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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04545866
Other study ID # NICHD-NRN-0064
Secondary ID UG1HD034216UG1HD
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date April 1, 2021
Est. completion date September 30, 2027

Study information

Verified date July 2023
Source NICHD Neonatal Research Network
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a Phase 3, randomized, masked, active-controlled, multicenter trial designed to determine whether early intratracheal administration of a combination of budesonide with surfactant, as compared to surfactant alone, will reduce the incidence of physiologic bronchopulmonary dysplasia (BPD) or death by 36 weeks' post-menstrual age in extremely preterm infants.


Description:

From a study of 9575 extremely preterm (22-28 weeks gestational age and 401-1500g birth weight) infants born between 2003 and 2007 and enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN), it is anticipated that 93% of extremely preterm infants will develop respiratory distress syndrome, 68% will develop bronchopulmonary dysplasia (BPD), 16% will develop severe intraventricular hemorrhage, and 36% will develop late-onset sepsis (PMID: 20732945). Furthermore, in 2014 20% of the infants enrolled in the NRN Generic Database (GDB) died (8% by less than 12 hours, 12% between 12 hours and 120 days, and 1% after 120 days) and 47% of infants who survived to 36 weeks' post-menstrual age (PMA) developed physiologic BPD (NRN GDB data). BPD is therefore one of the most common morbidities in extremely preterm infants. Death is a competing outcome for BPD, as infants who die before ascertainment of BPD at 36 weeks' PMA cannot be diagnosed with BPD even though they may have been at the highest risk. As children get older, BPD has been shown to be associated with worse cognitive outcomes in school age and with abnormal pulmonary function in adolescence and adulthood (PMID: 14595077; 15499947; 2247118). Recent randomized trials have indicated a lower incidence of BPD/death with the use of a combination of budesonide with surfactant (budesonide + surfactant) compared to surfactant alone when administered soon after birth. Therefore, after obtaining informed consent and confirming eligibility for the trial, infants are randomized in a 1:1 allocation ratio to either the budesonide + surfactant arm or the surfactant alone arm within 48 hours of birth.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 1160
Est. completion date September 30, 2027
Est. primary completion date September 30, 2025
Accepts healthy volunteers No
Gender All
Age group N/A to 48 Hours
Eligibility Inclusion Criteria: - Liveborn infants 22 0/7 - 28 6/7 weeks gestation or 401 - 1000 grams (inclusive) birth weight - Clinical decision to give surfactant - Less than or equal to 48 hours postnatal age Exclusion Criteria: - Terminal illness (heart rate < 100 beats per minute, unresponsiveness to resuscitation) or unlikely to survive as judged by the clinician - Decision to redirect or limit support - Use of surfactant before enrollment (first dose of surfactant must be study drug) - Infant received systemic steroids prior to enrollment - Use of indomethacin, either received by the mother within 24 hours prior to delivery,received by the infant prior to enrollment, or intent to administer to the infant for IVH prophylaxis or PDA management from enrollment up to 7 days of final dose of study drug - Serious chromosomal abnormalities or major malformations - Known congenital infections including, but not limited to, confirmed sepsis, congenital CMV, etc. - Infants with a permanent neuromuscular condition that affects respiration - Enrollment in a conflicting clinical trial

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
budesonide (Pulmicort nebulizing suspension).
The first dose of budesonide is 0.25 mg/kg in a volume of 1 ml/kg, for a total volume of 2.5 ml/kg of Curosurf + 1 ml/kg of budesonide. If the infant is to receive a second dose of study drug within 50 hours of birth, the dosage of Curosurf is 1.25 ml/kg for the second dose and 1 ml/kg of budesonide.
surfactant (poractant alfa;Curosurf)
The first dose of surfactant (poractant alfa; Curosurf) is 2.5 ml/kg. If the infant is to receive a second dose of study drug within 50 hours of birth, the dosage of Curosurf is 1.25 ml/kg for the second dose.

Locations

Country Name City State
United States University of New Mexico Albuquerque New Mexico
United States Emory University Atlanta Georgia
United States University of Alabama Birmingham Alabama
United States Northwestern Lurie Children's Hospital of Chicago Chicago Illinois
United States Cincinnati Children's Medical Center Cincinnati Ohio
United States Case Western Reserve University, Rainbow Babies and Children's Hospital Cleveland Ohio
United States Research Institute at Nationwide Children's Hospital Columbus Ohio
United States University of Texas Southwestern Medical Center at Dallas Dallas Texas
United States Duke University Durham North Carolina
United States RTI International Durham North Carolina
United States University of Texas Health Science Center at Houston Houston Texas
United States University of Iowa Iowa City Iowa
United States University of Mississippi Medical Center - Children's of Mississippi Jackson Mississippi
United States Stanford University Palo Alto California
United States University of Pennsylvania Philadelphia Pennsylvania
United States Brown University - Women and Infants Hospital of Rhode Island Providence Rhode Island
United States University of Rochester Rochester New York
United States University of Utah Salt Lake City Utah
United States Sharp Mary Birch Hospital for Women & Newborns San Diego California

Sponsors (2)

Lead Sponsor Collaborator
NICHD Neonatal Research Network Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with Physiologic BPD or death Physiologic BPD or death by 36 weeks' PMA. Physiologic BPD is determined using existing NRN GDB criteria at 36 weeks' PMA. Randomization to 36 weeks' post-menstrual age
Secondary Number of Participants with Death by 36 weeks' post-menstrual age Death by 36 weeks' PMA Randomization to 36 weeks' post-menstrual age
Secondary Number of Participants with Physiologic BPD Physiologic BPD as determined by existing NRN GDB criteria at 36 weeks' PMA. 36 weeks' post-menstrual age
Secondary Grade of BPD Severity BPD severity is defined as in Jensen et al. (2019; PMID: 30995069) at 36 weeks' PMA according to treatment with the following respiratory support:
No BPD: room air;
Grade 1: nasal cannula at flow rates = 2 L/min;
Grade 2: nasal cannula at flow rates > 2 L/min or noninvasive positive airway pressure;
Grade 3: invasive mechanical ventilation.
36 weeks' post-menstrual age
Secondary Number of Participants with Grade 3 BPD Grade 3 BPD at 36 weeks' PMA according to the Jensen et al. (2019 PMID: 30995069) definition. 36 weeks' post-menstrual age
Secondary Number of Participants with Use of Additional Postnatal Steroids Use of postnatal steroids for treatment of evolving chronic lung disease (separate from study drug) from 7 days after the final dose of study drug through 36 weeks' PMA. 7 days post final dose of study drug through 36 weeks' post-menstrual age
Secondary Number of Participants with Severe Neurodevelopmental Impairment (NDI) Severe NDI is assessed at the 2-year follow-up (22-26 months corrected age). In light of the upcoming transition to BSID IV, severe NDI assessment will be based on the agreed upon definition at the time of the first participant's follow-up assessment. An example of such a definition could be presence of any of the following:
Cognitive composite score on the BSID IV < 70,
GMFCS level 3-5,
Severe hearing impairment (no functional hearing despite amplification), or
Bilateral severe visual impairment (bilateral blindness despite correction).
22-26 months corrected age
Secondary Number of Participants with Death by 2 years Death by 2-year follow-up (22-26 months corrected age) Randomization to 22-26 months corrected age
Secondary Number of Participants with Severe NDI or death Severe NDI or death as assessed at 2-year follow-up (22-26 months corrected age) Randomization to 22-26 months corrected age
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