Inhaled Iloprost as an Adjunct to Inhaled Nitric Oxide in Pediatric Critical Care Patients

A Randomized, Double Blind, Placebo-controlled Pilot Study of the Safety and Effective Dosing of Inhaled Iloprost in Pediatric Patients With Pulmonary Hypertension Treated With Inhaled Nitric Oxide

The purpose of this study is to determine whether inhaled iloprost is safe and effective in pediatric patients with pulmonary hypertension who are sick in the intensive care unit.

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Hypertension; Acute Respiratory Distress Syndrome; Congenital Heart Defects; Neonatal Hypoxic Respiratory Failure; Persistent Pulmonary Hypertension of Newborn
• Intervention / Treatment: Drug: Iloprost; Drug: Placebo

Detailed Description

Inhaled nitric oxide (NO) is used in the management of all causes of pediatric pulmonary hypertension. Despite widespread use of nitric oxide to treat critically ill mechanically-ventilated pediatric patients with pulmonary hypertension, response to therapy is not universal. Nitric oxide fails to improve oxygenation in approximately 30% of these patients. Nonresponders to nitric oxide have few treatment options. Iloprost is the only other medication approved for inhalational delivery in the treatment of pulmonary hypertension. Inhalation therapy for pulmonary vasodilatation in critically ill children is inherently more attractive than oral or intravenous therapies due to the ability to deliver medication directly to the lung and to decrease systemic effects. The use of inhaled iloprost has been reported to decrease pulmonary vascular resistance in many pediatric pathologic settings, including combination therapy with nitric oxide.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Birth to 21 years of age

• Diagnosis of pulmonary hypertension must fit into one of three categories

  • neonatal hypoxic respiratory failure
  • congenital heart disease
  • acquired/acute respiratory distress syndrome (lung disease)
• Parents of subject must be able and willing to give written informed consent and comply with the requirements of the study protocol and must authorize release and use of protected health information
• Patients who remain on nitric oxide at 12 to 18 hours after initiation
• Patients who are transferred to an intensive care unit already on inhaled nitric oxide from another institution will be treated as if nitric oxide therapy was started at the time of admission to the unit
• Patients will be enrolled only after a clinical decision to treat with nitric oxide has been made by the treating physician

Exclusion Criteria:

• Corrected gestational age less than 35 weeks
• Patients with potentially fatal non-cardiopulmonary co-morbidities (e.g. hepatic, neurologic, renal)
• Known or suspected fatal genetic syndrome
• Patient with cardiac failure secondary to significant left-sided obstructive lesions
• Patient on ECMO
• Patient on any other form of prostacyclin
• Patient on any medication with known NO production, e.g., nitroprusside
• Patient on an endothelin receptor antagonist (e.g. bosentan)
• Patient on sildenafil
• Patient on whom clinicians do not agree to follow standard inhaled nitric oxide weaning protocol
• Patients who have known hypersensitivity to prostacyclin or any of its components
• Patient who is pregnant
• Patient with platelet count less than 50,000

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhaled Iloprost	Drug: Iloprost; Inhaled via Aerogen nebulizer, 0.5 mcg/kg every 2 hours; uptitrated to effect, to maximum dose of 30 mcg every 30 minutes; Other Names: Ventavis
Placebo Comparator: Inhaled Placebo	Drug: Placebo; Inhaled via Aerogen nebulizer, 0.5 mcg/kg every 2 hours or more

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and effective dosing of inhaled iloprost in mechanically ventilated pediatric patients with pulmonary hypertension.	For the duration of time that the subject is receiving the study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to wean off iNO.	When the participant is successfully weaned off study drug
Time to extubation.	When the participant is successfully weaned off study drug
Total cost of iNO.	When the participant is successfully weaned off study drug
Incidence of rebound phenomenon, as defined by the need to return to a higher iNO dose after a previous wean.	When the participant is successfully weaned off study drug
Time to ICU discharge	When the participant is successfully weaned off study drug.

Collaborators and Investigators

• Sponsor: Seattle Children's Hospital
• Collaborators: Actelion
• Investigators: Principal Investigator: Delphine Yung, MD, Seattle Children's Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: September 18, 2009
• First Submitted That Met QC Criteria: September 21, 2009
• First Posted (Estimate): September 22, 2009

Study Record Updates

• Last Update Posted (Estimate): January 19, 2015
• Last Update Submitted That Met QC Criteria: January 15, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Iloprost; Nitric oxide; Mechanical ventilator
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Lung Injury; Cardiovascular Abnormalities; Infant, Premature, Diseases; Hypertension; Respiratory Insufficiency; Hypertension, Pulmonary; Persistent Fetal Circulation Syndrome; Heart Defects, Congenital; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: SCIL-001-12806