Trial Outcomes & Findings for Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises (NCT NCT00094887)
NCT ID: NCT00094887
Last Updated: 2020-02-05
Results Overview
VOC resolution was defined by all of the following conditions: * Pain relief - Visual Analog Scale (VAS) pain scores of 6 or less, (6 as worst and 0 as best) * Freedom from parenteral narcotic use, * Ability to walk unless the subject was not able to walk for any reason other than acute VOC prior to the onset of crisis, * Subject and/or family's belief that the painful crisis could be managed at home with or without oral analgesic use, and the physician concurred with that assessment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
150 participants
Primary outcome timeframe
within 30 days
Results posted on
2020-02-05
Participant Flow
Participants were recruited from 11 study centers in the United States
Of the 150 participants recruited, 150 were randomized (1:1) into treatment groups.
Participant milestones
| Measure |
Inhaled Nitric Oxide
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
Participants receive Nitrogen gas
|
|---|---|---|
|
Overall Study
STARTED
|
75
|
75
|
|
Overall Study
Safety Population
|
75
|
75
|
|
Overall Study
Intent to Treat Population
|
75
|
75
|
|
Overall Study
Per Protocol Analysis Set
|
71
|
71
|
|
Overall Study
Primary Efficacy Population
|
65
|
64
|
|
Overall Study
COMPLETED
|
71
|
71
|
|
Overall Study
NOT COMPLETED
|
4
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises
Baseline characteristics by cohort
| Measure |
Inhaled Nitric Oxide
n=75 Participants
Inhaled Nitric Oxide INO
|
Placebo
n=75 Participants
Nitrogen gas
|
Total
n=150 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 16 years
|
12 participants
n=5 Participants
|
14 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Age, Customized
>=16 years
|
63 participants
n=5 Participants
|
61 participants
n=7 Participants
|
124 participants
n=5 Participants
|
|
Age, Continuous
|
26.6 years
STANDARD_DEVIATION 11.06 • n=5 Participants
|
26.0 years
STANDARD_DEVIATION 10.49 • n=7 Participants
|
26.3 years
STANDARD_DEVIATION 10.75 • n=5 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
75 participants
n=5 Participants
|
75 participants
n=7 Participants
|
150 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: within 30 daysPopulation: Primary efficacy analysis set, defined as intent to treat population with VOC resolution
VOC resolution was defined by all of the following conditions: * Pain relief - Visual Analog Scale (VAS) pain scores of 6 or less, (6 as worst and 0 as best) * Freedom from parenteral narcotic use, * Ability to walk unless the subject was not able to walk for any reason other than acute VOC prior to the onset of crisis, * Subject and/or family's belief that the painful crisis could be managed at home with or without oral analgesic use, and the physician concurred with that assessment.
Outcome measures
| Measure |
Inhaled Nitric Oxide
n=65 Participants
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
n=64 Participants
Participants receive Nitrogen gas
|
|---|---|---|
|
Time to Vaso-occlusive Pain Crisis (VOC) Resolution
|
61.83 Hours
Interval 9.93 to 412.17
|
55.16 Hours
Interval 8.0 to 233.0
|
SECONDARY outcome
Timeframe: within 40 daysPopulation: Intention to treat
Length of hospitalization is defined as the length of time from admission to discharge order
Outcome measures
| Measure |
Inhaled Nitric Oxide
n=75 Participants
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
n=75 Participants
Participants receive Nitrogen gas
|
|---|---|---|
|
Length of Hospitalization
|
4.06 Days
Interval 0.76 to 21.35
|
3.11 Days
Interval 0.05 to 39.02
|
SECONDARY outcome
Timeframe: within 24 hoursPopulation: Intention to treat
Outcome measures
| Measure |
Inhaled Nitric Oxide
n=75 Participants
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
n=75 Participants
Participants receive Nitrogen gas
|
|---|---|---|
|
Number of Participants Discharged to Home Within the First 24 Hours
|
5 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: within 8 hours and within 40 daysPopulation: Intention to treat
The total dose (mg) of opioid medications received during the trial
Outcome measures
| Measure |
Inhaled Nitric Oxide
n=75 Participants
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
n=75 Participants
Participants receive Nitrogen gas
|
|---|---|---|
|
Total Dose of Opioids Received
within 8 hours
|
16.25 mg
Interval 0.0 to 196.5
|
17.25 mg
Interval 0.0 to 440.0
|
|
Total Dose of Opioids Received
