Infant, NewbornPhase 3Preemie iNONCT00016523

Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure

A Phase 3 study testing Inhaled nitric oxide in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 17 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This multicenter trial tested whether inhaled nitric oxide would reduce death or the need for oxygen in preterm infants (less than 34 weeks gestational age) with severe lung disease. Read more about this study

Who is it for?: Ages Up to 120 hours
Conditions the study is for: Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
What is being tested?: Inhaled nitric oxide
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 420 participants
Where: 17 sitesUnited States
Study dates: Jan 2001to May 2006
Phase: Phase 3
Are there results?: None posted in the registry

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 Up to 120 hours
All sexes
No healthy volunteers
Child

Who may be able to join

Any infant with a birth weight 401 - 1500 grams and < 34 weeks gestational age with an OI (mean Paw x FiO2 x 100/PaO2) > 10 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.
or
Infants > 1500 grams and < 34 weeks gestational age will be entered in the Larger Preemie Pilot Study if they have an OI greater than or equal to 15 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.
Infants requiring assisted ventilation with a diagnosis of RDS/HMD, pneumonia and/or sepsis, aspiration syndrome, idiopathic pulmonary hypertension, or suspected pulmonary hypoplasia associated with PROM and/or oligohydramnios.
Greater than or equal to 4 hours after one dose of surfactant.
Less than or equal to 120 hours of age.
All infants must have an indwelling arterial line.

Who cannot join

Any infant in whom a decision has been made not to provide full treatment (e.g. chromosomal anomalies or severe birth asphyxia).
Known structural congenital heart disease, except patent ductus arteriosus and atrial-level shunts.
Infants with any major abnormality involving the respiratory system such as congenital diaphragmatic hernia, tracheoesophageal fistula or cystic fibrosis.
Any bleeding diathesis considered to be clinically significant or thrombocytopenia with platelet count < 50,000.
Prior enrollment into a conflicting clinical trial such as the Neonatal Network Surfactant CPAP trial.Inclusion Criteria

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

United States17 sites

University of Alabama at Birmingham
Birmingham, Alabama, 35233
Wake Forest University
Charlotte, North Carolina, 27157
Northwestern University
Chicago, Illinois, 60614
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Florida
Jacksonville, Florida, 32209
University of Miami
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of California at San Diego
San Diego, California, 92103-8774

Other trials in United States

About this study

This multicenter trial tested whether inhaled nitric oxide would reduce death or the need for oxygen in preterm infants (less than 34 weeks gestational age) with severe lung disease.

Read the detailed description

This multicenter, randomized, double-masked, controlled clinical trial evaluated the efficacy of inhaled nitric oxide (iNO) in the treatment of the preterm infant with respiratory failure secondary to respiratory distress syndrome (RDS), sepsis/pneumonia, aspiration syndrome, idiopathic pulmonary hypertension and/or suspected pulmonary hypoplasia.

Infants were followed until death or discharge to home. The trial compared iNO therapy to mock gas delivery as the control, and otherwise incorporated conventional management strategies (including treatment with surfactant and high frequency ventilation as adjuncts to iNO therapy).

During the initial dosing, iNO was started at 5 ppm and could be increased to 10 ppm. If the infant did not respond, study gas was discontinued. For infants who responded to study gas, a gradual weaning was initiated. The total exposure to study gas did not exceed 336 hours (14 days). Infants were monitored for signs of toxicity.

Medical and neurodevelopmental outcome of surviving infants were assessed at 18 to 22 months corrected age by masked, certified examiners.

Conditions: Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Respiratory Distress Syndrome (RDS), Sepsis
Being tested: Inhaled nitric oxide, Placebo
Keywords: NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Very Low Birth Weight (VLBW), Prematurity, Inhaled nitric oxide, Aspiration syndrome, Idiopathic pulmonary hypertension, Pulmonary hypoplasia
Medical subject headings: Premature Birth, Respiratory Distress Syndrome, Sepsis, Pneumonia, Hypertension, Pulmonary, Familial Primary Pulmonary Hypertension

What participants receive

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

Inhaled nitric oxideDrug
Started at 5 ppm and could be increased to 10 ppm
PlaceboDrug
Started at 5 ppm and could be increased to 10 ppm

