A Study in Preterm Neonates With Respiratory Distress Syndrome (RDS) Comparing CUROSURF® Administration Through Less Invasive Surfactant Administration (LISA) and Conventional Administration
- Conditions
- Respiratory Distress Syndrome (RDS)
- Interventions
- Combination Product: LISA combination product (Curosurf+catheter CHF6440)
- Registration Number
- NCT02772081
- Lead Sponsor
- Chiesi Farmaceutici S.p.A.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 33
- Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth
- Preterm neonates of either sex aged ≥30 minutes and <24 hours, spontaneously breathing and stabilized on non-invasive ventilation (NIV).
- 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.
- Clinical course consistent with RDS.
- Fraction of inspired oxygen (FiO2) ≥0.30 to maintain preductal oxygen saturation (SpO2) between 88-95%.
- Need for immediate endotracheal intubation for cardiopulmonary resuscitation or insufficient respiratory drive
- Use of nasal high frequency oscillatory ventilation (nHFOV) prior to study entry
- Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
- Known genetic or chromosomal disorders, major congenital anomalies (congenital heart diseases, myelomeningocele etc)
- Mothers with prolonged rupture of the membranes (> 21 days duration)
- Presence of air leaks if identified and known prior to study entry
- Evidence of severe birth asphyxia (e.g. continued need for resuscitation at 10 minutes after birth, altered neurological state, or neonatal encephalopathy)
- Neonatal seizures prior to study entry
- Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Curosurf LISA LISA combination product (Curosurf+catheter CHF6440) Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf Endotracheal Tube Curosurf through conventional administration (endotracheal tube) Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed.
- Primary Outcome Measures
Name Time Method Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion At first surfactant administration, up to Day 1 or at second administration, up to 2 days. Number of attempts required to achieve first successful insertion is presented by treatment group.
Safety: Study Treatment Administration: Duration of Surfactant Administration At first surfactant administration, up to Day 1 or at second administration, up to 2 days. Duration of surfactant administration is presented by treatment group.
Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment First 72 hours of life. Extent of exposure to study treatment is summarized by treatment group. Number of participants who received 1, 2, or 3 doses of treatment.
All neonates received the first administration of Curosurf® 200 mg/kg. In case of lack of efficacy or clinical deterioration, a second dose of Curosurf® 100 mg/kg was administered using the same technique as the first dose. Neonates could receive a third Curosurf® 100 mg/kg dose if needed, administered using a standard technique. Results are presented as the number of neonates who received 1, 2, or 3 doses of Curosurf®, administered.Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube At first surfactant administration, up to Day 1. Number of participants for whom the first attempt failed to insert the catheter/endotracheal tube and the percentage of neonates with first failed attempt, is presented by treatment group.
Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization At first surfactant administration, up to Day 1 or at second administration, up to 2 days. Number of manoeuvres (attempts) discontinued, due to neonate's severe destabilization is presented by treatment group.
Safety: Study Treatment Administration: Duration of the Whole Procedure At first surfactant administration, up to Day 1 or at second administration, up to 2 days. Duration of the whole procedure (starting from the insertion of laryngoscope up to the removal of the catheter/ETT), is presented by treatment group.
Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion) At first surfactant administration, up to Day 1 or at second administration, up to 2 days. Number of device misallocation for LISA administration group (esophageal insertion).
Data was not collected from participants in the "Curosurf Endotracheal Tube" -- the control arm of the study, because it is not applicable.
- Secondary Outcome Measures
Name Time Method Efficacy: Blood Gas Analysis Parameters -- pH First 72 hours of life (1h, 6h, 24h, 48h, 72h) The blood gas analysis for blood pH at all timepoints and the changes from pre-procedure to each timepoint are presented.
Results for pH values are based on a scale of 0 to 14. A pH value of 7 is neutral, pH less than 7 is acidic, and pH greater than 7 is basic.Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks Post-Menstrual Age (PMA). The duration of oxygen alone supplementation and any non-invasive ventilation (NIV) during the study are presented by treatment group.
PMA=Post-Menstrual Age PNA=Post-Natal AgeEfficacy: Neonates Needing Additional Surfactant Doses First 72 hours of life. A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group.
Efficacy: Preductal Oxygen Saturation (SpO2) 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. The mean SpO2 values at timepoints up to and including 120 hours post-treatment are summarized by treatment group.
Oxygen saturation (SpO2) is a measurement of how much oxygen the blood is carrying as a percentage of the maximum it could carry.Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study Up to 28 days PNA, Up to 36 weeks PMA The duration of invasive ventilation (MV) in the first 28 days PNA, and within 36 weeks PMA, are presented by treatment group.
Participants who actually received invasive ventilation are reported in the table below.Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks PMA The percentage of neonates needing invasive mechanical ventilation (MV) in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-Menstrual Age (PMA), and respective statistical analyses, are presented by treatment group.
