Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia

Pulmonary Hypertension Clinical Trial

Official title:

Treatment of Delayed Pulmonary Transition in Extremely Preterm Infants & Bronchopulmonary Dysplasia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03576885
• Other study ID #: 1170748
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 15, 2019
• Est. completion date: December 1, 2024

Study information

• Verified date: June 2023
• Source: AdventHealth
• Contact: Hussnain Mirza, MD
• Phone: 407-303-2528
• Email: hussnain.mirza.md[@]flhosp.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Inhaled nitric oxide (iNO) is an effective treatment for pulmonary hypertension (PH) in term and near-term infants. Preterm infants are at risk for early PH that is associated with high risk for bronchopulmonary dysplasia or death. In multiple clinical trials, iNO treatment was not effective for BPD prevention. However, infants were not screened for PH and iNO treatment was not targeted for PH. iNO treatment for PH in preterm infants is controversial due to lack of evidence. The study team hypothesizes that early diagnosis of PH (72-96 hours of life) and iNO treatment will decrease the incidence of death and bronchopulmonary dysplasia and improve oxygenation in extremely preterm infants.

1. To determine if iNO treatment of extremely preterm infants with early pulmonary hypertension as established with echocardiographic evidence at 72-96 hours of age will decrease incidence of death or BPD.

2. To determine if iNO treatment of extremely preterm infants with early PH will decrease the pulmonary artery pressure and improve oxygenation within 72 hours of intervention.

Description:

This is a single center, blinded, randomized control clinical trial to evaluate the effects of inhaled nitric oxide on the outcome of survival and incidence of bronchopulmonary dysplasia. This trial has a planned enrollment of 138 infants with 68 infants with delayed pulmonary transition assigned to either the treatment or placebo group. There is no enrollment restriction based on gender, ethnicity, or race. Enrollment is expected to take 36 months with an additional 12 months for data analysis.Infants with early pulmonary hypertension will be randomized to the treatment or placebo group. Treatment will continue until resolution of pulmonary hypertension or through Day 14, whichever comes first. Serial echocardiograms will be performed every 48 hours +/-12 hours until Day 14. Oxygen saturation levels will be averaged every 24 hour period following enrollment. This study will provide evidence for the beneficial effects of early diagnosis and treatment of pulmonary hypertension in preterm infants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 29 Weeks

Eligibility

Inclusion Criteria:

Step 1:

• Birth between 23 weeks and 0 days and 29 weeks and 6 days.

• Positive pressure ventilation at 72-96 hours of age

Step 2:

• Early pulmonary hypertension

Exclusion Criteria:

Step 1:

• Death prior to 12 hours of age or first echocardiogram

• Chromosomal anomalies

• Major congenital anomalies

• Myocardial dysfunction

• Complex cardiac defect

• Dependent on right to left shunting of blood

Step 2:

• Excessive pulmonary blood flow (left to right shunt across PDA)

• Pulmonary blood flow obstruction secondary to pulmonary vein stenosis

• Mitral valve stenosis

• Cor triata

• Aortic valve atresia

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• inhaled nitric oxide
inhaled nitric oxide will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension
• Placebo
placebo will be administered starting at 20 ppm. Treatment will continue for 14 days or until resolution of pulmonary hypertension

Locations

Country	Name	City	State
United States	AdventHealth	Orlando	Florida

Sponsors (3)

Lead Sponsor	Collaborator
AdventHealth	Mallinckrodt, Thrasher Research Fund

Country where clinical trial is conducted

United States, 

References & Publications (30)

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Kinsella JP, Steinhorn RH, Krishnan US, Feinstein JA, Adatia I, Austin ED, Rosenzweig EB, Everett AD, Fineman JR, Hanna BD, Hopper RK, Humpl T, Ivy DD, Keller RL, Mullen MP, Raj JU, Wessel DL, Abman SH. Recommendations for the Use of Inhaled Nitric Oxide Therapy in Premature Newborns with Severe Pulmonary Hypertension. J Pediatr. 2016 Mar;170:312-4. doi: 10.1016/j.jpeds.2015.11.050. Epub 2015 Dec 15. No abstract available. — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death (yes/no)	Incidence of death	36 weeks post menstrual age
Primary	Bronchopulmonary (BPD) dysplasia (yes/no)	Incidence of bronchopulmonary dysplasia as determined by need for positive pressure ventilation or supplemental oxygen after room air challenge test	36 weeks post menstrual age
Secondary	Pulmonary arterial pressure (mmHg)	Pulmonary arterial pressure will be averaged for each 24-48 hour period after enrollment	Duration of treatment or up to Day 14
Secondary	Oxygen saturation level percentage	Oxygen saturation level will be averaged for each 24 hour period after enrollment	Duration of treatment or up to Day 14
Secondary	SF (SpO2/FiO2) ratio	Pulse oximetric saturation Spo2/Fio2 ratio	Duration of treatment or up to Day 14