A Phase 3 interventional study of Nitric oxide and Placebo in Lung Disease, sponsored by Mallinckrodt. Completed at 35 sites in 9 countries. Open to participants aged Up to 26 Hours. Per ClinicalTrials.gov, last updated 2021-02-05.
Sponsored by Mallinckrodt · Phase 3, Interventional, and Treatment
The purpose of this study is to assess the safety and efficacy of inhaled nitric oxide to reduce the risk of chronic lung disease in pre-term infants with respiratory distress, and to assess the long-term effects of the therapy on the development of these children over 7 years of clinical follow-up.
Although the effects of inhaled Nitric Oxide on pulmonary vascular tone are well-described and relevant to term infants with persistent pulmonary hypertension, the pathophysiology of respiratory failure in preterm infants may be quite different. Chronic lung disease (CLD) represents the final pathway of a heterogeneous group of pulmonary disorders of infancy that usually start in the neonatal period. CLD most commonly occurs in preterm (\<30 weeks of gestational age (GA) infants with birth weights less than 1,500 grams (g), and especially in those very preterm (\<26 weeks GA) with birth weights less than 1,000 g, and who have been treated for respiratory distress syndrome (RDS).
3,319 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.
This study's enrollment of 800 is above the median of 71 across 2,122 interventional studies indexed under Lung Diseases.
Browse Lung Diseases studies →Mallinckrodt is the lead sponsor of 87 studies on the registry; none are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 15 (100%) have results posted.
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Exclusion Criteria:
INO administered by nasal continuous positive airway pressure, nasal cannula or face mask at 5 parts per million (ppm) for between 7 and 21 days
Drug: Nitric oxide
Placebo gas administered by nasal continuous positive airway pressure, nasal cannula or face mask, for a maximum of 21 days.
Drug: Placebo
Nitric Oxide vapour (gas) for inhalation (400 ppm)
Also known as: INO max®
Placebo gas for inhalation
Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress
Survival without BPD is defined as the number of preterm infants of 36 weeks gestational age who survived the treatment period without the need for supplemental oxygen
Time frame: 21 days
Mortality at 7-year Follow-up
Number of participants who died between 2 years and the 7-year Follow-up Period
Time frame: at 7-year Follow-up
Strengths and Difficulties Questionnaire Results for Participants at 7-year Follow-up
The Strengths and Difficulties Questionnaire contained 25 questions that were used to create 5 scales (ranging from 10=most normal to 0=most abnormal) for emotional symptoms, conduct problems, hyperactivity, peer problems, and (10=most abnormal, 0=most normal) for prosocial.
Time frame: At 7-year Follow-up
Thirty-five Medical Centers participated and enrolled a total of 800 participants (Intent to treat population).
| Milestone | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| Started | 399 | 401 |
| Safety population | 395 | 397 |
| Completed | 338 | 338 |
| Not completed | 61 | 63 |
| Withdrew: Protocol deviation | 6 | 11 |
| Withdrew: Delivery device failure | 1 | 3 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Death | 33 | 31 |
| Withdrew: Inclusion/exclusion criteria | 4 | 4 |
| Withdrew: Adverse event | 15 | 12 |
| Withdrew: Withdrawal by subject | 2 | 1 |
| Milestone | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| Started | 152 | 153 |
| Completed | 152 | 153 |
| Not completed | 0 | 0 |
Survival without BPD is defined as the number of preterm infants of 36 weeks gestational age who survived the treatment period without the need for supplemental oxygen
| Participants | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| Survival Without Bronchopulmonary Dysplasia (BPD) in Preterm Infants With Respiratory Distress | 258 | 262 |
Number of participants who died between 2 years and the 7-year Follow-up Period
| Participants | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| Mortality at 7-year Follow-up | 0 | 0 |
The Strengths and Difficulties Questionnaire contained 25 questions that were used to create 5 scales (ranging from 10=most normal to 0=most abnormal) for emotional symptoms, conduct problems, hyperactivity, peer problems, and (10=most abnormal, 0=most normal) for prosocial.
| score on a scale | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| Emotional (0=most normal, 10=most abnormal) | 1.9 ± 1.79 | 2.1 ± 1.96 |
| Conduct (0=most normal, 10=most abnormal) | 1.4 ± 1.55 | 1.4 ± 1.58 |
| Hyperactivity (0=most normal, 10=most abnormal) | 3.8 ± 2.64 | 3.4 ± 2.66 |
| Peer problems (0=most normal, 10=most abnormal) | 1.2 ± 1.41 | 1.5 ± 1.74 |
| Prosocial (10=most abnormal, 0=most normal) | 8.6 ± 1.73 | 8.4 ± 1.81 |
Collected over Adverse events (AEs), including clinically significant changes in vital signs, oxygen saturation, and laboratory values, were collected in the safety population for a maximum of 21 days (not during follow-up). All serious AEs are listed, and non-serious treatment-emergent adverse events (TEAEs) are listed if 5% or more participants in any arm experienced any form of that preferred term within 21 days. Survival was counted through the 7-year follow-up, and included under All-cause Mortality.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Inhaled Nitric Oxide (INO) | 56/395 (14.2%) | 170/395 (43%) | 358/395 (90.6%) |
| Placebo | 48/397 (12.1%) | 177/397 (44.6%) | 334/397 (84.1%) |
| Event | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| Patent ductus arteriosusCongenital, familial and genetic disorders | 62/395 | 54/397 |
| Haemorrhage intracranialNervous system disorders | 50/395 | 42/397 |
| SepsisInfections and infestations | 34/395 | 35/397 |
| Intestinal perforationGastrointestinal disorders | 17/395 | 14/397 |
| Necrotising enterocolitis neonatalGastrointestinal disorders | 16/395 | 9/397 |
| Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders | 12/395 | 14/397 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 12/395 | 13/397 |
| Periventricular leukomalaciaNervous system disorders | 7/395 | 2/397 |
| HydrocephalusNervous system disorders | 4/395 | 4/397 |
| HypotensionVascular disorders | 4/395 | 1/397 |
| Event | Inhaled Nitric Oxide (INO) | Placebo |
|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 189/395 | 168/397 |
| Patent ductus arteriosusCongenital, familial and genetic disorders | 183/395 | 158/397 |
| HyperbilirubinaemiaHepatobiliary disorders | 122/395 | 120/397 |
| JaundiceHepatobiliary disorders | 98/395 | 89/397 |
| HyperglycaemiaMetabolism and nutrition disorders | 90/395 | 68/397 |
| ApnoeaRespiratory, thoracic and mediastinal disorders | 73/395 | 78/397 |
| Haemorrhage intracranialNervous system disorders | 73/395 | 55/397 |
| SepsisInfections and infestations | 68/395 | 60/397 |
| HypotensionVascular disorders | 55/395 | 50/397 |
| Metabolic acidosisMetabolism and nutrition disorders | 49/395 | 52/397 |
| Age, Customized(Participants) | Inhaled Nitric Oxide (INO) | Placebo | Total |
|---|---|---|---|
| Preterm newborn infants (gestational age < 37 wks) | 399 | 401 | 800 |
| Sex: Female, Male(Participants) | Inhaled Nitric Oxide (INO) | Placebo | Total |
|---|---|---|---|
| Female | 192 | 181 | 373 |
| Male | 207 | 220 | 427 |
Plan to share: No — Discussion of statistical endpoints and analysis are included in manuscripts. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT00551642) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.
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Studies of the drug tested here: Nitric Oxide