Nitric Oxide Administration for Acute Respiratory Distress Syndrome

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT00240487
• Collaborator: Mallinckrodt (Industry)
• Enrollment: 52
• Location: 1
• Arms: 2
• Duration (Months): 96
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This research project is an open-label, randomized study for the use of Nitric Oxide in pediatric patients with acute respiratory distress syndrome (ARDS). The study examines whether nitric oxide (NO) treatment impacts the the P:F ratio (arterial partial pressure of oxygen (PaO2) divided by fraction of inspired oxygen (FiO2) in patients with ARDS. The goal of the study is to evaluate whether the order of NO therapy will have any effect on response, and evaluate the characteristics of patients who respond to NO compared to those who do not.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome	Drug: Nitric Oxide; Other: No Intervention	Phase 3

Detailed Description

At low concentrations, nitric oxide(NO) functions as a cellular messenger and regulator of microcirculation. NO may have an important role in the pathogenesis of ARDS as well as its treatment. NO may be primarily useful in improving matching of ventilation and perfusion in the lung. The aims of the study are to attempt to show that NO will improve oxygenation as evidenced by improvement in PaO2/FiO2. Secondary aims are to see if the improvement in oxygenation allows there to be decreased time on FiO2>0.60, evaluate whether the order of NO therapy will have any effect on response, and evaluate the characteristics of patients who respond to NO compared to those who do not.

Subjects will be randomized to receive either nitric oxide first (nitric oxide for the first 4 hours, then no intervention/no nitric oxide for the next 4 hours) or delayed treatment with nitric oxide (no intervention/no nitric oxide for the first 4 hours, then nitric oxide for the next 4 hours)..

Blood gases were monitored once an hour during study participation (total of 8 hours). Final PaO2/FiO2 levels will be compared after 8 hours of study treatment in each group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Nitric Oxide Administration for Acute Respiratory Distress Syndrome
• Study Start Date: Sep 1, 2000
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nitric oxide first Subjects will be randomized to receive Nitric Oxide (NO) immediately after study entry, given at 10 parts per million (ppm) for the first 4 hours of study participation. Blood gases will be monitored once an hour for 4 hours. After the first 4 hours of study participation, the nitric oxide (NO) will be turned off and subjects will receive no intervention (no nitric oxide) for the next 4 hours of study participation. During this time, all subjects will receive standard clinical are. Blood gases will be monitored once an hour for 4 hours.	Drug: Nitric Oxide; Subjects will receive inhaled Nitric Oxide at a dose of 10 parts per million (ppm) for a 4 hour study period. Blood gases will be collected once an hour.; Other Names: Inhaled Nitric Oxide ; Other: No Intervention; Subjects will receive no intervention (i.e., no nitric oxide treatment) for a 4 hour study period. Blood gases will be collected once an hour. During this time, all subjects will receive standard clinical care.
Active Comparator: Delayed nitric oxide Subjects will be randomized to receive no intervention (no nitric oxide) for he first 4 hours of study participation. During this time, all subjects will receive standard clinical care. Blood gases will be monitored once an hour for 4 hours. After the first 4 hours of study participation, the nitric oxide will be turned on and subjects will receive 10 ppm of nitric oxide for the next 4 hours of study participation. Blood gases will be monitored once an hour for 4 hours.	Drug: Nitric Oxide; Subjects will receive inhaled Nitric Oxide at a dose of 10 parts per million (ppm) for a 4 hour study period. Blood gases will be collected once an hour.; Other Names: Inhaled Nitric Oxide ; Other: No Intervention; Subjects will receive no intervention (i.e., no nitric oxide treatment) for a 4 hour study period. Blood gases will be collected once an hour. During this time, all subjects will receive standard clinical care.

Outcome Measures

Primary Outcome Measures

1. Mean PaO2/FiO2 Ratio [8 hours]

   Arterial blood gas measurements with cooximetry to evaluate arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio. The mean PaO2/FiO2 ratio for each group after completion 8 hour of study participation was compared

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is intubated and mechanically ventilated in the Pediatric Intensive Care Unit with a PaO2/FiO2 ratio less than or equal to 100, FiO2 greater than or equal to 0.60, PEEP greater than or equal to 10, and a Murray score greater than or equal to 2.5.

Exclusion Criteria:

• Neonates (1 week to 28 days) and/or patients on extracorporeal membrane oxygenation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia
• Mallinckrodt

Investigators

• Principal Investigator: Rodolfo I Godinez, MD, PhD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT00240487
• Other Study ID Numbers: 2000-9-2088
• First Posted: Oct 18, 2005
• Last Update Posted: Apr 24, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Children's Hospital of Philadelphia: Acute Respiratory Distress Syndrome; ARDS; Nitric Oxide
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Nitric Oxide

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the Pediatric Intensive Care Unit from 2000-2008.

