Dornase Alfa Administered to Patients With COVID-19 (DACOVID) (DACOVID)

Nebulized In-line Endotracheal Dornase Alfa and Albuterol Administered to Mechanically Ventilated COVID-19 Patients: A Case Series

Mechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19-acting as a mucolytic and targeting NETs.

Study Overview

• Status: Completed
• Conditions: COVID-19; Mechanical Ventilation
• Intervention / Treatment: Drug: Dornase Alfa

Detailed Description

Demographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO)-treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • New York
    • Manhasset, New York, United States, 11030
      • Feinstein Insitute for Medical Research at Northwell Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

mechanically ventilated patients with COVID-19

Description

Inclusion Criteria:

• mechanically ventilated patients with COVID-19

Exclusion Criteria:

• healthy, non-ventilated

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants discharged from the intensive care unit (ICU)	discharge from ICU will be determined from the enterprise health record reporting database	2 months
Number of participants who survived COVID-19	survival will be determined from the enterprise health record reporting database	2-4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in FiO2	fraction of inspired oxygen requirements will be measured	2 months

Collaborators and Investigators

• Sponsor: Feinstein Institute for Medical Research
• Collaborators: Cold Spring Harbor Laboratory
• Investigators: Principal Investigator: Betsy J Barnes, Feinstein Institute for Medical Research

Publications and helpful links

General Publications

• Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, Dassler-Plenker J, Guerci P, Huynh C, Knight JS, Loda M, Looney MR, McAllister F, Rayes R, Renaud S, Rousseau S, Salvatore S, Schwartz RE, Spicer JD, Yost CC, Weber A, Zuo Y, Egeblad M. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020 Jun 1;217(6):e20200652. doi: 10.1084/jem.20200652.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2020
• Primary Completion (Actual): April 24, 2020
• Study Completion (Actual): September 4, 2020

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: 216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: study will be published and data will be made available
• IPD Sharing Time Frame: 3-6 months
• IPD Sharing Access Criteria: de-identified data
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No