NCT04445285

Brief Summary

This Phase 2 Randomized Placebo Controlled Trial will determine if administering nebulized Dornase Alpha (rhDNase) to COVID-19 patients with respiratory failure is safe and will reduce 28-day mortality.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
44

participants targeted

Target at P25-P50 for phase_2 covid19

Timeline
Completed

Started Apr 2020

Longer than P75 for phase_2 covid19

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 28, 2020

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

June 22, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 24, 2020

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2021

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2022

Completed
Last Updated

May 28, 2021

Status Verified

May 1, 2021

Enrollment Period

1.6 years

First QC Date

June 22, 2020

Last Update Submit

May 26, 2021

Conditions

Covid19

Keywords

Covid-19, Coronavirus

Outcome Measures

Primary Outcomes (2)

  • Mortality at 28 days

    All Cause Mortality at 28 days

    28 days after enrollment

  • Systemic Therapeutic Response

    To assess the effect of Pulmozyme® on the severity of respiratory failure, systemic inflammatory response, and multi-organ failure.

    5 days after enrollment

Secondary Outcomes (5)

  • Respiratory Response

    28 days

  • Legnth of ICU Stay

    28 days

  • Legnth of Hospital Stay

    28 days

  • Respiratory Response

    28 days

  • Pulmonary Function

    5 days

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Patient will receive 2.5mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses.

Drug: Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase)

Placebo Arm 0.9% sodium chloride

PLACEBO COMPARATOR

Patient will receive 2.5ml of Sodium Chloride 0.9% aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses.

Drug: 0.9%sodium chloride

Interventions

Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase)DRUG

2.5mg Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) aerosolized treatment once every 24 hours for five (5) consecutive days; a total of five (5) doses

Treatment Arm
0.9%sodium chlorideDRUG

Placebo of 0.9% sodium chloride every 24 hours for five (5) consecutive days; a total of 5 doses

Placebo Arm 0.9% sodium chloride

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or Female age 18 or older
  • On high flow oxygen =/\> 6 liters nasal cannula (or)
  • On mechanical ventilation
  • Clinical diagnosis of COVID-19 \& positive PCR test (or)
  • Clinical diagnosis of COVID-19 \& negative PCR test with clinical symptoms of COVID-19 and pathognomonic lesions on a chest CT scan

You may not qualify if:

  • Known allergy to Pulmozyme
  • Less than 18 years of age
  • Grave condition with anticipated death within 48 hours; at the discretion of treating physician.
  • Enrollment in another clinical trial receiving investigatory drugs

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of South Alabama

Mobile, Alabama, 36617, United States

RECRUITING

Related Publications (11)

  • Simmons JD, Lee YL, Mulekar S, Kuck JL, Brevard SB, Gonzalez RP, Gillespie MN, Richards WO. Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects. Ann Surg. 2013 Oct;258(4):591-6; discussion 596-8. doi: 10.1097/SLA.0b013e3182a4ea46.

    PMID: 23979273BACKGROUND

  • Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):104-7. doi: 10.1038/nature08780.

    PMID: 20203610BACKGROUND

  • Schumacker PT, Gillespie MN, Nakahira K, Choi AM, Crouser ED, Piantadosi CA, Bhattacharya J. Mitochondria in lung biology and pathology: more than just a powerhouse. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L962-74. doi: 10.1152/ajplung.00073.2014. Epub 2014 Apr 18.

    PMID: 24748601BACKGROUND

  • Kuck JL, Obiako BO, Gorodnya OM, Pastukh VM, Kua J, Simmons JD, Gillespie MN. Mitochondrial DNA damage-associated molecular patterns mediate a feed-forward cycle of bacteria-induced vascular injury in perfused rat lungs. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1078-85. doi: 10.1152/ajplung.00015.2015. Epub 2015 Mar 20.

    PMID: 25795724BACKGROUND

  • Dobson AW, Grishko V, LeDoux SP, Kelley MR, Wilson GL, Gillespie MN. Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L205-10. doi: 10.1152/ajplung.00443.2001.

    PMID: 12060578BACKGROUND

  • Ruchko MV, Gorodnya OM, Zuleta A, Pastukh VM, Gillespie MN. The DNA glycosylase Ogg1 defends against oxidant-induced mtDNA damage and apoptosis in pulmonary artery endothelial cells. Free Radic Biol Med. 2011 May 1;50(9):1107-13. doi: 10.1016/j.freeradbiomed.2010.10.692. Epub 2010 Oct 20.

    PMID: 20969951BACKGROUND

  • Chouteau JM, Obiako B, Gorodnya OM, Pastukh VM, Ruchko MV, Wright AJ, Wilson GL, Gillespie MN. Mitochondrial DNA integrity may be a determinant of endothelial barrier properties in oxidant-challenged rat lungs. Am J Physiol Lung Cell Mol Physiol. 2011 Dec;301(6):L892-8. doi: 10.1152/ajplung.00210.2011. Epub 2011 Sep 2.

    PMID: 21890512BACKGROUND

  • Gebb SA, Decoux A, Waggoner A, Wilson GL, Gillespie MN. Mitochondrial DNA damage mediates hyperoxic dysmorphogenesis in rat fetal lung explants. Neonatology. 2013;103(2):91-7. doi: 10.1159/000342632. Epub 2012 Nov 15.

    PMID: 23154780BACKGROUND

  • Hashizume M, Mouner M, Chouteau JM, Gorodnya OM, Ruchko MV, Potter BJ, Wilson GL, Gillespie MN, Parker JC. Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice. Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L287-97. doi: 10.1152/ajplung.00071.2012. Epub 2012 Dec 14.

    PMID: 23241530BACKGROUND

  • Simmons JD, Freno DR, Muscat CA, Obiako B, Lee YL, Pastukh VM, Brevard SB, Gillespie MN. Mitochondrial DNA damage associated molecular patterns in ventilator-associated pneumonia: Prevention and reversal by intratracheal DNase I. J Trauma Acute Care Surg. 2017 Jan;82(1):120-125. doi: 10.1097/TA.0000000000001269.

    PMID: 27787436BACKGROUND

  • Grishko V, Solomon M, Wilson GL, LeDoux SP, Gillespie MN. Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1300-8. doi: 10.1152/ajplung.2001.280.6.L1300.

    PMID: 11350811BACKGROUND

MeSH Terms

Conditions

COVID-19Coronavirus Infections

Interventions

dornase alfaSodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Central Study Contacts

Jon D Simmons, M.D.

CONTACT

12514459834jdsimmons@health.southalabama.edu

Wendy Blount, RN, MSN

CONTACT

2514554566wlblount@health.southalabama.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Chief, Division of Trauma & Acute Care Surgery

Study Record Dates

First Submitted

June 22, 2020

First Posted

June 24, 2020

Study Start

April 28, 2020

Primary Completion

November 30, 2021

Study Completion

February 28, 2022

Last Updated

May 28, 2021

Record last verified: 2021-05

Locations

US(1)