Lung DiseasesPhase 3NCT00006401
Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants
A Phase 3 study testing iNO in people with Lung Diseases and Bronchopulmonary Dysplasia, run by University of Colorado, Denver at 14 sites in United States.
Trial summary
To determine whether or not inhaled nitric oxide (iNO) safely decreases the incidence of chronic lung disease (CLD) in premature infants. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Lung Diseases, Bronchopulmonary Dysplasia
- What is being tested?
- iNO
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 793 participants
- Where
- 14 sitesUnited States
- Study dates
- Sep 2000to Oct 2007
- 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 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Weighing between 500 to 1250 grams at birth
- Gestational age of less than 34 weeks
- Less than 48 hours old
- Respiratory failure on mechanical ventilation
- Absence of structural heart disease (PDA, ASD less than 1 cm, or VSD less than 2 mm are permitted if known prior to study entry)
- Absence of lethal congenital anomaly
Who cannot join
- Concurrent participation in another experimental study (observational studies will be allowed with prior approval by the Steering Committee and Data and Safety Monitoring Board)
- Active pulmonary hemorrhage
- Unevaluated pneumothorax
- High frequency jet ventilation
- Expected short duration of ventilation (less than 48 hours from birth)
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Children's Hospital
Denver, Colorado, 80218-1088
Duke University Medical Center
Durham, North Carolina, 27710
University of Connecticut Health Center
Farmington, Connecticut, 06030
University of Iowa Hospital & Clinics
Iowa City, Iowa, 52242
Loma Linda University Medical Center
Loma Linda, California, 92350
Univeristy of Southern California/Good Samaritan Hospital
Los Angeles, California, 90033
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Children's Hospital of Oklahoma
Oklahoma City, Oklahoma, 73104
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
St. Joseph's Hospital
Phoenix, Arizona, 85013
Magee-Women's Hospital
Pittsburgh, Pennsylvania, 15213
Utah Valley Regional Medical Center
Provo, Utah, 84604
About this study
Official title: Inhaled NO for the Prevention of Chronic Lung Disease
To determine whether or not inhaled nitric oxide (iNO) safely decreases the incidence of chronic lung disease (CLD) in premature infants.
Read the detailed description
BACKGROUND:
Despite advances in medical, nursing, and respiratory care, CLD affects up to 50 percent of premature infants. As a result, nearly 50,000 infants in the United States develop CLD. It is desirable to investigate therapies that decrease the incidence of CLD because it is associated with failure to thrive, developmental delay, increased risk of pulmonary infection, reactive airway disease, pulmonary hypertension, and death.
DESIGN NARRATIVE:
This is a randomized, double-blind, placebo-controlled, multi-center study. Three specific hypotheses will be tested: 1) iNO reduces the incidence of CLD; 2) iNO reduces serum and lung (tracheal aspirate) markers of inflammation; and 3) iNO does not increase the incidence of intraventricular hemorrhage in premature neonates. The primary endpoint is survival without CLD (defined as continued oxygen requirement) at 36 weeks post conceptional age.
A total of 793 premature newborns will be enrolled from 14 centers within 48 hours of birth. They will be randomly assigned to receive either placebo or iNO at 5 ppm until the breathing tube can be safely removed or after 21 days. The iNO will be delivered by an INOvent delivery system in such a way that physicians and nurses will not know which treatment each participant is receiving. Management strategies for aspects of patient care including mechanical ventilation, surfactant administration, fluid administration, and steroid use will be determined by physicians at each center. Serial cranial ultrasounds and methemoglobin levels will be monitored to determine adverse events. The first 200 patients will have serial blood samples and tracheal aspirates obtained for measurements of inflammatory mediators, including interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), endothelin-1, myeloperoxidase, neutrophil counts (tracheal aspirates), and endothelin-1 (blood). Participants will be seen at 12 and 24 months of age to monitor the long-term effects on the cardiopulmonary or neurologic systems. At these visits, a health questionnaire will be administered and Bayley II scales of infant development will be completed.
