Premedication for Less Invasive Surfactant Administration

NCT ID: NCT03735563

Last Updated: 2023-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-11
• Study Completion Date: 2026-10-31

Brief 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.

Detailed 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.

Conditions

Surfactant Deficiency Syndrome Neonatal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

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.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Individuals will receive randomly either ketamine or fentanyl as a premedication

Fentanyl

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.

Group Type: EXPERIMENTAL

Fentanyl

Intervention Type: DRUG

Individuals will receive randomly either ketamine or fentanyl as a premedication

Interventions

Ketamine

Individuals will receive randomly either ketamine or fentanyl as a premedication

Intervention Type: DRUG

Fentanyl

Individuals will receive randomly either ketamine or fentanyl as a premedication

Intervention Type: DRUG

Other Intervention Names

Ketanest-S; Fentanyl-Hamel

Eligibility Criteria

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)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oulu University Hospital

OTHER

Sponsor Role: collaborator

University of Oulu

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Riitta Marttila, MD, docent

Role: PRINCIPAL_INVESTIGATOR

Oulu University and Oulu University Hospital

Locations

Oulu University Hospital

Oulu, , Finland

Site Status: RECRUITING

Countries

Finland

Central Contacts

Eveliina Ronkainen, MD, PhD

Role: CONTACT

eveliina.ronkainen@oulu.fi

+358 8 3152011

Antti Härmä, MD

Role: CONTACT

aharma@paju.oulu.fi

+358 8 3152011

Facility Contacts

Eveliina Ronkainen, MD, PhD

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 27649091 (View on PubMed)

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 24815773 (View on PubMed)

Other Identifiers

OY062018

Identifier Type: -

Identifier Source: org_study_id