Trial Outcomes & Findings for Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia (NCT NCT01022580)

NCT ID: NCT01022580

Last Updated: 2021-05-13

Results Overview

BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 511 participants
• Primary outcome timeframe: 36 weeks post menstrual age +/- 1 week
• Results posted on: 2021-05-13

Participant Flow

Participant milestones

Measure	Infasurf Surfactant (ONY, Inc.) Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8.	Sham Infants already receiving inhaled nitric oxide will not receive additional doses of late surfactant (Infasurf).
Overall Study STARTED	252	259
Overall Study COMPLETED	234	237
Overall Study NOT COMPLETED	18	22

Reasons for withdrawal

Measure	Infasurf Surfactant (ONY, Inc.) Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8.	Sham Infants already receiving inhaled nitric oxide will not receive additional doses of late surfactant (Infasurf).
Overall Study Death	18	22

Baseline Characteristics

Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia

Baseline characteristics by cohort

Measure	Infasurf Surfactant (ONY, Inc.) n=252 Participants Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8.	Sham n=259 Participants Infants already receiving inhaled nitric oxide will not receive additional doses of late surfactant (Infasurf).	Total n=511 Participants Total of all reporting groups
Age, Continuous Gestational Age Weeks	25.2 weeks STANDARD_DEVIATION 1.2 • n=5 Participants	25.2 weeks STANDARD_DEVIATION 1.2 • n=7 Participants	25.2 weeks STANDARD_DEVIATION 1.2 • n=5 Participants
Sex: Female, Male Female	109 Participants n=5 Participants	121 Participants n=7 Participants	230 Participants n=5 Participants
Sex: Female, Male Male	143 Participants n=5 Participants	138 Participants n=7 Participants	281 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	33 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	227 Participants n=5 Participants	225 Participants n=7 Participants	452 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	99 Participants n=5 Participants	91 Participants n=7 Participants	190 Participants n=5 Participants
Race (NIH/OMB) White	134 Participants n=5 Participants	157 Participants n=7 Participants	291 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Respiratory Severity Score (RSS) - MAP x FiO2	3.7 score on a scale STANDARD_DEVIATION 2.3 • n=5 Participants	3.8 score on a scale STANDARD_DEVIATION 2.2 • n=7 Participants	3.75 score on a scale STANDARD_DEVIATION 3.25 • n=5 Participants
Birthweight	700.1 grams STANDARD_DEVIATION 173.2 • n=5 Participants	702.3 grams STANDARD_DEVIATION 156.0 • n=7 Participants	701 grams STANDARD_DEVIATION 160 • n=5 Participants

PRIMARY outcome

Timeframe: 36 weeks post menstrual age +/- 1 week

BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction.

Outcome measures

Measure	Infasurf Surfactant (ONY, Inc.) n=252 Participants Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, and repeated Q24-72 hours as long as infant remains ventilated. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, and repeated Q24-72 hours as long as infant remains ventilated.	Sham n=259 Participants Infants already receiving inhaled nitric oxide will receive scheduled sham (nothing done) doses of late surfactant (nothing done). Sham (nothing done) doses will be given to infants on study days 0,and repeated Q24-72 hours as long as infant remains ventilated.
Survival Without BPD at 36 Weeks Post Menstrual Age.	79 Participants	82 Participants

SECONDARY outcome

Timeframe: 40 weeks PMA +/- 1 week

Population: Infants who were No BPD at 36 wk were imputed to be No BPD at 40 wk. Infants discharged on oxygen without a challenge test were assigned Yes BPD.

BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction.

Outcome measures

Measure	Infasurf Surfactant (ONY, Inc.) n=252 Participants Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, and repeated Q24-72 hours as long as infant remains ventilated. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, and repeated Q24-72 hours as long as infant remains ventilated.	Sham n=259 Participants Infants already receiving inhaled nitric oxide will receive scheduled sham (nothing done) doses of late surfactant (nothing done). Sham (nothing done) doses will be given to infants on study days 0,and repeated Q24-72 hours as long as infant remains ventilated.
Survival Without BPD at 40 Weeks	148 Participants	140 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Infants who survived to discharge and had data from questionaires available

Evaluation of respiratory outcome through the first 12 months after birth. questionnaires were administered by phone at 3,6,9 and 12 months to determine respiratory resource use (medications, home support, and hospitalization) No Pulmonary Morbidity (NoPM) was reported for infants who had no resource use in any quarter and Persistent PM was reported for infants having resource use in 3 or 4 quarters.

