Trial Outcomes & Findings for LIPS-B: Lung Injury Prevention Study With Budesonide and Beta (NCT NCT01783821)

NCT ID: NCT01783821

Last Updated: 2016-09-05

Results Overview

Oxygen saturation (SpO2) was measured by pulse oximetry. FiO2 is the assumed proportion of oxygen concentration participating in gas exchange in the alveoli. All S/F measurements were performed per standard operating protocol using a Venturi mask titrated to obtain an oxygen saturation of 94 ± 2% unless the patient met this goal on room air or clinical status dictated an alternative delivery mode. This outcome measure was analyzed as a longitudinal continuous variable by a mixed effect model. The formula for the calculation of SpO2/FiO2 (or S/F ratio) is %saturation/proportion of FiO2 concentration.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 61 participants
• Primary outcome timeframe: baseline to day 5 after the first treatment
• Results posted on: 2016-09-05

Participant Flow

Subjects were enrolled from September 2013 to June 2015.

Participant milestones

Measure	Budesonide and Formoterol Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Overall Study STARTED	30	31
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Budesonide and Formoterol Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Overall Study Screen Failure	1	1

Baseline Characteristics

LIPS-B: Lung Injury Prevention Study With Budesonide and Beta

Baseline characteristics by cohort

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.	Total n=59 Participants Total of all reporting groups
Age, Continuous	71 years n=5 Participants	57 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants	30 participants n=7 Participants	59 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline to day 5 after the first treatment

Population: Intention to Treat analysis. The patient population for each day is indicated in the category by (treatment arm, placebo arm).

Oxygen saturation (SpO2) was measured by pulse oximetry. FiO2 is the assumed proportion of oxygen concentration participating in gas exchange in the alveoli. All S/F measurements were performed per standard operating protocol using a Venturi mask titrated to obtain an oxygen saturation of 94 ± 2% unless the patient met this goal on room air or clinical status dictated an alternative delivery mode. This outcome measure was analyzed as a longitudinal continuous variable by a mixed effect model. The formula for the calculation of SpO2/FiO2 (or S/F ratio) is %saturation/proportion of FiO2 concentration.

Outcome measures

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio Day 1 (29, 30)	376 SpO2/FiO2 Ratio Interval 320.0 to 448.0	336 SpO2/FiO2 Ratio Interval 269.0 to 448.0
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio Day 2 (25, 27)	400 SpO2/FiO2 Ratio Interval 343.0 to 457.0	332 SpO2/FiO2 Ratio Interval 245.0 to 396.0
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio Day 0 (29, 30)	320 SpO2/FiO2 Ratio Interval 258.0 to 343.0	334 SpO2/FiO2 Ratio Interval 269.0 to 380.0
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio Day 3 (17, 24)	396 SpO2/FiO2 Ratio Interval 336.0 to 448.0	360 SpO2/FiO2 Ratio Interval 267.5 to 450.0
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio Day 4 (13,19)	448 SpO2/FiO2 Ratio Interval 438.0 to 452.0	336 SpO2/FiO2 Ratio Interval 243.0 to 448.0
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio Day 5 (6,7)	375 SpO2/FiO2 Ratio Interval 263.0 to 448.0	362 SpO2/FiO2 Ratio Interval 248.0 to 452.0

PRIMARY outcome

Timeframe: Days 0 - 5

Population: Intention to Treat Analysis

The data in the table below represent the greatest change from baseline observed for any one participant over all individual post-baseline measurements.

Outcome measures

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Number of Participants Experiencing Categorical Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio >20% Decrease	0 participants	8 participants
Number of Participants Experiencing Categorical Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio No change (within 20%)	11 participants	9 participants
Number of Participants Experiencing Categorical Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio > 20% Increase	18 participants	13 participants

SECONDARY outcome

Timeframe: Hospital discharge, approximately day 28

Outcome measures

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Number of Subjects Who Needed Mechanical Ventilation	6 participants	16 participants

SECONDARY outcome

Timeframe: Hospital discharge, approximately day 28

ARDS was defined per Berlin definition. Chest radiographs of all ventilated (non-invasive or invasive) patients were reviewed as consistent or not consistent with ARDS by the site investigator. A second adjudication was performed by an alternate principal investigator blinded to subject identification and clinical data. Final diagnosis of ARDS was determined centrally after chest radiograph adjudication was considered together with other relevant clinical data.

Outcome measures

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Number of Subjects Who Developed Acute Respiratory Distress Syndrome (ARDS)	0 participants	7 participants

SECONDARY outcome

Timeframe: Baseline to Day 28

Outcome measures

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Hospital Length of Stay	4 days Interval 3.0 to 7.0	8 days Interval 4.0 to 15.0

SECONDARY outcome

Timeframe: Baseline to Day 28

Outcome measures

Measure	Budesonide and Formoterol n=29 Participants Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 Participants Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Intensive Care Unit (ICU) Length of Stay	4 days Interval 1.0 to 17.0	6 days Interval 2.0 to 22.0

Adverse Events

Budesonide and Formoterol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Budesonide and Formoterol n=29 participants at risk Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.	Placebo n=30 participants at risk Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Cardiac disorders Atrial flutter	0.00% 0/29 • 28 days	3.3% 1/30 • Number of events 1 • 28 days

Additional Information

Dr. Emir Festic

Mayo Clinic

Phone: 904-953-9758

Email: Festic.Emir@mayo.edu

Results disclosure agreements

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