A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19

NCT ID: NCT04362059

Last Updated: 2023-09-29

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

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-18

Study Completion Date

2023-01-30

Brief Summary

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Lung surfactant is present in the lungs. It covers the alveolar surface where it reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. This study will introduce surfactant to the patients lungs via the COVSurf Drug Delivery System

Detailed Description

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The hypothesis behind the proposed trial of surfactant therapy for COVID-19 infected patients requiring ventilator support is that endogenous surfactant is dysfunctional. This could be due to decreased concentration of surfactant phospholipid and protein, altered surfactant phospholipid composition, surfactant protein proteolysis and/or oedema protein inhibition of surfactant surface tension function and/or oxidative inactivation of surfactant proteins. Variations of these dysfunctional mechanisms have been reported in a range of lung diseases, including cystic fibrosis and severe asthma, and in child and adult patients with ARDS. Our studies of surfactant metabolism in adult ARDS patients showed altered percentage composition of surfactant PC, with decreased DPPC and increased surface tension-inactive unsaturated species, and decreased concentrations of both total PC and phosphatidylglycerol (PG)

The SARS-CoV-2 virus binds to the angiotensin converting enzyme-2 (ACE2) receptor, which is preferentially expressed in the peripheral lung ATII cells. Consequent viral infection of ATII cells could reduce cell number and impair the capacity of the lungs to synthesise and secrete surfactant. This, however, has not yet been demonstrated empirically in COVID-19 patients. If this is the case, then exogenous surfactant administration to the lungs is potential one treatment option to mitigate disease severity in these patients.

Conditions

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Respiratory Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment Arm

Patients will be administered surfactant via COVSurf Drug Delivery System

Group Type EXPERIMENTAL

COVSurf Drug Delivery System

Intervention Type DEVICE

Device introduces surfactant to the patients lungs

Control Arm

Patients shall receive regular Standard of Care treatment

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type OTHER

Standard of care treatment for respiratory illness

Interventions

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COVSurf Drug Delivery System

Device introduces surfactant to the patients lungs

Intervention Type DEVICE

Standard of Care

Standard of care treatment for respiratory illness

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years old
* Confirmed COVID-19 positive by PCR
* Within 24 hours of mechanical ventilation (ETI arm) or within 24 hours of needing either CPAP or NIV (CPAP/NIV arm)
* Assent or professional assent obtained

Exclusion Criteria

* Imminent expected death within 24 hours
* Specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary haemorrhage)
* Known or suspected pregnancy
* Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR \< 30)
* Liver failure
* Anticipated transfer to another hospital, which is not a study site within 72 hours.
* Current participation or participation in another study within the last month that in the opinion of the investigator would prevent enrollment for safety purposes.
* Consent Declined
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael P Grocott, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Southampton NHS Foundation Trust

Locations

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University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Anzueto A, Baughman RP, Guntupalli KK, Weg JG, Wiedemann HP, Raventos AA, Lemaire F, Long W, Zaccardelli DS, Pattishall EN. Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med. 1996 May 30;334(22):1417-21. doi: 10.1056/NEJM199605303342201.

Reference Type RESULT
PMID: 8618579 (View on PubMed)

Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial. Collaborative European Multicenter Study Group. Pediatrics. 1988 Nov;82(5):683-91.

Reference Type RESULT
PMID: 2903480 (View on PubMed)

Dushianthan A, Goss V, Cusack R, Grocott MP, Postle AD. Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome. Respir Res. 2014 Nov 7;15(1):128. doi: 10.1186/s12931-014-0128-8.

Reference Type RESULT
PMID: 25378080 (View on PubMed)

Goss V, Hunt AN, Postle AD. Regulation of lung surfactant phospholipid synthesis and metabolism. Biochim Biophys Acta. 2013 Feb;1831(2):448-58. doi: 10.1016/j.bbalip.2012.11.009. Epub 2012 Nov 27.

Reference Type RESULT
PMID: 23200861 (View on PubMed)

Gunther A, Schmidt R, Harodt J, Schmehl T, Walmrath D, Ruppert C, Grimminger F, Seeger W. Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on biophysical and biochemical surfactant properties. Eur Respir J. 2002 May;19(5):797-804. doi: 10.1183/09031936.02.00243302.

Reference Type RESULT
PMID: 12030716 (View on PubMed)

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.

Reference Type RESULT
PMID: 32142651 (View on PubMed)

Moller JC, Schaible T, Roll C, Schiffmann JH, Bindl L, Schrod L, Reiss I, Kohl M, Demirakca S, Hentschel R, Paul T, Vierzig A, Groneck P, von Seefeld H, Schumacher H, Gortner L; Surfactant ARDS Study Group. Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study. Intensive Care Med. 2003 Mar;29(3):437-46. doi: 10.1007/s00134-003-1650-1. Epub 2003 Feb 15.

Reference Type RESULT
PMID: 12589529 (View on PubMed)

Postle AD, Mander A, Reid KB, Wang JY, Wright SM, Moustaki M, Warner JO. Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. Am J Respir Cell Mol Biol. 1999 Jan;20(1):90-8. doi: 10.1165/ajrcmb.20.1.3253.

Reference Type RESULT
PMID: 9870921 (View on PubMed)

Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020 May 21;526(1):135-140. doi: 10.1016/j.bbrc.2020.03.044. Epub 2020 Mar 19.

Reference Type RESULT
PMID: 32199615 (View on PubMed)

Rebello CM, Jobe AH, Eisele JW, Ikegami M. Alveolar and tissue surfactant pool sizes in humans. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):625-8. doi: 10.1164/ajrccm.154.3.8810596.

Reference Type RESULT
PMID: 8810596 (View on PubMed)

Rodriguez-Capote K, Manzanares D, Haines T, Possmayer F. Reactive oxygen species inactivation of surfactant involves structural and functional alterations to surfactant proteins SP-B and SP-C. Biophys J. 2006 Apr 15;90(8):2808-21. doi: 10.1529/biophysj.105.073106. Epub 2006 Jan 27.

Reference Type RESULT
PMID: 16443649 (View on PubMed)

Schmidt R, Markart P, