Back to resultsTrial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA
Primary Purpose
Respiratory Distress Syndrome
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lucinactant for inhalation
nCPAP alone
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Distress Syndrome
Eligibility Criteria
Inclusion Criteria:
- Informed consent from a legally authorized representative.
- Gestational age 26 to 28 completed weeks post menstrual age (PMA).
- Successful implementation of controlled nCPAP within 90 minutes after birth.
- Spontaneous breathing.
- Chest radiograph consistent with RDS.
- Within the first 20 hours after birth, have an nCPAP of 5 to 6 cm H2O to maintain oxygen saturation measured by pulse oximetry (SpO2) of 88% to 95% with a fraction of inspired oxygen (FiO2) of 0.25 to 0.50 that is clinically indicated for at least 30 minutes. Transient (<10 minutes) FiO2 excursions below 0.25 or above 0.50 did not reset the 30 minute requirement.
Exclusion Criteria:
- Heart rate that cannot be stabilized above 100 beats/minute within 5 minutes of birth.
- Recurrent episodes of apnea occurring after the initial newborn resuscitation period (ie, 10 minutes after birth) requiring intermittent positive pressure breaths using inflating pressures above the set CPAP pressure administered manually or mechanically through any patient interface.
- A 5 minute Apgar score < 5.
- Major congenital malformation(s) and cranial/facial abnormalities that preclude nCPAP, diagnosed antenatally or immediately after birth.
- Other diseases or conditions potentially interfering with cardiopulmonary function (eg, hydrops fetalis or congenital infection such as TORCH).
- Known or suspected chromosomal abnormality or syndrome.
- Premature rupture of membranes (PROM) > 2 weeks.
- Evidence of hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis.
- Need for endotracheal intubation and mechanical ventilation.
- Has been administered: another investigational agent or investigational medical device, any other surfactant agent, steroid treatment after birth.
Sites / Locations
- Loma Linda University Medical Center
- Sharp Mary Birch Hospital for Women and Newborns
- Christiana Care Health System
- University of Miami
- University of Louisville
- University of Nebraska Medical Center
- Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital - Morgan Stanley Children's Hospital
- New Hanover Regional Medical Center
- Providence St. Vincent Medical Center
- Women and Infants Hospital
- Foothills Medical Centre
- Royal Alexandria Hospital
- Sunnybrook Health Sciences Centre
- Montreal Children's Hospital
- Hospital Dr Sotero Del Rio
- Hospital San Juan de Dios
- S.U. nr2im. Dr. Jana Biziela Oddzial Kliniczny N. W. Z. Intensywna Terapia Noworodka wraz z Wgjazdowy m Zespolem N
- Instytut Centrum Zdrowja Matki Polki Klinika Neonatologii
- Szpital Kliniczny im. Ks, Anny Mazowieckiej Klinika Neonatologii
- Ginekologiczno-Polozniczy Szpital Klinicznym UM im. Karola Marcinkowskiego w Poznan i u Katedra Neonatologii
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Arm Label
50 mg/kg
75 mg/kg
100 mg/kg
150 mg/kg
nCPAP alone
Arm Description
Lucinactant for inhalation 50 mg total phospholipids (TPL)/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met.
Lucinactant for inhalation 75 mg TPL/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met.
Lucinactant for inhalation 100 mg TPL/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met.
Lucinactant for inhalation 150 mg TPL/kg with nCPAP 1 repeat dose will be allowed if repeat dosing criteria are met.
nCPAP therapy alone
Outcomes
Primary Outcome Measures
Number of Participants With Peri-Dosing Adverse Events - Initial Dose
Number of Participants with adverse events that were experienced during the initial study treatment
Number of Participants With Air Leak
Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema)
Secondary Outcome Measures
Number of Participants With Worsening of Respiratory Status Criteria
Number of participants with worsening in one of 12 respiratory status criteria through 72 hours post randomization (need for additional surfactant therapy, desaturation < 80%, heart rate < 100 bpm, sustained fraction of inspired oxygen (FiO2) > 0.50, arterial carbon dioxide (PCO2) > 65 mmHg, sustained apnea, persistent arterial pH < 7.2, intubation for any reason, nCPAP > 7 cmH2O, initiation of intermittent positive pressure ventilation, death, principal investigator determination of worsening status)
Bronchopulmonary Dysplasia
Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA)
Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure
Participants who required intubation for mechanical ventilation or surfactant administration were defined as having failed nCPAP
Death
Number of participants who died during the study
FiO2
Observed and change from baseline measurements for fraction of inspired oxygen (FiO2). Values represent the amount (fraction) of oxygen in the air the participant inspires; the values themselves do not have units. The normal amount of oxygen in air ("room air") is 21%, or 0.21.