within 40 days
|
153.75 mg
Interval 1.6 to 3117.8
|
211.37 mg
Interval 2.0 to 7506.2
|
SECONDARY outcome
Timeframe: within 40 daysPopulation: Intention to treat
Number of participants who required a blood transfusion before discharge because of acute chest syndrome/pneumonia
Outcome measures
| Measure |
Inhaled Nitric Oxide
n=75 Participants
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
n=75 Participants
Participants receive Nitrogen gas
|
|---|---|---|
|
Number of Participants With Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion
|
8 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: during first 24 hours and during 30 day follow-upPopulation: Intention to treat
The number of participants readmitted to the hospital for any reason within 30 days after discharge
Outcome measures
| Measure |
Inhaled Nitric Oxide
n=75 Participants
Participants receive Inhaled Nitric Oxide (INO)
|
Placebo
n=75 Participants
Participants receive Nitrogen gas
|
|---|---|---|
|
Number of Participants Readmitted to Hospital Within 30 Days After Discharge
during first 24 hours
|
0 Participants
|
0 Participants
|
|
Number of Participants Readmitted to Hospital Within 30 Days After Discharge
during 30-day follow-up
|
9 Participants
|
17 Participants
|
Adverse Events
Inhaled Nitric Oxide
Serious events: 7 serious events
Other events: 35 other events
Deaths: 0 deaths
Placebo
Serious events: 6 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Inhaled Nitric Oxide
n=75 participants at risk
Inhaled Nitric Oxide INO
|
Placebo
n=75 participants at risk
Nitrogen gas
|
|---|---|---|
|
Blood and lymphatic system disorders
Acute Chest Syndrome
|
6.7%
5/75 • Number of events 5
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
6.7%
5/75 • Number of events 5
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Gastrointestinal disorders
Dysphagia
|
1.3%
1/75 • Number of events 1
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
0.00%
0/75
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Investigations
Hemoglobin Decrease
|
1.3%
1/75 • Number of events 1
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
0.00%
0/75
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
General disorders
Pyrexia
|
1.3%
1/75 • Number of events 1
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
1.3%
1/75 • Number of events 1
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
General disorders
Sensation of Foreign Body
|
1.3%
1/75 • Number of events 1
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
0.00%
0/75
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
Other adverse events
| Measure |
Inhaled Nitric Oxide
n=75 participants at risk
Inhaled Nitric Oxide INO
|
Placebo
n=75 participants at risk
Nitrogen gas
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.7%
5/75 • Number of events 5
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
5.3%
4/75 • Number of events 4
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Gastrointestinal disorders
Constipation
|
2.7%
2/75 • Number of events 2
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
5.3%
4/75 • Number of events 4
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Nervous system disorders
Headache
|
4.0%
3/75 • Number of events 3
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
6.7%
5/75 • Number of events 5
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Gastrointestinal disorders
Nausea
|
6.7%
5/75 • Number of events 5
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
5.3%
4/75 • Number of events 4
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
5.3%
4/75 • Number of events 4
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
8.0%
6/75 • Number of events 6
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
General disorders
Pyrexia
|
16.0%
12/75 • Number of events 13
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
13.3%
10/75 • Number of events 10
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
5/75 • Number of events 5
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
1.3%
1/75 • Number of events 2
75 subjects were assigned to treatment with iNO and 75 subjects were assigned to treatment with placebo; all subjects were included in the ITT and Safety Populations. 142 subjects completed the study according to the protocol and 8 subjects (4 in each treatment group) did not complete the study according to protocol.
|
Additional Information
Medical Information Call Center
Mallinckrodt Pharmaceuticals
Phone: 800-556-3314
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER