Non Inferiority Trial Investigating Surfactants Administered Via MIST (Niftisurf)

RESEARCH DESIGN Multicenter, randomized, controlled trial. RECRUITMENT Entry criteria Preterm infants 28-35 6/7 weeks' gestation and less than 48 hours of age who have a clinical diagnosis of respiratory distress syndrome. Infants who are on NCPAP and FiO2 ≥0.30 will randomized to curosurf or infasurf via MIST.

Exclusion criteria Infants will be excluded if there is a congenital anomaly or an alternative cause for respiratory distress.

Babies who require emergent intubation will not be enrolled in the interventions.

Parental Consent will be obtained prior to randomization.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Distress Syndrome
• Intervention / Treatment: Drug: MIST surfactant

Detailed Description

INTERVENTION Infants who on CPAP who reach the threshold of 30% oxygen will be randomized to calfactant (Infasurf), 3ml/kg or poractant alfa (Curosurf), 2.5ml/kg, administered under direct laryngoscopy using a surfactant instillation catheter (MIST) 16G Angiocath (Becton Dickinson, Sandy, UT, USA).

A second dose of calfactant (Infasurf) 3ml/kg or poractant alfa (Curosurf), 1.25ml/kg, will be administered via MIST their fiO2 reaches the threshold of 30% between 6 and 48 hours after the first dose.

No further surfactant should be given in the first 7 days unless the infant reaches the intubation criteria.

POST-INTERVENTION MANAGEMENT Other than the requirement to adhere to intubation criteria in the first week, and in some cases perform a room air trial at 36 weeks corrected gestation, management will be at the discretion of the clinical team.

Titration of CPAP pressure is encouraged, with a permitted maximum of 8 cm H2O. Use of nasal IPPV is allowable for apnea, but discouraged for RDS and should only be after at least one dose of surfactant has been given. Early caffeine therapy is expected.

Criteria for intubation:

Enrolled infants on CPAP will be intubated if:

• FiO2 ≥0.45 for 15 minutes, or if there is unremitting apnea (> 6 episodes/hour requiring intervention or in the opinion of the treating physician) or persistent respiratory acidosis (pH<7.25 and pCO2 >60) on blood gasses at least 30 minutes apart or metabolic acidosis refractory to treatment.
• Need for an anesthetic or an intervention requiring intubation

These criteria apply during the first week of life, and to the first episode of intubation only. If the infant is intubated it is expected that another dose of surfactant will be administered.

• Study Type: Interventional
• Enrollment (Estimated): 262
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Matthew Derrick; Phone Number: 18475702920; Email: mderrick@northshore.org

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Recruiting
      • Northshore University Healthsystem
      • Contact: Matthew Derrick, MBBS; Phone Number: 8475702920; Email: mderrick@northshore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Preterm infants 28-35 6/7 weeks' gestation and less than 48 hours of age who have a clinical diagnosis of respiratory distress syndrome confirmed by a chest x-ray on nasal continuous positive airway pressure (NCPAP) and FiO2 ≥0.30

Exclusion Criteria:

• Infants will be excluded if there is a congenital anomaly or an alternative cause for respiratory distress.
• Infants who require emergent intubation will not be enrolled in the interventions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calfactant (Infasurf); Neonate, 28-35 weeks gestation, less than 48 hours of age, with respiratory distress syndrome on CPAP > 30% oxygen will be given 3ml/kg of Calfacant	Drug: MIST surfactant; Surfactant will be given via MIST while neonate is on CPAP
Experimental: Poractant alfa (Curosurf); Neonate, 28-35 weeks gestation, less than 48 hours of age, with respiratory distress syndrome on CPAP > 30% oxygen will be given 2.5ml/kg of Poractant alfa.	Drug: MIST surfactant; Surfactant will be given via MIST while neonate is on CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of infants requiring Endotracheal Intubation	Infants will have an endotracheal placed if their inspired oxygen is >45% for more than 15 minutes	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of positive pressure support	Endotracheal ventilation or Non-invasive Ventilation or CPAP or NC flow>2 L	36 weeks corrected gestational age
Duration of Supplemental oxygen	Oxygen requirement to keep saturations >95%	36 weeks corrected gestational age

Collaborators and Investigators

• Sponsor: Endeavor Health

Publications and helpful links

General Publications

• Kribs A, Hartel C, Kattner E, Vochem M, Kuster H, Moller J, Muller D, Segerer H, Wieg C, Gebauer C, Nikischin W, Wense Av, Herting E, Roth B, Gopel W. Surfactant without intubation in preterm infants with respiratory distress: first multi-center data. Klin Padiatr. 2010 Jan-Feb;222(1):13-7. doi: 10.1055/s-0029-1241867. Epub 2010 Jan 18.
• Dargaville PA, Kamlin COF, Orsini F, Wang X, De Paoli AG, Kanmaz Kutman HG, Cetinkaya M, Kornhauser-Cerar L, Derrick M, Ozkan H, Hulzebos CV, Schmolzer GM, Aiyappan A, Lemyre B, Kuo S, Rajadurai VS, O'Shea J, Biniwale M, Ramanathan R, Kushnir A, Bader D, Thomas MR, Chakraborty M, Buksh MJ, Bhatia R, Sullivan CL, Shinwell ES, Dyson A, Barker DP, Kugelman A, Donovan TJ, Tauscher MK, Murthy V, Ali SKM, Yossuck P, Clark HW, Soll RF, Carlin JB, Davis PG; OPTIMIST-A Trial Investigators. Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial. JAMA. 2021 Dec 28;326(24):2478-2487. doi: 10.1001/jama.2021.21892.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: CPAP; Neonate; Pulmonary Surfactant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: EH23-232

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No