Arm/Group Title	Nitric Oxide First	Delayed Nitric Oxide
Arm/Group Description	Subjects who were randomized to receive Nitric Oxide (NO) began receiving NO immediately after study entry, given at 10 parts per million (ppm) for the first 4 hours of study participation. Blood gases were monitored once an hour for 4 hours. After the first four hours of study participation, the NO was turned off and subjects received no intervention (no nitric oxide) for the next 4 hours of study participation. Blood gases were monitored once an hour for 4 hours. After the initial 8 hours of study participation, subjects remained on whichever intervention (no intervention versus 10 ppm nitric oxide) they responded best to.	Subjects who were randomized to receive delayed treatment with Nitric Oxide (NO) began the first 4 hours of study participation receiving no intervention (no nitric oxide). Blood gases were monitored once an hour for 4 hours. After the first four hours of study participation, the NO was turned on and subjects received 10 ppm of nitric oxide for the next 4 hours of study participation. Blood gases were monitored once an hour for 4 hours.
Period Title: Overall Study
STARTED	24	28
COMPLETED	24	28
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Nitric Oxide First	Delayed Nitric Oxide	Total
Arm/Group Description	Subjects received 10 ppm nitric oxide for the first 4 hours of study participation After which, the NO was turned off and subjects received no intervention (no nitric oxide) for the next 4 hours of study participation. After the initial 8 hours of study participation, subjects will remain on whichever intervention (no nitric oxide versus 10 ppm nitric oxide) they responded best to.	Subjects received no intervention (no nitric oxide) for the first 4 hours of study participation. After which, they received 10 ppm nitric oxide for the next 4 hours of study participation. After the initial 8 hours of study participation, subjects will remain on whichever intervention (no nitric oxide versus 10 ppm nitric oxide) they responded best to.	Total of all reporting groups
Overall Participants	24	28	52
Age (Count of Participants)
<=18 years	24 100%	28 100%	52 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.93 (6.79)	8.06 (6.28)	8.84 (6.5)
Sex: Female, Male (Count of Participants)
Female	10 41.7%	14 50%	24 46.2%
Male	14 58.3%	14 50%	28 53.8%
Region of Enrollment (participants) [Number]
United States	24 100%	28 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Mean PaO2/FiO2 Ratio
Description	Arterial blood gas measurements with cooximetry to evaluate arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio. The mean PaO2/FiO2 ratio for each group after completion 8 hour of study participation was compared
Time Frame	8 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immediate Nitric Oxide Treatment	Delayed Nitric Oxide Treatment
Arm/Group Description	Subjects who were randomized to receive immediate treatment with nitric oxide (NO) began receiving NO immediately after study entry, given at 10 parts per million (ppm) for the first 4 hours of study participation. Blood gases were monitored once an hour for 4 hours. After the first four hours of study participation, the nitric oxide (NO) was turned off and subjects received no intervention (no nitric oxide) for the next 4 hours of study participation. During this time, all subjects received treatment standard clinical care. Blood gases were monitored once an hour for 4 hours.	Subjects who were randomized to receive delayed treatment with Nitric Oxide (NO) began the first 4 hours of study participation receiving no intervention (no nitric oxide). During this time, all subjects received standard clinical care. Blood gases were monitored once an hour for 4 hours. After the first four hours of study participation, the nitric oxide (NO) was turned on and subjects received 10 ppm of nitric oxide for the next 4 hours of study participation. Blood gases were monitored once an hour for 4 hours.
Measure Participants	24	28
Mean (Standard Deviation) [mmHg]	115.6 (40.6)	115.9 (40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Nitric Oxide Treatment, Delayed Nitric Oxide Treatment
	Comments	Differences in mean PaO2/FiO2 ratios between the two groups will help to determine whether order of therapy (immediate treatment with nitric oxide versus delayed treatment with nitric oxide) impacts outcomes.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The primary outcome variable is the mean PaO2/FiO2 in each group after 8 hours of study participation to determine whether timing of treatment with nitric oxide impacts outcome (immediate treatment versus delayed treatment).
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	All subjects were followed for 8 hours during study participation.
Arm/Group Title	Immediate Treatment With Nitric Oxide		Delayed Treatment With Nitric Oxide
Arm/Group Description	Subjects who were randomized to receive immediate treatment with nitric oxide (NO) began receiving NO immediately after study entry, given at 10 parts per million (ppm) for the first 4 hours of study participation. Blood gases were monitored once an hour for 4 hours. After the first four hours of study participation, the nitric oxide (NO) was turned off and subjects received no intervention (no nitric oxide) for the next 4 hours of study participation. During this time, all subjects received standard clinical care. Blood gases were monitored once an hour for 4 hours.		Subjects who were randomized to receive delayed treatment with Nitric Oxide (NO) began the first 4 hours of study participation receiving no intervention (no nitric oxide). During this time, all subjects received standard clinical care. Blood gases were monitored once an hour for 4 hours. After the first four hours of study participation, the NO was turned on and subjects received 10 ppm of nitric oxide for the next 4 hours of study participation. Blood gases were monitored once an hour for 4 hours.
All Cause Mortality
	Immediate Treatment With Nitric Oxide		Delayed Treatment With Nitric Oxide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Immediate Treatment With Nitric Oxide		Delayed Treatment With Nitric Oxide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Immediate Treatment With Nitric Oxide		Delayed Treatment With Nitric Oxide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/28 (0%)

Limitations/Caveats

There may be some confounding of effects of lung recruitment from high mean airway pressures over the duration of the observation period.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.