Registry to Evaluate INOmax in Newborn Babies With Pulmonary Hypertension (PaTTerN)

Multicenter, Prospectively Defined Observational Registry With Retrospective Data Collection, Evaluating Premature and Term-Near-Term Neonates With Pulmonary Hypertension Receiving Inhaled Nitric Oxide Via Invasive or Noninvasive Ventilation

Pulmonary hypertension is high blood pressure in the arteries to the lungs. It is a serious condition. It causes the blood vessels that carry blood from the heart to the lungs to become hard and narrow. When this happens, the heart has to work harder to pump the blood through.

Some babies are born with pulmonary hypertension (PH). Doctors might use INOmax (a gas the baby breathes) to help newborn babies (neonates) with PH. This study will use information from the records of registered babies to see how effective and safe INOmax is for treating premature and other newborn babies for up to 11 days after they are born.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension of Newborn
• Intervention / Treatment: Drug: INOmax

• Study Type: Observational
• Enrollment (Actual): 140

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital Research Institute
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care
    • Long Beach, California, United States, 90801
      • Miller Children's and Women's Hospital - Long Beach
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women and Newborns
    • San Francisco, California, United States, 94143
      • UCSF Benioff Children's Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale New Haven Children's Hospital
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital for Children
    • Tampa, Florida, United States, 33620
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comer Children's Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Stead Family Children's Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Chandler
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Amplatz Children's Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis Children's Hospital
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Children's Hospital of New Jersey at Newark Beth Israel Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Rainbow Babies & Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The Children's Hospital at OU Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 9 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Premature (P) and term-near-term (TNT) neonates

Description

Inclusion Criteria:

1. Was either a P neonate born at least 27 weeks to less than 34 weeks of gestational age (GA) or a TNT neonate born at least 34 weeks but no more than 40 weeks of GA.
2. Was administered INOmax therapy after birth to 7 days of age via any route (invasive or noninvasive ventilation) for a minimum treatment period of at least 24 hours up to 96 ± 12 hours. The participants may receive INOmax for a longer period.
3. Had PH, as confirmed by echocardiogram or a differential saturation gradient of at least 10%.
4. Received INOmax administration as part of routine clinical practice in a Level III or higher neonatal intensive care unit in the United States.
5. Has all variables required to calculate OI or SOI (a baseline sample prior to treatment and 4 samples obtained during treatment).

Exclusion Criteria:

1. Was at risk of imminent death (death expected within 24 hours).
2. Received extracorporeal membrane oxygenation (ECMO).
3. Had a life-threatening abnormality (cranial, cardiac, thoracic), chromosomal abnormality, congenital diaphragmatic hernia, congenital heart defect (other than patent ductus arteriosus or small atrial septal defect).
4. Had been resuscitated requiring chest compressions within 6 hours of receiving INOmax.
5. Had Grade IV bilateral intraventricular hemorrhage or periventricular leukomalacia.
6. Had active uncontrolled bleeding.
7. Had disseminated intravascular coagulopathy.
8. Had active seizures while receiving anticonvulsants.
9. Experienced prolonged asphyxia with evidence of severe acidosis (pH < 7.25).
10. Received concomitant pulmonary vasodilator therapy (eg, prostacyclin or sildenafil) except when sildenafil was used to wean the participant from INOmax therapy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
P Neonates; Premature (P) neonates [at least 27 weeks but less than 34 weeks of gestational age]	Drug: INOmax; Nitric oxide gas for inhalation provided via mechanical ventilation or non invasive ventilation
TNT Neonates; Term-Near-Term (TNT) neonates at least 34 weeks of gestational age	Drug: INOmax; Nitric oxide gas for inhalation provided via mechanical ventilation or non invasive ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of neonates with significant response to INOmax treatment within each age group	Significant response is defined as at least a 25% improvement from baseline in oxygenation index or surrogate oxygenation index (OI/SOI) during INOMAX treatment	within 108 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of neonates with significant response to Inomax treatment within each age group and severity group	The severity of pulmonary hypertension (PH) is classified for each participant Categories: Mild, Moderate, Severe	within 108 hours
Time to reach significant response to Inomax treatment within each age group and severity group	The median time to INOmax complete response (25% improvement) for neonates with each baseline PH severity classification Categories: Mild, Moderate, Severe	within 108 hours
Number of neonates with partial response to INOmax treatment within each age group and severity group	Partial response is defined as less than a 25% improvement in OI/SOI during INOmax treatment	within 108 hours

Collaborators and Investigators

• Sponsor: Mallinckrodt

Publications and helpful links

General Publications

• Nelin L, Kinsella JP, Courtney SE, Pallotto EK, Tarau E, Potenziano JL. Use of inhaled nitric oxide in preterm vs term/near-term neonates with pulmonary hypertension: results of the PaTTerN registry study. J Perinatol. 2022 Jan;42(1):14-18. doi: 10.1038/s41372-021-01252-x. Epub 2021 Oct 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2017
• Primary Completion (ACTUAL): February 11, 2020
• Study Completion (ACTUAL): February 11, 2020

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (ACTUAL): April 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2020
• Last Update Submitted That Met QC Criteria: June 16, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Premature and term-near-term neonates
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: MNK19050056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No