Clinical trial NCT02452476: A Double Blind, Randomized, Controlled Study to Evaluate CHF 5633 (Synthetic Surfactant) and Poractant Alfa in Neonates With Respiratory Distress Syndrome (RDS) (POC)
Official title: A DOUBLE BLIND, RANDOMIZED, CONTROLLED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF SYNTHETIC SURFACTANT (CHF 5633) IN COMPARISON TO PORCINE SURFACTANT (PORACTANT ALFA, CUROSURF®) IN THE TREATMENT OF PRETERM NEONATES WITH RESPIRATORY DISTRESS SYNDROME
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Distress Syndrome, Newborn
Keywords: neonates, pulmonary surfactant
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2015-05-22
Enrollment: 123
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multicenter, double blind, randomized, single dose, active-controlled study to investigate the efficacy and safety of synthetic surfactant (CHF 5633) in comparison to porcine surfactant (Poractant alfa, Curosurf ®) in the treatment of preterm neonates with respiratory distress syndrome. Main objectives of this study are to investigate the short term efficacy profile of CHF 5633 vs. porcine surfactant (Poractant Alfa, Curosurf®) in terms of reduced oxygen requirement and ventilatory support and to evaluate the mid-term efficacy profile in terms of reduced incidence of bronchopulmonary dysplasia (BPD) and mortality/BPD rate at 36 weeks post menstrual age (PMA), mortality rate at 28 days and 36 weeks PMA, RDS-associated mortality through 14 days of age and other major co-morbidities of prematurity.

Inclusion criteria are: Written parental informed consent, inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks, clinical course consistent with RDS, requirement of endotracheal surfactant administration within 24 hours from birth, fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain arterial oxygen saturation by pulse oximetry (SpO2) between 88-95%.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to any study-related procedures
2. Inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks
3. Clinical course consistent with RDS
4. Requirement of endotracheal surfactant administration within 24 hours from birth
5. Fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain SpO2 between 88-95%

Exclusion Criteria:

1. Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
2. Known genetic or chromosomal disorders, major congenital anomalies (cardiac malformations, myelomeningocele etc)
3. Maternal drug abuse (heroin, methadone, methamphetamine, or cocaine) or significant alcohol consumption during pregnancy
4. Mothers with prolonged rupture of the membranes (\>21 days duration)
5. Strong suspicion of congenital pneumonia/infection, sepsis
6. Presence of air leaks prior to study entry
7. Evidence of severe birth asphyxia
8. Neonatal seizures prior to study entry
9. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
10. Participation in another clinical trial of any placebo, drug or biological substance conducted under the provisions of a protocol.

Primary outcomes:
measure: Oxygen Requirement and Ventilatory Support -- SpO2/FiO2 Ratio
timeFrame: Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7
measure: Fraction of Inspired Oxygen (FiO2) (Percent) During the First 24 h and up to Day 7
timeFrame: Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7
measure: Number of Patients With Bronchopulmonary Dysplasia and Mortality
timeFrame: 36 weeks post menstrual age, Day 14 Post-Natal Age, Day 28 Post-Natal Age
Secondary outcomes:
Other outcomes:
measure: Number of Patients With Normal Breathing (Room Air) Within 24 Hours
timeFrame: Post-treatment up to 24 h
measure: Number of Patients With the Need for Re-dosing (Use of Rescue Surfactant)
timeFrame: Day 1 to Day 7
measure: Time to Reach Normal Breathing (Room Air) Within 24 Hours
timeFrame: Post-treatment Day 1: up to 24 h
measure: Concentration of Biomarkers of Inflammation in Tracheal Aspirates
timeFrame: Post-treatment Day 1 (24 h), Day 2 (48 h)
measure: Immunogenicity: Assessment of Antibodies to Surfactant Protein B (SP-B) Analogue (CHF 5736.03) and to Surfactant Protein C (SP-C) Analogue (CHF 4902.03)
timeFrame: At approximately 5 weeks after the administration of study drug (with a range from 3 to 6 weeks).
Locations:
city: Mobile
country: United States
facility: University of South Alabama - USA Children's and Women's Hospital
state: Alabama
city: Los Angeles
country: United States
facility: LAC + USC Medical Center, Keck School of Medicine
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Plantation
country: United States
facility: Plantation General Hospital (Sheridan Clinical Research, Inc.)
state: Florida
city: Augusta
country: United States
facility: Jatinder Bhatia
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Louisville
country: United States
facility: University of Louisville Research Foundation, Inc.
state: Kentucky
city: Boston
country: United States
facility: Floating Hospital for Children at Tufts Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Children's Hospital / Baystate Medical Center
state: Massachusetts
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Kings County Hospital Center
state: New York
city: Valhalla
country: United States
facility: Sergio G. Golombek
state: New York
city: Greenville
country: United States
facility: Martha Naylor
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Oklahoma City
country: United States
facility: Krishnamurthy Sekar
state: Oklahoma
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Good Samaritan Hospital, Keck School of Medicine of USC, Los Angeles, CA, USA
name: Rangasamy Ramanathan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramanathan R, Biniwale M, Sekar K, Hanna N, Golombek S, Bhatia J, Naylor M, Fabbri L, Varoli G, Santoro D, Del Buono D, Piccinno A, Dammann CE. Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial. J Pediatr. 2020 Oct;225:90-96.e1. doi: 10.1016/j.jpeds.2020.06.024. Epub 2020 Jun 14.