Outcome measures

Measure	Infasurf Surfactant (ONY, Inc.) n=208 Participants Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, and repeated Q24-72 hours as long as infant remains ventilated. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, and repeated Q24-72 hours as long as infant remains ventilated.	Sham n=240 Participants Infants already receiving inhaled nitric oxide will receive scheduled sham (nothing done) doses of late surfactant (nothing done). Sham (nothing done) doses will be given to infants on study days 0,and repeated Q24-72 hours as long as infant remains ventilated.
Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age Home respiratory support	80 Participants	118 Participants
Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age No PM	54 Participants	47 Participants
Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age Persistent PM	74 Participants	75 Participants

SECONDARY outcome

Timeframe: 2 years

Evaluation of pulmonary outcome at 24 months of age. Evaluation of persistent wheezing based on reported wheezing during both first and second year of life.

Outcome measures

Measure	Infasurf Surfactant (ONY, Inc.) n=203 Participants Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, and repeated Q24-72 hours as long as infant remains ventilated. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, and repeated Q24-72 hours as long as infant remains ventilated.	Sham n=217 Participants Infants already receiving inhaled nitric oxide will receive scheduled sham (nothing done) doses of late surfactant (nothing done). Sham (nothing done) doses will be given to infants on study days 0,and repeated Q24-72 hours as long as infant remains ventilated.
Pulmonary Outcomes Through 2 Years of Age	91 Participants	98 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Neurodevelopmental testing occurred with only 322 participants.

At 24 months corrected age, children underwent neuropsychological testing with the Bayley Scales of Infant Development-Third Edition (Bayley-3), and composite cognitive, language, and motor scores were collected as well as subscale scores in receptive and expressive speech and fine and gross motor. Infants with greater than one impairment as identified by testing were classified as having neurodevelopmental impairment.

Outcome measures

Measure	Infasurf Surfactant (ONY, Inc.) n=154 Participants Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, and repeated Q24-72 hours as long as infant remains ventilated. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, and repeated Q24-72 hours as long as infant remains ventilated.	Sham n=168 Participants Infants already receiving inhaled nitric oxide will receive scheduled sham (nothing done) doses of late surfactant (nothing done). Sham (nothing done) doses will be given to infants on study days 0,and repeated Q24-72 hours as long as infant remains ventilated.
Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years.	28 percentage of participants	32 percentage of participants

Adverse Events

Infasurf Surfactant (ONY, Inc.)

Serious events: 29 serious events

Other events: 141 other events

Deaths: 29 deaths

Sham (No Treatment)

Serious events: 24 serious events

Other events: 153 other events

Deaths: 24 deaths

Serious adverse events

Measure	Infasurf Surfactant (ONY, Inc.) n=252 participants at risk Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.	Sham (No Treatment) n=259 participants at risk Infants already receiving inhaled nitric oxide will receive "Sham (no treatment)" doses on study days 0,2,4,6, and 8. Sham (No Treatment): Late doses of Sham (No treatment) will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.
Investigations Death	11.5% 29/252 • Number of events 29	9.3% 24/259 • Number of events 24

Other adverse events

Measure	Infasurf Surfactant (ONY, Inc.) n=252 participants at risk Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8. Infasurf surfactant (ONY, Inc.): Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.	Sham (No Treatment) n=259 participants at risk Infants already receiving inhaled nitric oxide will receive "Sham (no treatment)" doses on study days 0,2,4,6, and 8. Sham (No Treatment): Late doses of Sham (No treatment) will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.
General disorders IVH New or Worsened	13.1% 33/252 • Number of events 33	13.5% 35/259 • Number of events 35
Cardiac disorders PDA Requiring Treatment	35.3% 89/252 • Number of events 89	36.7% 95/259 • Number of events 95
Gastrointestinal disorders NEC	10.7% 27/252 • Number of events 27	9.3% 24/259 • Number of events 24
Infections and infestations Sepsis	56.0% 141/252 • Number of events 141	59.1% 153/259 • Number of events 153
Eye disorders ROP Class 4-5 or surgery	13.5% 34/252 • Number of events 34	11.2% 29/259 • Number of events 29

Additional Information

Roberta A Ballard, MD

University of California, San Francisco

Phone: 415-476-4193

Email: roberta.ballard@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place