Trial Outcomes & Findings for Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing (NCT NCT00626028)

NCT ID: NCT00626028

Last Updated: 2019-12-20

Results Overview

A composite of hemodynamic measurements were used to identify reversible pulmonary hypertension (vasoreactivity)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

136 participants

Primary outcome timeframe

on Day 1

Results posted on

2019-12-20

Participant Flow

Children scheduled for clinically indicated right heart catheterization were screened for enrollment at 16 centers in the United States, United Kingdom, France, Spain and Netherlands.

All 136 patients screened received all three study drugs in a crossover design, serving as their own controls. They were randomized 1:1 into two treatment sequences.

Participant milestones

Participant milestones
Measure
Nitric Oxide First, Oxygen Last
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Overall Study
STARTED
68
68
Overall Study
COMPLETED
62
59
Overall Study
NOT COMPLETED
6
9

Reasons for withdrawal

Reasons for withdrawal
Measure
Nitric Oxide First, Oxygen Last
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Overall Study
Adverse Event
1
1
Overall Study
Device Failure
0
1
Overall Study
Physician Decision
2
1
Overall Study
Inclusion/Exclusion Criteria
3
6

Baseline Characteristics

Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Nitric Oxide First, Oxygen Last
n=68 Participants
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=68 Participants
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Total
n=136 Participants
Total of all reporting groups
Age, Categorical
<=18 years
68 Participants
n=5 Participants
68 Participants
n=7 Participants
136 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
5.9 years
STANDARD_DEVIATION 5.58 • n=5 Participants
5.9 years
STANDARD_DEVIATION 5.58 • n=7 Participants
5.9 years
STANDARD_DEVIATION 5.58 • n=5 Participants
Sex: Female, Male
Female
34 Participants
n=5 Participants
34 Participants
n=7 Participants
68 Participants
n=5 Participants
Sex: Female, Male
Male
34 Participants
n=5 Participants
34 Participants
n=7 Participants
68 Participants
n=5 Participants
Region of Enrollment
France
30 participants
n=5 Participants
27 participants
n=7 Participants
57 participants
n=5 Participants
Region of Enrollment
United States
15 participants
n=5 Participants
17 participants
n=7 Participants
32 participants
n=5 Participants
Region of Enrollment
Spain
12 participants
n=5 Participants
12 participants
n=7 Participants
24 participants
n=5 Participants
Region of Enrollment
Netherlands
5 participants
n=5 Participants
6 participants
n=7 Participants
11 participants
n=5 Participants
Region of Enrollment
United Kingdom
6 participants
n=5 Participants
6 participants
n=7 Participants
12 participants
n=5 Participants

PRIMARY outcome

Timeframe: on Day 1

Population: All participants in the intent to treat analysis set who completed the study

A composite of hemodynamic measurements were used to identify reversible pulmonary hypertension (vasoreactivity)

Outcome measures

Outcome measures
Measure
Nitric Oxide First, Oxygen Last
n=62 Participants
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=59 Participants
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Number of Participants With Reversible Pulmonary Hypertension (Vasoreactivity)
28 Participants
16 Participants

SECONDARY outcome

Timeframe: within 1 year

Population: All participants in the intent to treat analysis set who completed the study

Number of participants who received surgery for pulmonary or cardiac disease within 1 year after treatment.

Outcome measures

Outcome measures
Measure
Nitric Oxide First, Oxygen Last
n=62 Participants
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=59 Participants
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Number of Participants With Related Surgical Procedures Within 1 Year
44 Participants
21 Participants

SECONDARY outcome

Timeframe: on Day 1

Population: All participants in the intent to treat analysis set who completed the study

An AE was defined as any untoward medical occurrence. An AE need not have a causal relationship with treatment and included any event that was not seen at baseline or, if present at baseline, increased in severity.

Outcome measures

Outcome measures
Measure
Nitric Oxide First, Oxygen Last
n=62 Participants
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=59 Participants
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Number of Participants With Adverse Events (AEs)
5 Participants
2 Participants

SECONDARY outcome

Timeframe: within 12 hours

Population: Participants in the intent to treat analysis set who completed the study

SAEs were collected during the 12 hours after discontinuation of gas or discharge (whichever came first). An SAE was defined as any event that resulted in death, was life threatening, resulted in permanent disability or incapacity, required or prolonged inpatient hospitalization, or was a congenital anomaly. Important medical events that, without medical or surgical intervention, would also have resulted in one of the outcomes listed above were also considered as SAEs.

Outcome measures

Outcome measures
Measure
Nitric Oxide First, Oxygen Last
n=62 Participants
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=59 Participants
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Number of Participants With Serious Adverse Events (SAEs)
3 Participants
0 Participants

SECONDARY outcome

Timeframe: within 3 years

Population: Participants in the intent to treat population who completed the study

Number of participants who received surgery related to pulmonary or cardiac disease within 3 years

Outcome measures

Outcome measures
Measure
Nitric Oxide First, Oxygen Last
n=62 Participants
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=59 Participants
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Number of Participants With Related Surgical Procedures Within 3 Years
12 Participants
6 Participants

Adverse Events

Nitric Oxide First, Oxygen Last

Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths

Oxygen First, Nitric Oxide Last

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Nitric Oxide First, Oxygen Last
n=62 participants at risk
10 minute dose of Nitric Oxide (NO) at 80 ppm, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of 100% Oxygen on Day 1.
Oxygen First, Nitric Oxide Last
n=59 participants at risk
10 minute dose of 100% Oxygen, then 10 minute dose of NO plus Oxygen, then 10 minute washout, then 10 minute dose of NO at 80 ppm on Day 1.
Investigations
ST Segment Elevation
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
Cardiac disorders
Bradycardia
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
Respiratory, thoracic and mediastinal disorders
Pulmonary Hypertension
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
Cardiac disorders
Cardiac Arrest
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
Vascular disorders
Hypotension
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
Cardiac disorders
Low Cardiac Output Syndrome
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
Investigations
Decreased oxygen saturation
1.6%
1/62 • Number of events 1 • within 3 years
No non-serious adverse events reached the 5% reporting threshold
0.00%
0/59 • within 3 years
No non-serious adverse events reached the 5% reporting threshold

Other adverse events

Adverse event data not reported

Additional Information

Medical Information Call Center

Mallinckrodt Pharmaceuticals

Phone: 800-556-3314

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER