Trial Outcomes & Findings for Treprostinil Sodium Inhalation for Patients At High Risk for ARDS (NCT NCT02370095)

NCT ID: NCT02370095

Last Updated: 2019-10-01

Results Overview

PaO2/FiO2 ratio

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: Change in PaO2/FiO2 ratio from day 0 to day 2.
• Results posted on: 2019-10-01

Participant Flow

One patient was consented, randomized (Placebo) and baseline data was collected. However, before receiving treatment the subject deteriorated, and a protocol defined stopping rule was met. The subject was defined as completed. Baseline data were used in the analyses, and the AEs recorded are presented in the AE section.

Participant milestones

Measure	Treprostinil Inhalation Solution Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Overall Study STARTED	10	4
Overall Study COMPLETED	10	3
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Treprostinil Inhalation Solution Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Treprostinil Sodium Inhalation for Patients At High Risk for ARDS

Baseline characteristics by cohort

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil	Total n=14 Participants Total of all reporting groups
Age, Continuous	49.2 years STANDARD_DEVIATION 13.1 • n=5 Participants	51.8 years STANDARD_DEVIATION 7.6 • n=7 Participants	50.0 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized African-American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change in PaO2/FiO2 ratio from day 0 to day 2.

Population: Determination of this endpoint was dependent on subject consent for collection of an arterial blood sample. A baseline measure was obtained from thirteen subjects. Samples were obtained from seven subjects at day 2, and two subjects at day 7 and none at day 28. Analysis was limited to change from baseline to day 2.

PaO2/FiO2 ratio

Outcome measures

Measure	Treprostinil Inhalation Solution n=5 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=1 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Change in the Ratio of the Partial Pressure of Arterial Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)	55.6 P/F ratio Standard Error 31.2	161.1 P/F ratio Standard Error 0

SECONDARY outcome

Timeframe: 0-12 days

Population: Intent to treat

SaO2/FiO2

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Change in the Ratio of Peripheral Oxygen Saturation to Fraction of Inspired Oxygen (SaO2/FiO2)	303.7 S/F ratio Standard Error 22.0	382.3 S/F ratio Standard Error 36.9

SECONDARY outcome

Timeframe: 0-28 days post enrollment

Ventilator-free days

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Number of Days Not on a Ventilator	16.4 days Standard Deviation 14.1	28 days Standard Deviation 0

SECONDARY outcome

Timeframe: 0-28 days

Population: Intent to treat

BiPAP / CPAP

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Number of Subjects Who Required Bi-level Positive Airway Pressure (BiPAP) or Continuous Positive Airway Pressure (CPAP) Via Face Mask	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Change from day 0 on days 3 and 7

Population: Too few samples were collected at the designated days 3 and 7 to provide informative data. Plasma samples were not analyzed.

Change in ARDS associated plasma biomarkers

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change in SCVO2 from Day 0 to 3 (if central venous catheter in place)

Population: None of the patients had a central venous line, so no samples were obtained for analysis.

SCVO2

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change in CVP from Day 0 to 3 (if central venous catheter in place)

Population: A central venous line was not in place for the subjects so measurements could not be obtained

CVP

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change in MAP from Day 0 to day 7

Population: Intent to Treat

MAP

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Change in Mean Arterial Pressure (MAP).	-9.96 mm Hg Standard Deviation 15.5	8.18 mm Hg Standard Deviation 13.1

SECONDARY outcome

Timeframe: 0-28 days

All-cause mortality

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
All-cause Mortality	4 Participants	0 Participants

SECONDARY outcome

Timeframe: 0-28 days

Population: Intent to treat

Intubation / Mechanical Ventilation

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Number of Subjects Requiring Intubation and Mechanical Ventilation	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Deaths during hospitalization (up to 3 months)

Population: Intent to Treat

Hospital Mortality

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Number of Deaths During Hospitalization	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 3

Population: Only 3 plasma pharmacokinetic samples were collected from subjects treated with Treprostinil and therefore no measurements of plasma Treprostinil were made.

Treprostinil Plasma Concentration

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 0 to day 28

Population: Intent to Treat

Time to intubation and mechanical ventilation

Outcome measures

Measure	Treprostinil Inhalation Solution n=10 Participants Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 Participants Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Number of Days From Study Enrollment Until Mechanical Ventilation is Required	2.8 days Standard Deviation 2.2	0 days Standard Deviation 0

Adverse Events

Treprostinil Inhalation Solution

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treprostinil Inhalation Solution n=10 participants at risk Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 participants at risk Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Respiratory, thoracic and mediastinal disorders Death	40.0% 4/10 • Number of events 4 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Infections and infestations septic shock	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Immune system disorders Transfusion Reaction	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.

Other adverse events

Measure	Treprostinil Inhalation Solution n=10 participants at risk Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days. Treprostinil Inhalation Solution: Treprostinil inhalation solution administered as blinded marketed product	Placebo n=4 participants at risk Placebo administration will be administered as above for the active arm Placebo: Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Gastrointestinal disorders Nausea/Emesis	30.0% 3/10 • Number of events 3 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Gastrointestinal disorders Cholelithiasis	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Respiratory, thoracic and mediastinal disorders Metapneumovirus	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Respiratory, thoracic and mediastinal disorders Pneumomediatinum/Bilateral pneumothoraces	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Injury, poisoning and procedural complications Retro-peritoneal hematoma	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Gastrointestinal disorders Hematemesis	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Vascular disorders Hypertension	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Gastrointestinal disorders Ileus	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Renal and urinary disorders Renal Failure	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
General disorders Sleep Interference	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Renal and urinary disorders Hematuria	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Respiratory, thoracic and mediastinal disorders Wheezing	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Renal and urinary disorders Acute Kidney Injury	20.0% 2/10 • Number of events 2 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Renal and urinary disorders Hypernatremia	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	25.0% 1/4 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.
Immune system disorders Transfusion Reaction	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Gastrointestinal disorders GI Bleed	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Respiratory, thoracic and mediastinal disorders Hypoxemia	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Cardiac disorders Hypotension	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Renal and urinary disorders Hyponatremia	10.0% 1/10 • Number of events 2 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Gastrointestinal disorders Elevated Transaminase	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Respiratory, thoracic and mediastinal disorders Parapneuomonic Effusion with decortication	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.	0.00% 0/4 • From time of enrollment until end of follow-up, approximately 28 days.
Nervous system disorders Delirium	0.00% 0/10 • From time of enrollment until end of follow-up, approximately 28 days.	25.0% 1/4 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.
Blood and lymphatic system disorders Hyperbilirubinemia	0.00% 0/10 • From time of enrollment until end of follow-up, approximately 28 days.	25.0% 1/4 • Number of events 1 • From time of enrollment until end of follow-up, approximately 28 days.

Additional Information

Wayne H Anderson, PhD

University of North Carolina at Chapel Hill

Phone: 919-445-0351

Email: wayne_anderson@med.unc.edu

Results disclosure agreements

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