Study groups in NCT00016523
Study group	Role	What they receive
Inhaled Nitric Oxide	Experimental	Inhaled Nitric Oxide Receives: Drug: Inhaled nitric oxide
Placebo	Active comparator	Inhaled Oxygen Receives: Drug: Placebo

What is being measured

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

Death or Bronchopulmonary Dysplasia
Measured: At 36 weeks post-conceptional age

Secondary outcomes (8)

Intraventricular Hemorrhage Grade III and IV
Measured: At 36 weeks post-conceptional age
Days on assisted ventilation
Measured: At 36 weeks post-conceptional age
Length of hospitalization
Measured: At hospital discharge
Retinopathy of prematurity
Measured: At hospital discharge
Air leaks
Measured: At 36 weeks post-conceptual age
Days on oxygen
Measured: At 36 weeks post-conceptual age
Supplemental oxygen
Measured: At 36 weeks post-conceptual age
Neurodevelopmental outcome
Measured: 18-22 months corrected age

Timeline

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

Jan 2001May 2006

First posted16 May 2001 (estimated)
Study startJan 2001
Primary completionSep 2003
Study completionMay 2006

Why it stopped: Preliminary results showed increased intraventricular hemorrhage (IVH) in experimental arm

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Infant, NewbornStudies 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: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 420 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00016523
Sponsor's protocol ID: NICHD-NRN-0026
Other IDs: U10HD034216, M01RR000032, U10HD027904, U10HD027853, M01RR008084, U10HD027856, M01RR000750, U10HD021397
Acronym: Preemie iNO
Status last verified: Sep 2017
First submitted: 14 May 2001
Last updated: 26 Sep 2017
Results posted: No
Data monitoring committee: Yes

Publications

Sokol GM, Ehrenkranz RA. Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes. Semin Perinatol. 2003 Aug;27(4):311-9. doi: 10.1016/s0146-0005(03)00043-0.
PubMed 14510322
Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Higgins RD, Oh W, Hudak ML, Laptook AR, Shankaran S, Finer NN, Carlo WA, Kennedy KA, Fridriksson JH, Steinhorn RH, Sokol GM, Konduri GG, Aschner JL, Stoll BJ, D'Angio CT, Stevenson DK; Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med. 2005 Jul 7;353(1):13-22. doi: 10.1056/NEJMoa043927.
PubMed 16000352
Van Meurs KP, Hintz SR, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Das A, Higgins RD, Stevenson DK. Inhaled nitric oxide in infants >1500 g and <34 weeks gestation with severe respiratory failure. J Perinatol. 2007 Jun;27(6):347-52. doi: 10.1038/sj.jp.7211690. Epub 2007 Apr 19.
PubMed 17443204
Hintz SR, Slovis T, Bulas D, Van Meurs KP, Perritt R, Stevenson DK, Poole WK, Das A, Higgins RD; NICHD Neonatal Research Network. Interobserver reliability and accuracy of cranial ultrasound scanning interpretation in premature infants. J Pediatr. 2007 Jun;150(6):592-6, 596.e1-5. doi: 10.1016/j.jpeds.2007.02.012.
PubMed 17517240
Hintz SR, Van Meurs KP, Perritt R, Poole WK, Das A, Stevenson DK, Ehrenkranz RA, Lemons JA, Vohr BR, Heyne R, Childers DO, Peralta-Carcelen M, Dusick A, Johnson YR, Morris B, Dillard R, Vaucher Y, Steichen J, Adams-Chapman I, Konduri G, Myers GJ, de Ungria M, Tyson JE, Higgins RD; NICHD Neonatal Research Network. Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide. J Pediatr. 2007 Jul;151(1):16-22, 22.e1-3. doi: 10.1016/j.jpeds.2007.03.017.
PubMed 17586184
Ambalavanan N, Van Meurs KP, Perritt R, Carlo WA, Ehrenkranz RA, Stevenson DK, Lemons JA, Poole WK, Higgins RD; NICHD Neonatal Research Network, Bethesda, MD. Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure. J Perinatol. 2008 Jun;28(6):420-6. doi: 10.1038/jp.2008.18. Epub 2008 Mar 13.
PubMed 18337740
Chock VY, Van Meurs KP, Hintz SR, Ehrenkranz RA, Lemons JA, Kendrick DE, Stevenson DK; NICHD Neonatal Research Network. Inhaled nitric oxide for preterm premature rupture of membranes, oligohydramnios, and pulmonary hypoplasia. Am J Perinatol. 2009 Apr;26(4):317-22. doi: 10.1055/s-0028-1104743. Epub 2008 Dec 9.
PubMed 19067285

