated retrospectively from the recording of the videolaryngoscopy (an attempt begins when the laryngoscope enters the mouth and ends with LISACath in the trachea)	1 hour
Secondary	Number of attempts to get the catether intratracheally	Number of attempts to get the catether intratracheally is evaluated retrospectively from the recording of the videolaryngoscopy (one laryngoscopy = one attempt)	1 hour
Secondary	Pain score NIAPAS	Pain will be scored with validated Neonatal Infant Acute Pain Assessment Scale (NIAPAS) tool. The scale includes five behavioral and three physiological indicators, and takes into account the gestational age of neonates as a contextual factor. The indicators are rated on a 2, 3, or 4-point scale for a possible total score of 18. Assessments of each neonate include alertness, facial expressions, crying, muscle tension, reaction to handling, and breathing. In addition, the neonates on monitors are assessed for changes in heart rate and oxygen saturation (Copyright Pölkki T, Korhonen A, Axelin A. 2013)	1 hour
Secondary	The need for additional dosing of study drug or midazolam (number of addtional dosages)	If the study drug does not have sufficient effect, the study drug may be repeated with the same dose. If study drug fails to give appropriate conditions to LISA procedure, midazolam 0,1 mg/kg can be used as an additional drug.	1 hour
Secondary	Edi-signals	Special Edi (Electronic Diaphragm Monitoring) Catheter is placed to read the electrical activity of the diaphragm. Edi min and Edi max in different time points will be collected.	1 hour