Number of Participants With Complications of Prematurity
Number of participants with pre-specified common complications of prematurity.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02528318
Brief Title
Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA
Official Title
A Multicenter, Randomized, Open-label, Controlled Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision to terminate after 3 dosing groups
Study Start Date
August 2015 (Actual)
Primary Completion Date
May 31, 2017 (Actual)
Study Completion Date
August 11, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Windtree Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in up to four escalating doses to preterm neonates 26 to 28 weeks gestational age who are receiving nCPAP for RDS compared to neonates receiving nCPAP alone.
Detailed Description
This study was a multicenter, randomized, controlled, open-label, dose-escalation study, conducted to evaluate the safety and tolerability of lucinactant for inhalation in conjunction with nasal continuous positive airway pressure (nCPAP) in comparison with nCPAP alone. The study was to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in 4 escalating doses.
For this study, lucinactant for inhalation refers to the active investigational agent, lyophilized lucinactant, in combination with the prototype investigational delivery device. Reconstituted lyophilized lucinactant was aerosolized by the investigational device and introduced into the nCPAP circuit. Those randomized to the control arm continued to receive nCPAP alone. Dose assignments were unblinded, as the primary objective of this study was safety and tolerability.
Preterm neonates with respiratory distress syndrome (RDS) between 26 and 28 completed weeks PMA who were within the first 20 hours after birth and who had successful implementation of controlled nCPAP within 90 minutes of birth were considered to be potential subjects. Before study enrollment, legal guardians were provided a written informed consent form (ICF) for each potential subject.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Distress Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
50 mg/kg
Arm Type
Experimental
Arm Description
Lucinactant for inhalation 50 mg total phospholipids (TPL)/kg with nCPAP
1 repeat dose allowed if repeat dosing criteria are met.
Arm Title
75 mg/kg
Arm Type
Experimental
Arm Description
Lucinactant for inhalation 75 mg TPL/kg with nCPAP
1 repeat dose allowed if repeat dosing criteria are met.
Arm Title
100 mg/kg
Arm Type
Experimental
Arm Description
Lucinactant for inhalation 100 mg TPL/kg with nCPAP
1 repeat dose allowed if repeat dosing criteria are met.
Arm Title
150 mg/kg
Arm Type
Experimental
Arm Description
Lucinactant for inhalation 150 mg TPL/kg with nCPAP
1 repeat dose will be allowed if repeat dosing criteria are met.
Arm Title
nCPAP alone
Arm Type
Active Comparator
Arm Description
nCPAP therapy alone
Intervention Type
Combination Product
Intervention Name(s)
Lucinactant for inhalation
Other Intervention Name(s)
AEROSURF®
Intervention Description
Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product)
Intervention Type
Device
Intervention Name(s)
nCPAP alone
Other Intervention Name(s)
nasal continuous positive airway pressure
Intervention Description
nCPAP therapy
Primary Outcome Measure Information:
Title
Number of Participants With Peri-Dosing Adverse Events - Initial Dose
Description
Number of Participants with adverse events that were experienced during the initial study treatment
Time Frame
Randomization to 24 Hours Post Randomization
Title
Number of Participants With Air Leak
Description
Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema)
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Number of Participants With Worsening of Respiratory Status Criteria
Description
Number of participants with worsening in one of 12 respiratory status criteria through 72 hours post randomization (need for additional surfactant therapy, desaturation < 80%, heart rate < 100 bpm, sustained fraction of inspired oxygen (FiO2) > 0.50, arterial carbon dioxide (PCO2) > 65 mmHg, sustained apnea, persistent arterial pH < 7.2, intubation for any reason, nCPAP > 7 cmH2O, initiation of intermittent positive pressure ventilation, death, principal investigator determination of worsening status)
Time Frame
Randomization to 72 Hours Post Randomization
Title
Bronchopulmonary Dysplasia
Description
Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA)
Time Frame
Randomization to 36 weeks PMA
Title
Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure
Description
Participants who required intubation for mechanical ventilation or surfactant administration were defined as having failed nCPAP
Time Frame
Randomization to 72 Hours Post Randomization
Title
Death
Description
Number of participants who died during the study
Time Frame
Randomization to 36 weeks PMA
Title
FiO2
Description
Observed and change from baseline measurements for fraction of inspired oxygen (FiO2). Values represent the amount (fraction) of oxygen in the air the participant inspires; the values themselves do not have units. The normal amount of oxygen in air ("room air") is 21%, or 0.21.
