A Study To InvestigateThe Safety, Tolerability And Efficacy Of Nebulised Curosurf® In Preterm Neonates With Respiratory Distress Syndrome (RDS)

A Randomized, Open, Multinational, Multicentre,2-Part Study In Spontaneously Breathing Preterm Neonates With Mild To Moderate Respiratory Distress Syndrome (RDS) To Investigate The Safety, Tolerability And Efficacy Of Inhaled Nebulised Poractant Alfa (Porcine Surfactant, Curosurf®) In Comparison With Nasal Continuous Positive Airway Pressure (nCPAP) Alone

The present study will mainly aim at investigating the safety, tolerability and efficacy of different escalating single doses administration of nebulised Curosurf®, in preterm neonates with RDS (Respiratory Distress Syndrome) during nCPAP.

Study Overview

• Status: Terminated
• Conditions: Neonatal Respiratory Distress Syndrome
• Intervention / Treatment: Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I); Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II); Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I); Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II)

Detailed Description

The study will be conducted in spontaneously breathing preterm neonates with mild to moderate RDS and will consist of two parts:

Part I, with the objective to assess the safety and tolerability of single ascending doses of nebulised Curosurf® ; Part II, with the objective to compare the efficacy of nebulised Curosurf®, administered at two selected doses from part I, during nCPAP, versus nCPAP alone in terms of incidence of respiratory failure in the first 72 hours of life.

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Firenze, Italy, 50134
    • Prof.Carlo Dani, Coordinating Investigator - Careggi Hospital, Florence (Italy)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 7 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth
2. Inborn neonates from 28+0 to 32+6 weeks of gestational age (GA), spontaneously breathing and stabilised on nCPAP
3. Clinical course consistent with RDS.
4. Receiving CPAP pressure 5-8 centimeter of water (cm H2O) and fraction of inspired oxygen (FiO2) between 0.25 and 0.40 to maintain saturation of peripheral oxygen (SpO2) between 88% and 95% for at least 30 minutes. Randomization should occur between 60 minutes and 12 hours after birth.

Exclusion Criteria:

1. Early need for endotracheal intubation for cardiopulmonary resuscitation in delivery room or within 1 hour from birth because of severe RDS
2. Respiratory Distress not secondary to surfactant deficiency
3. Use of surfactant prior to study entry and need for endotracheal administration of any other treatment.
4. Major congenital anomalies.
5. Evidence of severe birth asphyxia
6. Mothers with prolonged rupture of the membranes
7. Presence of air leaks.
8. Presence of IVH (intraventricular hemorrhage ) ≥ III.
9. Hypotension or evidence of hemodynamic instability.
10. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk.
11. Participation in another clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: nCPAP+ Nebulised Curosurf®; Curosurf® administered through nebulization	Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I); Single ascending doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part I); Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II); Two doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part II)
OTHER: nCPAP alone (control); Standard of care, respiratory support used also during experimental arms	Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I); Nasal continuous positive airway pressure alone; Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II); nasal continuous positive airway pressure alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of neonates with respiratory failure	Respiratory failure defined as: need for endotracheal surfactant administration and/or mechanical ventilation	in the first 72 hours of life
Adverse Events	Any untoward medical occurrence in a clinical trial neonate administered a medicinal product and which does not necessarily have a casual relationship with the treatment	discharge or 36 weeks post menstrual age (PMA), whichever comes first
Adverse Drug Reactions	Any untoward and unintended responses to an investigational product related to any dose administered	discharge or 36 weeks post menstrual age (PMA), whichever comes first

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Carlo Dani, MD, Careggi Hospital, Florence (Italy)

Publications and helpful links

General Publications

• Dani C, Talosi G, Piccinno A, Ginocchio VM, Balla G, Lavizzari A, Stranak Z, Gitto E, Martinelli S, Plavka R, Krolak-Olejnik B, Lista G, Spedicato F, Ciurlia G, Santoro D, Sweet D; CURONEB Study Group. A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome. J Pediatr. 2022 Jul;246:40-47.e5. doi: 10.1016/j.jpeds.2022.02.054. Epub 2022 Mar 5.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 28, 2017
• Primary Completion (ACTUAL): May 5, 2020
• Study Completion (ACTUAL): May 5, 2020

Study Registration Dates

• First Submitted: July 26, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (ACTUAL): August 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: RDS
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hyaline Membrane Disease; Respiratory System Agents; Pulmonary Surfactants; Poractant alfa
• Other Study ID Numbers: CCD-01534CA1-01; 2016-004547-36 (EUDRACT_NUMBER)

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: No
• Studies a U.S. FDA-regulated device product: No