Clinical trial NCT02772081: A Study in Preterm Neonates With Respiratory Distress Syndrome (RDS) Comparing CUROSURF® Administration Through Less Invasive Surfactant Administration (LISA) and Conventional Administration
Official title: An Open-Label, Multicenter, Randomized, Controlled Study in Spontaneously Breathing Preterm Neonates With Respiratory Distress Syndrome to Compare Two Procedures for Porcine Surfactant (Poractant Alfa, CUROSURF®) Administration: A Less Invasive Method (LISA) During Non-invasive Ventilation (NIV) and the Conventional Administration During Brief Invasive Ventilation.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Respiratory Distress Syndrome (RDS)
Keywords: Less Invasive Surfactant administration
LISPAP
Neonates
Newborns
Respiratory Distress Syndrome (RDS)
CUROSURF®
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2016-05-13
Enrollment: 33
Sex: ALL
Minimum age (years): 30
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compared the administration of porcine surfactant (poractant alfa, Curosurf®) through a less invasive method (LISA), using a thin catheter, CHF 6440 (LISACATH®), during non-invasive ventilation (CPAP, NIPPV, BiPAP) with an approved conventional surfactant administration during invasive ventilation followed by rapid extubation in terms of short term and mid-term safety and efficacy in spontaneously breathing preterm neonates who have clinical signs of respiratory distress syndrome (RDS).

Detailed description: This study was an open-label, multicentre, randomized, controlled study of spontaneously breathing neonates with RDS. Neonates were evaluated according to the selection criteria and then randomized to surfactant treatment via LISA or standard administration procedure. The enrolment was staggered: the gestational age was restricted to 27+0 weeks up to 28+6 weeks for the first 15 neonates. Provided no safety concerns were raised, the enrolment was planned to be extended to the whole population (i.e. 25+0 weeks up to 28+6 weeks). Enrolled neonates were evaluated in a main phase of the trial until discharge or 40 weeks post-menstrual age (PMA), whichever came first. Their clinical status and neurodevelopment was to be assessed at 24-month corrected age as a separate stand-alone visit.

The Sponsor decided to terminate the study early, due to uncertain sufficient availability of the CHF 6440 catheter.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth
2. Preterm neonates of either sex aged ≥30 minutes and \<24 hours, spontaneously breathing and stabilized on non-invasive ventilation (NIV).
3. Gestational age of 25+0 weeks up to 28+6 completed weeks, except for the first 15 enrolled neonates in which the gestational age will be restricted to 27+0 weeks up to 28+6 weeks.
4. Clinical course consistent with RDS.
5. Fraction of inspired oxygen (FiO2) ≥0.30 to maintain preductal oxygen saturation (SpO2) between 88-95%.

Exclusion Criteria:

1. Need for immediate endotracheal intubation for cardiopulmonary resuscitation or insufficient respiratory drive
2. Use of nasal high frequency oscillatory ventilation (nHFOV) prior to study entry
3. Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
4. Known genetic or chromosomal disorders, major congenital anomalies (congenital heart diseases, myelomeningocele etc)
5. Mothers with prolonged rupture of the membranes (\> 21 days duration)
6. Presence of air leaks if identified and known prior to study entry
7. Evidence of severe birth asphyxia (e.g. continued need for resuscitation at 10 minutes after birth, altered neurological state, or neonatal encephalopathy)
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 medicinal product, placebo, experimental medical device, or biological substance conducted under the provisions of a protocol on the same therapeutic target.