- Conditions
- Lung Diseases, Bronchopulmonary Dysplasia
- Being tested
- iNO, Placebo
- Medical subject headings
- Lung Diseases, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iNODrug
Also called Inhaled nitric oxide.
Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants
PlaceboOther
Inhaled Nitrogen
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide (iNO) | Experimental | Nitric Oxide study gas will be initiated at 5 ppm using the INOvent delivery system. The delivery system provides for masked delivery of the treatment gas. This dose will be used for a 21-day period or until extubation. Receives: Drug: iNO |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participant's survival without CLD
Measured: (measured at 36 weeks after birth)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2000 (estimated)
- Study startSep 2000
- Primary completionSep 2005
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lung DiseasesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 793 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- John P. Kinsella, MD, Study chair, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006401
- Sponsor's protocol ID
- 99-233
- Other IDs
- U01HL064857
- Status last verified
- Oct 2015
- First submitted
- 12 Oct 2000
- Last updated
- 6 Oct 2015
- Results posted
- No
Publications
Kinsella JP, Cutter GR, Walsh WF, Gerstmann DR, Bose CL, Hart C, Sekar KC, Auten RL, Bhutani VK, Gerdes JS, George TN, Southgate WM, Carriedo H, Couser RJ, Mammel MC, Hall DC, Pappagallo M, Sardesai S, Strain JD, Baier M, Abman SH. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med. 2006 Jul 27;355(4):354-64. doi: 10.1056/NEJMoa060442.
PubMed 16870914Mourani PM, Kinsella JP, Clermont G, Kong L, Perkins AM, Weissfeld L, Cutter G, Linde-Zwirble WT, Abman SH, Angus DC, Watson RS; Prolonged Outcomes after Nitric Oxide (PrONOx) Investigators. Intensive care unit readmission during childhood after preterm birth with respiratory failure. J Pediatr. 2014 Apr;164(4):749-755.e3. doi: 10.1016/j.jpeds.2013.11.062. Epub 2013 Dec 31.
PubMed 24388320Watson RS, Clermont G, Kinsella JP, Kong L, Arendt RE, Cutter G, Linde-Zwirble WT, Abman SH, Angus DC; Prolonged Outcomes After Nitric Oxide Investigators. Clinical and economic effects of iNO in premature newborns with respiratory failure at 1 year. Pediatrics. 2009 Nov;124(5):1333-43. doi: 10.1542/peds.2009-0114. Epub 2009 Oct 19.
PubMed 19841128
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled NO for the Prevention of Chronic Lung Disease
- ClinicalTrials.gov ID
- NCT00006401
- Acronym / sponsor ID
- 99-233
- Conditions
- Lung Diseases, Bronchopulmonary Dysplasia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 793 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2000
- Primary completion
- Sep 2005 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 13 Oct 2000 (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.
To determine whether or not inhaled nitric oxide (iNO) safely decreases the incidence of chronic lung disease (CLD) in premature infants.
Detailed description
BACKGROUND:
Despite advances in medical, nursing, and respiratory care, CLD affects up to 50 percent of premature infants. As a result, nearly 50,000 infants in the United States develop CLD. It is desirable to investigate therapies that decrease the incidence of CLD because it is associated with failure to thrive, developmental delay, increased risk of pulmonary infection, reactive airway disease, pulmonary hypertension, and death.
DESIGN NARRATIVE:
This is a randomized, double-blind, placebo-controlled, multi-center study. Three specific hypotheses will be tested: 1) iNO reduces the incidence of CLD; 2) iNO reduces serum and lung (tracheal aspirate) markers of inflammation; and 3) iNO does not increase the incidence of intraventricular hemorrhage in premature neonates. The primary endpoint is survival without CLD (defined as continued oxygen requirement) at 36 weeks post conceptional age.
