Trial Outcomes & Findings for Dornase Alfa for ARDS in Patients With Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) (NCT NCT04402970)

NCT ID: NCT04402970

Last Updated: 2021-04-14

Results Overview

Daily evaluation of PaO2/FiO2 ratio at baseline prior to starting therapy and on days 1,2,3,4,5 and 14 if applicable

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 30 participants
• Primary outcome timeframe: 14 days
• Results posted on: 2021-04-14

Participant Flow

Non-randomized 10 patients in inhaled dornase alfa arm and 20 patients in case-control (standard of care) arm

Participant milestones

Measure	Inhaled/Nebulized Dornase Alfa Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care Standard of care provided for Acute Respiratory Distress Syndrome (ARDS)
Overall Study STARTED	10	20
Overall Study COMPLETED	10	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dornase Alfa for ARDS in Patients With Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)

Baseline characteristics by cohort

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.	Total n=30 Participants Total of all reporting groups
Age, Continuous	62 years n=93 Participants	58 years n=4 Participants	60 years n=27 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	7 Participants n=4 Participants	11 Participants n=27 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	13 Participants n=4 Participants	19 Participants n=27 Participants
Race/Ethnicity, Customized White, non-Hispanic	8 Participants n=93 Participants	16 Participants n=4 Participants	24 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Region of Enrollment United States	10 participants n=93 Participants	20 participants n=4 Participants	30 participants n=27 Participants
Diabetes mellitus	7 Participants n=93 Participants	11 Participants n=4 Participants	18 Participants n=27 Participants
Hypertension	9 Participants n=93 Participants	14 Participants n=4 Participants	23 Participants n=27 Participants
Coronary artery disease	5 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants
Chronic lung disease (COPD, asthma, ILD)	3 Participants n=93 Participants	7 Participants n=4 Participants	10 Participants n=27 Participants
Obesity	8 Participants n=93 Participants	17 Participants n=4 Participants	25 Participants n=27 Participants
Remdesivir	9 Participants n=93 Participants	20 Participants n=4 Participants	29 Participants n=27 Participants
Corticosteroids	9 Participants n=93 Participants	20 Participants n=4 Participants	29 Participants n=27 Participants
Antibiotics	10 Participants n=93 Participants	19 Participants n=4 Participants	29 Participants n=27 Participants
Convalescent Plasma	9 Participants n=93 Participants	11 Participants n=4 Participants	20 Participants n=27 Participants
Anticoagulation	4 Participants n=93 Participants	10 Participants n=4 Participants	14 Participants n=27 Participants
Paralytics	8 Participants n=93 Participants	19 Participants n=4 Participants	27 Participants n=27 Participants
Prone positioning	8 Participants n=93 Participants	16 Participants n=4 Participants	24 Participants n=27 Participants

PRIMARY outcome

Timeframe: 14 days

Population: Number of patients still on mechanical ventilation and who underwent arterial blood gas monitoring to determine PaO2/FiO2 ratio

Daily evaluation of PaO2/FiO2 ratio at baseline prior to starting therapy and on days 1,2,3,4,5 and 14 if applicable

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Day 14	55 mmHg Interval -150.8 to 260.8	-11.2 mmHg Interval -92.6 to 70.2
Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Day 1	10.7 mmHg Interval -29.7 to 51.1	21.4 mmHg Interval -0.8 to 43.6
Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Day 2	61.1 mmHg Interval 5.2 to 117.0	11.8 mmHg Interval -9.6 to 33.1
Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Day 3	23.5 mmHg Interval -21.0 to 68.0	12.5 mmHg Interval -9.7 to 34.7
Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Day 4	24.1 mmHg Interval -21.8 to 70.1	3.5 mmHg Interval -24.8 to 31.7
Change in Arterial Blood Oxygen Content to Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Day 5	37.6 mmHg Interval -35.9 to 111.0	5 mmHg Interval -28.8 to 38.8

SECONDARY outcome

Timeframe: 14 days

Population: Patients on mechanical ventilation with acute respiratory distress syndrome secondary to COVID-19

Daily evaluation of static lung compliance, measured by change in driving pressure over volume delivered, at baseline prior to starting therapy and on days 1,2,3,4,5 and 14 if applicable