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Infant, Newborn trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure
ClinicalTrials.gov ID: NCT00016523
Acronym / sponsor ID: Preemie iNO / NICHD-NRN-0026
Conditions: Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Respiratory Distress Syndrome (RDS), Sepsis
Keywords: NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Very Low Birth Weight (VLBW), Prematurity, Inhaled nitric oxide, Aspiration syndrome, Idiopathic pulmonary hypertension, Pulmonary hypoplasia
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Preliminary results showed increased intraventricular hemorrhage (IVH) in experimental arm
Enrolment: 420 participants (actual)
Lead sponsor: NICHD Neonatal Research NetworkResearch network
Collaborators: National Center for Research Resources (NCRR)
Study start: Jan 2001
Primary completion: Sep 2003 (actual)
Study completion: May 2006 (actual)
First posted: 16 May 2001 (estimated)
Results: Not posted in the source record

Clinical summary

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

This multicenter trial tested whether inhaled nitric oxide would reduce death or the need for oxygen in preterm infants (less than 34 weeks gestational age) with severe lung disease.

Detailed description

Medical and neurodevelopmental outcome of surviving infants were assessed at 18 to 22 months corrected age by masked, certified examiners.

Study design

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

Arm	Type	Receives
Inhaled Nitric Oxide	Experimental	Drug: Inhaled nitric oxideInhaled Nitric Oxide
Placebo	Active comparator	Drug: PlaceboInhaled Oxygen

Who may qualify

Ages: Up to 120 hours
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

Any infant with a birth weight 401 - 1500 grams and < 34 weeks gestational age with an OI (mean Paw x FiO2 x 100/PaO2) > 10 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.
or
Infants > 1500 grams and < 34 weeks gestational age will be entered in the Larger Preemie Pilot Study if they have an OI greater than or equal to 15 on two consecutive blood gases at least 30 minutes apart, but no more than 12 hours apart.
Infants requiring assisted ventilation with a diagnosis of RDS/HMD, pneumonia and/or sepsis, aspiration syndrome, idiopathic pulmonary hypertension, or suspected pulmonary hypoplasia associated with PROM and/or oligohydramnios.
Greater than or equal to 4 hours after one dose of surfactant.

Key exclusion criteria (5 listed)

Any infant in whom a decision has been made not to provide full treatment (e.g. chromosomal anomalies or severe birth asphyxia).
Known structural congenital heart disease, except patent ductus arteriosus and atrial-level shunts.
Infants with any major abnormality involving the respiratory system such as congenital diaphragmatic hernia, tracheoesophageal fistula or cystic fibrosis.
Any bleeding diathesis considered to be clinically significant or thrombocytopenia with platelet count < 50,000.
Prior enrollment into a conflicting clinical trial such as the Neonatal Network Surfactant CPAP trial.Inclusion Criteria

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
Inhaled nitric oxideStarted at 5 ppm and could be increased to 10 ppm	Drug	Inhaled Nitric Oxide
PlaceboStarted at 5 ppm and could be increased to 10 ppm	Drug	Placebo

Primary outcome

Death or Bronchopulmonary Dysplasia
Time frame: At 36 weeks post-conceptional age

8 secondary outcomes

Intraventricular Hemorrhage Grade III and IV
Time frame: At 36 weeks post-conceptional age
Days on assisted ventilation
Time frame: At 36 weeks post-conceptional age
Length of hospitalization
Time frame: At hospital discharge
Retinopathy of prematurity
Time frame: At hospital discharge
Air leaks
Time frame: At 36 weeks post-conceptual age
Days on oxygen
Time frame: At 36 weeks post-conceptual age
Supplemental oxygen
Time frame: At 36 weeks post-conceptual age
Neurodevelopmental outcome
Time frame: 18-22 months corrected age

