Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA

Respiratory Distress Syndrome Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02528318
• Other study ID #: 03-CL-1401
• Status: Terminated
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: August 11, 2017

Study information

• Verified date: July 2019
• Source: Windtree Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: August 11, 2017
• Est. primary completion date: May 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 26 Weeks to 28 Weeks

Eligibility

Inclusion Criteria:

1. Informed consent from a legally authorized representative.

2. Gestational age 26 to 28 completed weeks post menstrual age (PMA).

3. Successful implementation of controlled nCPAP within 90 minutes after birth.

4. Spontaneous breathing.

5. Chest radiograph consistent with RDS.

6. 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:

1. Heart rate that cannot be stabilized above 100 beats/minute within 5 minutes of birth.

2. 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.

3. A 5 minute Apgar score < 5.

4. Major congenital malformation(s) and cranial/facial abnormalities that preclude nCPAP, diagnosed antenatally or immediately after birth.

5. Other diseases or conditions potentially interfering with cardiopulmonary function (eg, hydrops fetalis or congenital infection such as TORCH).

6. Known or suspected chromosomal abnormality or syndrome.

7. Premature rupture of membranes (PROM) > 2 weeks.

8. Evidence of hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis.

9. Need for endotracheal intubation and mechanical ventilation.

10. Has been administered: another investigational agent or investigational medical device, any other surfactant agent, steroid treatment after birth.

Related Conditions & MeSH terms

• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Combination Product:
• Lucinactant for inhalation
Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product)

Device:
• nCPAP alone
nCPAP therapy

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Royal Alexandria Hospital	Edmonton	Alberta
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Chile	Hospital Dr Sotero Del Rio	Santiago
Chile	Hospital San Juan de Dios	Santiago
Poland	S.U. nr2im. Dr. Jana Biziela Oddzial Kliniczny N. W. Z. Intensywna Terapia Noworodka wraz z Wgjazdowy m Zespolem N	Bydgoszcz	Kujawsko-pomorksie
Poland	Instytut Centrum Zdrowja Matki Polki Klinika Neonatologii	Lodz	Lodzkie
Poland	Ginekologiczno-Polozniczy Szpital Klinicznym UM im. Karola Marcinkowskiego w Poznan i u Katedra Neonatologii	Poznan	Wielkopolskie
Poland	Szpital Kliniczny im. Ks, Anny Mazowieckiej Klinika Neonatologii	Warsaw	Mazowieckie
United States	Loma Linda University Medical Center	Loma Linda	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital - Morgan Stanley Children's Hospital	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Sharp Mary Birch Hospital for Women and Newborns	San Diego	California
United States	New Hanover Regional Medical Center	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Windtree Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	nCPAP Failure Without Treatment Interruptions	Number of subjects requiring mechanical ventilation or surfactant administration (nCPAP failure) but did not have a treatment interruption	Randomization to 72 Hours Post Randomization
Primary	Number of Participants With Peri-Dosing Adverse Events - Initial Dose	Number of Participants with adverse events that were experienced during the initial study treatment	Randomization to 24 Hours Post Randomization
Primary	Number of Participants With Air Leak	Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema)	7 days
Secondary	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)	Randomization to 72 Hours Post Randomization
Secondary	Bronchopulmonary Dysplasia	Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA)	Randomization to 36 weeks PMA
Secondary	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	Randomization to 72 Hours Post Randomization
Secondary	Death	Number of participants who died during the study	Randomization to 36 weeks PMA
Secondary	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.	Randomization to 72 hours post randomization
Secondary	Number of Participants With Complications of Prematurity	Number of participants with pre-specified common complications of prematurity.	Randomization to 36 weeks PMA