Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction)Phase 3TOLSURFPilotNCT00569530

Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide

A Phase 3 study testing Infasurf (ONY Inc.) in people with Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction) and Bronchopulmonary Dysplasia, run by Roberta Ballard at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine if the combination of late doses of Infasurf with inhaled nitric oxide will interact to improve the surfactant function and thus the respiratory status and outcome of treated infants. Read more about this study

Who is it for?: Ages 7 to 14 days
Conditions the study is for: Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction), Bronchopulmonary Dysplasia
What is being tested?: Infasurf (ONY Inc.)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 85 participants
Where: 9 sitesUnited States
Study dates: Jan 2008to Dec 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 7 to 14 days
All sexes
No healthy volunteers
Child

Who may be able to join

Less than or equal to 1000 gm. birth weight
Less than or equal to 30 weeks gestational age
Day 7-14 of life
Intubated and mechanically ventilated at any time days 7-14 of life

Who cannot join

Serious congenital malformations
Life expectancy less than 7 days from enrollment
Previous treatment with iNO
Active pulmonary hemorrhage at time of enrollment
Active air leak syndrome at time of enrollment
Bilateral grade IV intracranial hemorrhage prior to enrollment
Less than 48 hours from last clinical dose of early surfactant.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

Alta Bates Summit Medical Center
Berkeley, California, 94705
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Children's Memorial Hospital
Chicago, Illinois, 60614
Texas Children's Hospital
Houston, Texas, 77030
Children's Mercy Hospital
Kansas City, Missouri, 64108
Children's Hospital Oakland
Oakland, California, 94609
University of California, San Francisco
San Francisco, California, 94143
Stony Brook University Medical Center
Stony Brook, New York, 11794

Other trials in United States

About this study

Read the detailed description

Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. The investigators conducted a multi-center, randomized, blinded pilot study to assess the safety and efficacy of late administration of surfactant (Calfactant - high in protein B) in combination with prolonged inhaled nitric oxide in preterm infants < 1000 grams birthweight (BW). Calfactant is one of several types of exogenous surfactant. Calfactant has the highest % of surfactant protein B of the different types.

Conditions: Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction), Bronchopulmonary Dysplasia
Being tested: Infasurf (ONY Inc.), Sham
Keywords: nitric oxide, surfactant, bronchopulmonary dysplasia, prematurity, neonates, iNO, Infasurf, lung function, ventilated infants
Medical subject headings: Respiratory Distress Syndrome, Surfactant Dysfunction, Bronchopulmonary Dysplasia, Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Infasurf (ONY Inc.)Drug
Also called Infasurf
Infasurf 3ml/kg will be given to infants on study days 0, 3, 7, 10, and 14, if remains intubated.
ShamDrug
Also called Air
Sham instillation (no treatment) will be given to study infants on days 0, 3, 7, 10, and 14, if remains intubated.

Study groups in NCT00569530
Study group	Role	What they receive
Treatment Surfactant (Infasurf) ONY, NY	Active comparator	Patients receive inhaled nitric oxide and scheduled doses of Infasurf on study days 0, 3, 7, 10, and 14, if infant remains ventilated. Receives: Drug: Infasurf (ONY Inc.)
Sham (no treatment)	Placebo comparator	Infants receiving inhaled nitric oxide will receive Sham (no treatment) on study days 0, 3, 7, 10, and 14, if infant remains ventilated. Receives: Drug: Sham

What is being measured

The primary outcome is the main question the study is designed to answer.

SP-B Content
SP-B Content is the surfactant protein B found in terms of percentage of phospholipid measured one day after surfactant or sham dose.
Measured: One day after dose

Secondary outcomes (1)

Alive Without BPD at 36 Weeks Post Menstrual Age
Alive without need for oxygen at 36 weeks post menstrual age.
Measured: 36 Weeks Post Menstrual Age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Dec 2012

First posted7 Dec 2007 (estimated)
Study startJan 2008
Primary completionDec 2012
Study completionDec 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 85 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00569530
Sponsor's protocol ID: H10842-31630-01
Other IDs: IND79367
Acronym: TOLSURFPilot
Status last verified: Apr 2021
First submitted: 5 Dec 2007
Last updated: 11 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE; NO CLD Study Group. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006 Jul 27;355(4):343-53. doi: 10.1056/NEJMoa061088.
PubMed 16870913
Ballard PL, Merrill JD, Truog WE, Godinez RI, Godinez MH, McDevitt TM, Ning Y, Golombek SG, Parton LA, Luan X, Cnaan A, Ballard RA. Surfactant function and composition in premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Aug;120(2):346-53. doi: 10.1542/peds.2007-0095.
PubMed 17671061
Truog WE, Ballard PL, Norberg M, Golombek S, Savani RC, Merrill JD, Parton LA, Cnaan A, Luan X, Ballard RA; Nitric Oxide (to Prevent) Chronic Lung Disease Study Investigators. Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Apr;119(4):670-8. doi: 10.1542/peds.2006-2683.
PubMed 17403837
Keller RL, Merrill JD, Black DM, Steinhorn RH, Eichenwald EC, Durand DJ, Ryan RM, Truog WE, Courtney SE, Ballard PL, Ballard RA. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res. 2012 Dec;72(6):613-9. doi: 10.1038/pr.2012.136. Epub 2012 Oct 4.
PubMed 23037875

Study at a glance

From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide
ClinicalTrials.gov ID: NCT00569530
Acronym / sponsor ID: TOLSURFPilot / H10842-31630-01
Conditions: Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction), Bronchopulmonary Dysplasia
Keywords: nitric oxide, surfactant, bronchopulmonary dysplasia, prematurity, neonates, iNO, Infasurf, lung function
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 85 participants (actual)
Lead sponsor: Roberta BallardUniversity, hospital or other
Collaborators: Mallinckrodt, ONY
Study start: Jan 2008
Primary completion: Dec 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 7 Dec 2007 (estimated)
Results: Posted 28 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Treatment Surfactant (Infasurf) ONY, NY	Active comparator	Drug: Infasurf (ONY Inc.)Patients receive inhaled nitric oxide and scheduled doses of Infasurf on study days 0, 3, 7, 10, and 14, if infant remains ventilated.
Sham (no treatment)	Placebo comparator	Drug: ShamInfants receiving inhaled nitric oxide will receive Sham (no treatment) on study days 0, 3, 7, 10, and 14, if infant remains ventilated.

Who may qualify

Ages: 7 to 14 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (4 listed)

Less than or equal to 1000 gm. birth weight
Less than or equal to 30 weeks gestational age
Day 7-14 of life
Intubated and mechanically ventilated at any time days 7-14 of life

Key exclusion criteria (7 listed)

Serious congenital malformations
Life expectancy less than 7 days from enrollment
Previous treatment with iNO
Active pulmonary hemorrhage at time of enrollment
Active air leak syndrome at time of enrollment

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Infasurf (ONY Inc.)Also: InfasurfInfasurf 3ml/kg will be given to infants on study days 0, 3, 7, 10, and 14, if remains intubated.	Drug	Treatment Surfactant (Infasurf) ONY, NY
ShamAlso: AirSham instillation (no treatment) will be given to study infants on days 0, 3, 7, 10, and 14, if remains intubated.	Drug	Sham (no treatment)

Primary outcome

SP-B Content
Time frame: One day after dose
SP-B Content is the surfactant protein B found in terms of percentage of phospholipid measured one day after surfactant or sham dose.

1 secondary outcome

Alive Without BPD at 36 Weeks Post Menstrual Age
Time frame: 36 Weeks Post Menstrual Age

Results and safety

Results posted to the registry on 28 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Surfactant (Infasurf) ONY, NY	43	43
Sham (no Treatment)	42	42

Primary outcome: SP-B Content

Time frame: One day after dose. Mean (Full Range). Unit: Total surfactant protein (% of PL)

Measure	Treatment Surfactant (Infasurf) ONY, NY n = 24	Sham (no Treatment) n = 18
Value	19.9 (3.7 to 71.0)	13.3 (4.3 to 47.8)

Population analysed: 24 of 43 in the Treatment Group and 18 of 42 in the Sham group had samples analyzed. SpB content recorded as a percentage of Total Phospholipids.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Surfactant (Infasurf) ONY, NY	0 of 43 (0%)	0 of 43 (0%)	Not reported
Sham (no Treatment)	0 of 42 (0%)	0 of 42 (0%)	Not reported

Limitations and caveats (from the sponsor): More frequent dosing, with the resultant improvements in lung function, may allow for more rapid weaning from mechanical ventilation, leading to improved pulmonary outcomes, both short-term and long-term. Modifications to protocol being investigated.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16870913Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE; NO CLD Study Group. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006 Jul 27;355(4):343-53. doi: 10.1056/NEJMoa061088.
Background: PubMed 17671061Ballard PL, Merrill JD, Truog WE, Godinez RI, Godinez MH, McDevitt TM, Ning Y, Golombek SG, Parton LA, Luan X, Cnaan A, Ballard RA. Surfactant function and composition in premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Aug;120(2):346-53. doi: 10.1542/peds.2007-0095.
Background: PubMed 17403837Truog WE, Ballard PL, Norberg M, Golombek S, Savani RC, Merrill JD, Parton LA, Cnaan A, Luan X, Ballard RA; Nitric Oxide (to Prevent) Chronic Lung Disease Study Investigators. Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Apr;119(4):670-8. doi: 10.1542/peds.2006-2683.
Background: PubMed 23037875Keller RL, Merrill JD, Black DM, Steinhorn RH, Eichenwald EC, Durand DJ, Ryan RM, Truog WE, Courtney SE, Ballard PL, Ballard RA. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res. 2012 Dec;72(6):613-9. doi: 10.1038/pr.2012.136. Epub 2012 Oct 4.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Roberta A Ballard, MD principal investigator

University of California, San Francisco

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

SP-B Content (time frame: One day after dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00569530, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021.