Primary outcomes:
measure: Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment
timeFrame: First 72 hours of life.
measure: Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube
timeFrame: At first surfactant administration, up to Day 1.
measure: Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization
timeFrame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
measure: Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion
timeFrame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
measure: Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion)
timeFrame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
measure: Safety: Study Treatment Administration: Duration of Surfactant Administration
timeFrame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
measure: Safety: Study Treatment Administration: Duration of the Whole Procedure
timeFrame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Secondary outcomes:
measure: Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV)
timeFrame: First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks Post-Menstrual Age (PMA).
measure: Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant
timeFrame: First 72 hours of life.
measure: Efficacy: Neonates Needing Additional Surfactant Doses
timeFrame: First 72 hours of life.
measure: Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio
timeFrame: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.
measure: Efficacy: Fraction of Inspired Oxygen (FiO2)
timeFrame: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.
measure: Efficacy: Preductal Oxygen Saturation (SpO2)
timeFrame: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.
measure: Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period
timeFrame: First 72 hours of life, up to 28 days post-natal age (PNA), Up to 36 weeks Post-menstrual age (PMA)
measure: Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study
timeFrame: Up to 28 days PNA, Up to 36 weeks PMA
measure: Efficacy: Duration of Invasive Mechanical Ventilation During the Study
timeFrame: First 72 hours of life
measure: Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study
timeFrame: First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks PMA
measure: Efficacy: Blood Gas Analysis Parameters -- pH
timeFrame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
measure: Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2)
timeFrame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
measure: Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2)
timeFrame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
measure: Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-)
timeFrame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
measure: Efficacy: Blood Analysis Parameter -- Base Excess
timeFrame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
measure: Efficacy: Blood Analysis Parameter -- Lactate
timeFrame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Chiesi Clinical Trial Site 84029
state: Arkansas
city: Los Angeles
country: United States
facility: Chiesi Clinical Trial Site 84001
state: California
city: Los Angeles
country: United States
facility: Chiesi Clinical Trial Site 84002
state: California
city: Denver
country: United States
facility: Chiesi Clinical Trial Site 84013
state: Colorado
city: New Britain
country: United States
facility: Chiesi Clinical Trial Site 84026
state: Connecticut
city: Evanston
country: United States
facility: Chiesi Clinical Trial Site 84003
state: Illinois
city: Peoria
country: United States
facility: Chiesi Clinical Trial Site 84021
state: Illinois
city: Lexington
country: United States
facility: Chiesi Clinical Trial Site 84023
state: Kentucky
city: Springfield
country: United States
facility: Chiesi Clinical Trial Site 84028
state: Massachusetts
city: Worcester
country: United States
facility: Chiesi Clinical Trial Site 84005
state: Massachusetts
city: Lansing
country: United States
facility: Chiesi Clinical Trial Site 84008
state: Michigan
city: Saint Louis
country: United States
facility: Chiesi Clinical Trial Site 84004
state: Missouri
city: Camden
country: United States
facility: Chiesi Clinical Trial Site 84012
state: New Jersey
city: Manhasset
country: United States
facility: Chiesi Clinical Trial Site 84024
state: New York
city: New Hyde Park
country: United States
facility: Chiesi Clinical Trial Site 84019
state: New York
city: Valhalla
country: United States
facility: Chiesi Clinical Trial Site 84009
state: New York
city: Greenville
country: United States
facility: Chiesi Clinical Trial Site 84027
state: North Carolina
city: Wilmington
country: United States
facility: Chiesi Clinical Trial Site 84010
state: North Carolina
city: Cincinnati
country: United States
facility: Chiesi Clinical Trial Site 84025
state: Ohio
city: Oklahoma City
country: United States
facility: Chiesi Clinical Trial Site 84017
state: Oklahoma
city: Hershey
country: United States
facility: Chiesi Clinical Trial Site 84020
state: Pennsylvania
city: Nashville
country: United States
facility: Chiesi Clinical Trial Site 84007
state: Tennessee
city: Lubbock
country: United States
facility: Chiesi Clinical Trial Site 84011
state: Texas
city: Plano
country: United States
facility: Chiesi Clinical Trial Site 84006
state: Texas
city: Temple
country: United States
facility: Chiesi Clinical Trial Site 84022
state: Texas
city: Charlottesville
country: United States
facility: Chiesi Clinical Trial Site 84015
state: Virginia
Study officials:
affiliation: LAC+USC Medical Center & Good Samaritan Hospital
name: Rangasamy Ramanathan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: