Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol

Felix Ines; Shandee Hutson; Katherine Coughlin; Andrew Hopper; Anamika Banerji; Cherry Uy; Neil Finer; Wade Rich; Ana Morales; Jane Steen; Anup C Katheria

doi:10.1136/bmjopen-2020-038343

Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol

BMJ Open. 2021 Jan 22;11(1):e038343. doi: 10.1136/bmjopen-2020-038343.

Authors

Affiliations

¹ Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California, USA.
² Neonatology, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California, USA.
³ Loma Linda University Medical Center, Loma Linda, California, USA.
⁴ University of California Irvine, Irvine, California, USA.
⁵ University of California San Diego, La Jolla, California, USA.
⁶ Neonatology, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California, USA anup.katheria@sharp.com.

Abstract

Introduction: Respiratory distress syndrome (RDS) or surfactant deficiency occurs primarily in premature infants resulting in composite outcomes of death or bronchopulmonary dysplasia. Initial management strategies for preterm infants with RDS includes early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen (FiO₂), and may include the use of less invasive surfactant administration (LISA) to avoid the need for mechanical ventilation. In order to optimise success of non-invasive support, the use of early caffeine therapy may be critical to the success of LISA. The objective of our trial is to evaluate whether infants that receive early caffeine, CPAP and surfactant via the LISA method compared with infants that receive caffeine and CPAP alone, have a decreased need for invasive mechanical ventilation in the first 72 hours of life.

Methods and analysis: CaLI is an unblinded multicentre, randomised controlled, trial of 180 preterm infants (24+0-29+6 weeks corrected GA). Criteria for intubation/treatment failure will follow guidelines for the management of RDS, including: (1) CPAP level of 6-8 cmH20 and FiO₂ >0.40 required to maintain saturations 90%-95% for 2 hours after randomisation; (2) a pH of 7.15 or less or a paCO₂ >65 mm Hg on any (2) blood gases (arterial/capillary/or venous) at least 2 hours after randomisation and in the first 72 hours of life; (3) continued apnoea/bradycardia/desaturation events despite nasal intermittent minute ventilation mode of ventilation. Infants will be randomised by 1 hour of life and caffeine/LISA treatments administered by 2 hour of life. Caffeine will be administered prior to surfactant in the LISA arm and before 2 hours of life in the control arm.

Ethics and dissemination: Chiesi Farmaceutici, S.p.A is the sponsor of CaLI. Ethical approval has been obtained. Results will be submitted for publication in peer reviewed journals.

Trial registration number: www.Clinicaltrials.gov: NCT04209946; Pre-results.

Keywords: neonatal intensive & critical care; neonatology; respiratory medicine (see thoracic medicine).

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Caffeine / therapeutic use
Continuous Positive Airway Pressure
Humans
Infant
Infant, Newborn
Infant, Premature
Multicenter Studies as Topic
Pulmonary Surfactants* / therapeutic use
Randomized Controlled Trials as Topic
Respiratory Distress Syndrome, Newborn* / therapy
Surface-Active Agents / therapeutic use

Substances

Pulmonary Surfactants
Surface-Active Agents
Caffeine

Associated data

ClinicalTrials.gov/NCT04209946