Time Frame
Randomization to 72 hours post randomization
Title
Number of Participants With Complications of Prematurity
Description
Number of participants with pre-specified common complications of prematurity.
Time Frame
Randomization to 36 weeks PMA
Other Pre-specified Outcome Measures:
Title
nCPAP Failure Without Treatment Interruptions
Description
Number of subjects requiring mechanical ventilation or surfactant administration (nCPAP failure) but did not have a treatment interruption
Time Frame
Randomization to 72 Hours Post Randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
26 Weeks
Maximum Age & Unit of Time
28 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Informed consent from a legally authorized representative.
Gestational age 26 to 28 completed weeks post menstrual age (PMA).
Successful implementation of controlled nCPAP within 90 minutes after birth.
Spontaneous breathing.
Chest radiograph consistent with RDS.
Within the first 20 hours after birth, have an nCPAP of 5 to 6 cm H2O to maintain oxygen saturation measured by pulse oximetry (SpO2) of 88% to 95% with a fraction of inspired oxygen (FiO2) of 0.25 to 0.50 that is clinically indicated for at least 30 minutes. Transient (<10 minutes) FiO2 excursions below 0.25 or above 0.50 did not reset the 30 minute requirement.
Exclusion Criteria:
Heart rate that cannot be stabilized above 100 beats/minute within 5 minutes of birth.
Recurrent episodes of apnea occurring after the initial newborn resuscitation period (ie, 10 minutes after birth) requiring intermittent positive pressure breaths using inflating pressures above the set CPAP pressure administered manually or mechanically through any patient interface.
A 5 minute Apgar score < 5.
Major congenital malformation(s) and cranial/facial abnormalities that preclude nCPAP, diagnosed antenatally or immediately after birth.
Other diseases or conditions potentially interfering with cardiopulmonary function (eg, hydrops fetalis or congenital infection such as TORCH).
Known or suspected chromosomal abnormality or syndrome.
Premature rupture of membranes (PROM) > 2 weeks.
Evidence of hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis.
Need for endotracheal intubation and mechanical ventilation.
Has been administered: another investigational agent or investigational medical device, any other surfactant agent, steroid treatment after birth.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steve Simonson, MD
Organizational Affiliation
Windtree Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Sharp Mary Birch Hospital for Women and Newborns
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Christiana Care Health System
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital - Morgan Stanley Children's Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
New Hanover Regional Medical Center
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Providence St. Vincent Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Women and Infants Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Facility Name
Royal Alexandria Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5H 3V9
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Hospital Dr Sotero Del Rio
City
Santiago
ZIP/Postal Code
8207257
Country
Chile
Facility Name
Hospital San Juan de Dios
City
Santiago
ZIP/Postal Code
8350488
Country
Chile
Facility Name
S.U. nr2im. Dr. Jana Biziela Oddzial Kliniczny N. W. Z. Intensywna Terapia Noworodka wraz z Wgjazdowy m Zespolem N
City
Bydgoszcz
State/Province
Kujawsko-pomorksie
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Instytut Centrum Zdrowja Matki Polki Klinika Neonatologii
City
Lodz
State/Province
Lodzkie
ZIP/Postal Code
93-338
Country
Poland
Facility Name
Szpital Kliniczny im. Ks, Anny Mazowieckiej Klinika Neonatologii
City
Warsaw
State/Province
Mazowieckie
ZIP/Postal Code
00-315
Country
Poland
Facility Name
Ginekologiczno-Polozniczy Szpital Klinicznym UM im. Karola Marcinkowskiego w Poznan i u Katedra Neonatologii
City
Poznan
State/Province
Wielkopolskie
ZIP/Postal Code
60-535
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA
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