Phase 2 Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure

NCT ID: NCT04445285

Last Updated: 2021-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-28

Study Completion Date

2022-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Covid19

Keywords

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Covid-19, Coronavirus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Treatment Arm

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.

Group Type EXPERIMENTAL

Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase)

Intervention Type 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

Placebo Arm 0.9% sodium chloride

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.

Group Type PLACEBO_COMPARATOR

0.9%sodium chloride

Intervention Type DRUG

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

Interventions

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Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase)

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

Intervention Type DRUG

0.9%sodium chloride

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of South Alabama

OTHER

Sponsor Role collaborator

Jon Simmons

OTHER

Sponsor Role lead

Responsible Party

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Jon Simmons

Chief, Division of Trauma & Acute Care Surgery

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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University of South Alabama

Mobile, Alabama, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jon D Simmons, M.D.

Role: CONTACT

Phone: 12514459834

Email: [email protected]

Wendy Blount, RN, MSN

Role: CONTACT

Phone: 2514554566

Email: [email protected]

Facility Contacts

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Jon Simmons, M.D.

Role: primary

Wendy Blount, RN, MSN

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 23979273 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20203610 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24748601 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25795724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12060578 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20969951 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21890512 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23154780 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23241530 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27787436 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11350811 (View on PubMed)

Other Identifiers

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USAH 1002 000

Identifier Type: -

Identifier Source: org_study_id