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) First 72 hours of life (1h, 6h, 24h, 48h, 72h) The blood gas analysis partial pressure of oxygen (pO2) at all timepoints and the changes from pre-procedure to each timepoint are presented.
Efficacy: Blood Analysis Parameter -- Lactate First 72 hours of life (1h, 6h, 24h, 48h, 72h) The blood concentration of lactate at all timepoints and the changes from pre-procedure to each timepoint are presented.
Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant First 72 hours of life. A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group i.e. 2 or 3 doses of surfactant .
Efficacy: Fraction of Inspired Oxygen (FiO2) 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. The FiO2 values at timepoints up to and including 120 hours post-treatment and the changes from pre-procedure to each of those timepoints are presented by treatment group.
The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture.Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period First 72 hours of life, up to 28 days post-natal age (PNA), Up to 36 weeks Post-menstrual age (PMA) The percentage of neonates needing any intubation procedure, outside the initial surfactant administration period (i.e., excluding endotracheal intubation\[s\] that were required for surfactant administration in the Conventional administration arm), in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-menstrual age (PMA), and respective statistical analyses, are presented.
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) First 72 hours of life (1h, 6h, 24h, 48h, 72h) The blood concentration of bicarbonate (HCO3\^-) at all timepoints and the changes from pre-procedure to each timepoint are presented.
Efficacy: Blood Analysis Parameter -- Base Excess First 72 hours of life (1h, 6h, 24h, 48h, 72h) The blood base excess at all timepoints and the changes from pre-procedure to each timepoint are presented.
Base excess is defined as the amount of acid that must be added to each litre of fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg (5.3 kPa). The value is reported as a concentration in units of milliequivalent per liter (mEq/L), with positive numbers indicating an excess of base and negative a deficit.Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 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. The mean SpO2/FiO2 ratio values at timepoints up to and including 120 hours post-treatment, and respective statistical analyses, are summarized by treatment group.
Efficacy: Duration of Invasive Mechanical Ventilation During the Study First 72 hours of life The duration of invasive ventilation (MV) in the first 72 hours of life and respective statistical analyses, are presented by treatment group.
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) First 72 hours of life (1h, 6h, 24h, 48h, 72h) The blood gas analysis partial pressure of carbon dioxide (pCO2) at all timepoints and the changes from pre-procedure to each timepoint are presented.
Trial Locations
- Locations (26)
Chiesi Clinical Trial Site 84002
🇺🇸Los Angeles, California, United States
Chiesi Clinical Trial Site 84012
🇺🇸Camden, New Jersey, United States
Chiesi Clinical Trial Site 84024
🇺🇸Manhasset, New York, United States
Chiesi Clinical Trial Site 84013
🇺🇸Denver, Colorado, United States
Chiesi Clinical Trial Site 84025
🇺🇸Cincinnati, Ohio, United States
Chiesi Clinical Trial Site 84007
🇺🇸Nashville, Tennessee, United States
Chiesi Clinical Trial Site 84029
🇺🇸Little Rock, Arkansas, United States
Chiesi Clinical Trial Site 84001
🇺🇸Los Angeles, California, United States
Chiesi Clinical Trial Site 84026
🇺🇸New Britain, Connecticut, United States
Chiesi Clinical Trial Site 84023
🇺🇸Lexington, Kentucky, United States
Chiesi Clinical Trial Site 84021
🇺🇸Peoria, Illinois, United States
Chiesi Clinical Trial Site 84004
🇺🇸Saint Louis, Missouri, United States
Chiesi Clinical Trial Site 84028
🇺🇸Springfield, Massachusetts, United States
Chiesi Clinical Trial Site 84005
🇺🇸Worcester, Massachusetts, United States
Chiesi Clinical Trial Site 84019
🇺🇸New Hyde Park, New York, United States
Chiesi Clinical Trial Site 84017
🇺🇸Oklahoma City, Oklahoma, United States
Chiesi Clinical Trial Site 84010
🇺🇸Wilmington, North Carolina, United States
Chiesi Clinical Trial Site 84006
🇺🇸Plano, Texas, United States
Chiesi Clinical Trial Site 84022
🇺🇸Temple, Texas, United States
Chiesi Clinical Trial Site 84015
🇺🇸Charlottesville, Virginia, United States
Chiesi Clinical Trial Site 84011
🇺🇸Lubbock, Texas, United States
Chiesi Clinical Trial Site 84003
🇺🇸Evanston, Illinois, United States
Chiesi Clinical Trial Site 84020
🇺🇸Hershey, Pennsylvania, United States
Chiesi Clinical Trial Site 84008
🇺🇸Lansing, Michigan, United States
Chiesi Clinical Trial Site 84027
🇺🇸Greenville, North Carolina, United States
Chiesi Clinical Trial Site 84009
🇺🇸Valhalla, New York, United States