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

Covid19 Clinical Trial

— DAMPENCOVID  

Official title:

Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04445285
• Other study ID #: USAH 1002 000
• Status: Recruiting
• Phase: Phase 2
• Start date: April 28, 2020
• Est. completion date: February 28, 2022

Study information

• Verified date: May 2021
• Source: University of South Alabama
• Contact: Jon D Simmons, M.D.
• Phone: 12514459834
• Email: jdsimmons[@]health.southalabama.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: February 28, 2022
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Covid19
• Respiratory Insufficiency

Intervention

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

Locations

Country	Name	City	State
United States	University of South Alabama	Mobile	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
Jon Simmons	University of South Alabama

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality at 28 days	All Cause Mortality at 28 days	28 days after enrollment
Primary	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	Respiratory Response	Proportion of patients alive and free of invasive mechanical ventilation at 28 days invasive mechanical ventilation at 28 days	28 days
Secondary	Legnth of ICU Stay	Proportion of patients alive and discharged from the ICU at 28 days discharged from the ICU at 28 days	28 days
Secondary	Legnth of Hospital Stay	Proportion of patients alive and discharged from the hospital at 28 days	28 days
Secondary	Respiratory Response	Alive, respiratory failure-free days at 28 days	28 days
Secondary	Pulmonary Function	Pulmonary Function Ratio at 5 days	5 days