A total of 793 premature newborns will be enrolled from 14 centers within 48 hours of birth. They will be randomly assigned to receive either placebo or iNO at 5 ppm until the breathing tube can be safely removed or after 21 days. The iNO will be delivered by an INOvent delivery system in such a way that physicians and nurses will not know which treatment each participant is receiving. Management strategies for aspects of patient care including mechanical ventilation, surfactant administration, fluid administration, and steroid use will be determined by physicians at each center. Serial cranial ultrasounds and methemoglobin levels will be monitored to determine adverse events. The first 200 patients will have serial blood samples and tracheal aspirates obtained for measurements of inflammatory mediators, including interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), endothelin-1, myeloperoxidase, neutrophil counts (tracheal aspirates), and endothelin-1 (blood). Participants will be seen at 12 and 24 months of age to monitor the long-term effects on the cardiopulmonary or neurologic systems. At these visits, a health questionnaire will be administered and Bayley II scales of infant development will be completed.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide (iNO) | Experimental | Drug: iNONitric Oxide study gas will be initiated at 5 ppm using the INOvent delivery system. The delivery system provides for masked delivery of the treatment gas. This dose will be used for a 21-day period or until extubation. |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Weighing between 500 to 1250 grams at birth
- Gestational age of less than 34 weeks
- Less than 48 hours old
- Respiratory failure on mechanical ventilation
- Absence of structural heart disease (PDA, ASD less than 1 cm, or VSD less than 2 mm are permitted if known prior to study entry)
Key exclusion criteria (5 listed)
- Concurrent participation in another experimental study (observational studies will be allowed with prior approval by the Steering Committee and Data and Safety Monitoring Board)
- Active pulmonary hemorrhage
- Unevaluated pneumothorax
- High frequency jet ventilation
- Expected short duration of ventilation (less than 48 hours from birth)
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 |
|---|---|---|
| iNOAlso: Inhaled nitric oxide.Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants | Drug | Inhaled Nitric Oxide (iNO) |
| PlaceboInhaled Nitrogen | Other | Placebo |
Primary outcome
Participant's survival without CLD
Time frame: (measured at 36 weeks after birth)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2015.
- Results publication: PubMed 16870914Kinsella JP, Cutter GR, Walsh WF, Gerstmann DR, Bose CL, Hart C, Sekar KC, Auten RL, Bhutani VK, Gerdes JS, George TN, Southgate WM, Carriedo H, Couser RJ, Mammel MC, Hall DC, Pappagallo M, Sardesai S, Strain JD, Baier M, Abman SH. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med. 2006 Jul 27;355(4):354-64. doi: 10.1056/NEJMoa060442.
- Derived from this study: PubMed 24388320Mourani PM, Kinsella JP, Clermont G, Kong L, Perkins AM, Weissfeld L, Cutter G, Linde-Zwirble WT, Abman SH, Angus DC, Watson RS; Prolonged Outcomes after Nitric Oxide (PrONOx) Investigators. Intensive care unit readmission during childhood after preterm birth with respiratory failure. J Pediatr. 2014 Apr;164(4):749-755.e3. doi: 10.1016/j.jpeds.2013.11.062. Epub 2013 Dec 31.
- Derived from this study: PubMed 19841128Watson RS, Clermont G, Kinsella JP, Kong L, Arendt RE, Cutter G, Linde-Zwirble WT, Abman SH, Angus DC; Prolonged Outcomes After Nitric Oxide Investigators. Clinical and economic effects of iNO in premature newborns with respiratory failure at 1 year. Pediatrics. 2009 Nov;124(5):1333-43. doi: 10.1542/peds.2009-0114. Epub 2009 Oct 19.
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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.
John P. Kinsella, MD study chair
Children's Hospital Medical Center, Cincinnati
14 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 iNO in people with Lung Diseases and Bronchopulmonary Dysplasia, run by University of Colorado, Denver at 14 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 6 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: finished, as of the sponsor's last update on 6 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Participant's survival without CLD (time frame: (measured at 36 weeks after birth)). 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 NCT00006401, which also lists 3 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 6 Oct 2015.