Results and safety

The study was stopped early (reason given: Preliminary results showed increased intraventricular hemorrhage (IVH) in experimental arm). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2017.
Background: PubMed 14510322Sokol GM, Ehrenkranz RA. Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes. Semin Perinatol. 2003 Aug;27(4):311-9. doi: 10.1016/s0146-0005(03)00043-0.
Results publication: PubMed 16000352Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Higgins RD, Oh W, Hudak ML, Laptook AR, Shankaran S, Finer NN, Carlo WA, Kennedy KA, Fridriksson JH, Steinhorn RH, Sokol GM, Konduri GG, Aschner JL, Stoll BJ, D'Angio CT, Stevenson DK; Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med. 2005 Jul 7;353(1):13-22. doi: 10.1056/NEJMoa043927.
Results publication: PubMed 17443204Van Meurs KP, Hintz SR, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Das A, Higgins RD, Stevenson DK. Inhaled nitric oxide in infants >1500 g and <34 weeks gestation with severe respiratory failure. J Perinatol. 2007 Jun;27(6):347-52. doi: 10.1038/sj.jp.7211690. Epub 2007 Apr 19.
Results publication: PubMed 17517240Hintz SR, Slovis T, Bulas D, Van Meurs KP, Perritt R, Stevenson DK, Poole WK, Das A, Higgins RD; NICHD Neonatal Research Network. Interobserver reliability and accuracy of cranial ultrasound scanning interpretation in premature infants. J Pediatr. 2007 Jun;150(6):592-6, 596.e1-5. doi: 10.1016/j.jpeds.2007.02.012.
Results publication: PubMed 17586184Hintz SR, Van Meurs KP, Perritt R, Poole WK, Das A, Stevenson DK, Ehrenkranz RA, Lemons JA, Vohr BR, Heyne R, Childers DO, Peralta-Carcelen M, Dusick A, Johnson YR, Morris B, Dillard R, Vaucher Y, Steichen J, Adams-Chapman I, Konduri G, Myers GJ, de Ungria M, Tyson JE, Higgins RD; NICHD Neonatal Research Network. Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide. J Pediatr. 2007 Jul;151(1):16-22, 22.e1-3. doi: 10.1016/j.jpeds.2007.03.017.
Results publication: PubMed 18337740Ambalavanan N, Van Meurs KP, Perritt R, Carlo WA, Ehrenkranz RA, Stevenson DK, Lemons JA, Poole WK, Higgins RD; NICHD Neonatal Research Network, Bethesda, MD. Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure. J Perinatol. 2008 Jun;28(6):420-6. doi: 10.1038/jp.2008.18. Epub 2008 Mar 13.
Results publication: PubMed 19067285Chock VY, Van Meurs KP, Hintz SR, Ehrenkranz RA, Lemons JA, Kendrick DE, Stevenson DK; NICHD Neonatal Research Network. Inhaled nitric oxide for preterm premature rupture of membranes, oligohydramnios, and pulmonary hypoplasia. Am J Perinatol. 2009 Apr;26(4):317-22. doi: 10.1055/s-0028-1104743. Epub 2008 Dec 9.
NICHD Neonatal Research NetworkLink provided by the sponsor.

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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.

Krisa P. Van Meurs, MD study director

Stanford University

Waldemar A. Carlo, MD principal investigator

University of Alabama at Birmingham

Abbot R. Laptook, MD principal investigator

Brown University, Women & Infants Hospital of Rhode Island

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inhaled nitric oxide in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 17 sites in United States.

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 7 inclusion and 5 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: stopped early, as of the sponsor's last update on 26 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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. 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?

The study was stopped early (reason given: Preliminary results showed increased intraventricular hemorrhage (IVH) in experimental arm). Results are not available in the source record.

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?

Death or Bronchopulmonary Dysplasia (time frame: At 36 weeks post-conceptional age). 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 NCT00016523, which also lists 7 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 26 Sep 2017.