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Change in Static Lung Compliance Day 1	3.1 mL/cmH20 Interval -1.7 to 7.9	-0.1 mL/cmH20 Interval -4.2 to 3.9
Change in Static Lung Compliance Day 2	4 mL/cmH20 Interval -1.0 to 9.0	-0.4 mL/cmH20 Interval -3.1 to 2.3
Change in Static Lung Compliance Day 3	6.3 mL/cmH20 Interval -0.8 to 13.3	-5.7 mL/cmH20 Interval -9.8 to -1.6
Change in Static Lung Compliance Day 4	4 mL/cmH20 Interval -3.2 to 11.3	-5.6 mL/cmH20 Interval -9.4 to -1.8
Change in Static Lung Compliance Day 5	7.4 mL/cmH20 Interval -1.8 to 16.6	-4.8 mL/cmH20 Interval -8.4 to -1.3
Change in Static Lung Compliance Day 14	0.8 mL/cmH20 Interval -16.3 to 17.8	-10.2 mL/cmH20 Interval -17.9 to -2.4

SECONDARY outcome

Timeframe: From start of mechanical ventilation until extubation or date of death from any cause, whichever came first, assessed up to 6 months

Number of days on mechanical ventilation

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Duration of Mechanical Ventilation	15.2 Days Interval 5.0 to 29.0	18.2 Days Interval 8.0 to 38.0

SECONDARY outcome

Timeframe: From date of first admission to intensive care unit until discharge/transfer out of the ICU or date of death from any cause, whichever came first, assessed up to 6 months

Number of days in the medical intensive care unit

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Length of ICU Stay	16.5 Days Interval 7.0 to 30.0	22.1 Days Interval 11.0 to 47.0

SECONDARY outcome

Timeframe: From date of hospital admission until discharge from acute care hospital or date of death from any cause, whichever came first, assessed up to 6 months

Number of days as an inpatient at the University of Missouri

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Length of Hospitalization	22.5 Days Interval 8.0 to 52.0	28.7 Days Interval 15.0 to 60.0

SECONDARY outcome

Timeframe: From date of randomization until first positive culture or clinical diagnosis of infection if occurs, assessed up to 3 months

Determination of secondary bacterial infections based upon positive culture results and clinical diagnosis by treating physician.

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Secondary Bacterial Infections	30 Percentage of participants Interval -5.0 to 65.0	25 Percentage of participants Interval 4.0 to 46.0

SECONDARY outcome

Timeframe: 28 and 90 day evaluation

All cause mortality

Outcome measures

Measure	Inhaled/Nebulized Dornase Alfa n=10 Participants Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 Participants Standard of care provided for ARDS.
Mortality 28 days	40 Percentage of participants Interval 4.0 to 77.0	45 Percentage of participants Interval 21.0 to 69.0
Mortality 90 days	40 Percentage of participants Interval 4.0 to 77.0	55 Percentage of participants Interval 31.0 to 79.0

Adverse Events

Inhaled/Nebulized Dornase Alfa

Serious events: 4 serious events

Other events: 0 other events

Deaths: 4 deaths

Standard of Care

Serious events: 10 serious events

Other events: 0 other events

Deaths: 11 deaths

Serious adverse events

Measure	Inhaled/Nebulized Dornase Alfa n=10 participants at risk Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 participants at risk Standard of care provided for ARDS.
Infections and infestations Bacteremia	10.0% 1/10 • Number of events 1 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.	15.0% 3/20 • Number of events 3 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.
Infections and infestations Ventilator associated pneumonia	30.0% 3/10 • Number of events 3 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.	25.0% 5/20 • Number of events 5 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.
Respiratory, thoracic and mediastinal disorders Venovenous extracorporeal membrane oxygenation	0.00% 0/10 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.	10.0% 2/20 • Number of events 2 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.

Other adverse events

Measure	Inhaled/Nebulized Dornase Alfa n=10 participants at risk Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. Dornase Alfa Inhalation Solution: Nebulized dornase alfa	Standard of Care n=20 participants at risk Standard of care provided for ARDS.
Respiratory, thoracic and mediastinal disorders Allergic reaction to drug	0.00% 0/10 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.	0.00% 0/20 • Adverse event data was collected until end of hospitalization, death or up to 120 days whichever came first. Secondary pulmonary infections after the start of mechanical ventilation was the main adverse event data collected. Additional adverse events collected included development of blood stream infections or escalation of oxygenation support by need of extracorporeal membrane oxygenation therapy.

Additional Information

Dr. Zach Holliday

University of Missouri

Phone: 5738829072

Email: hollidayz@health.missouri.edu

Results disclosure agreements

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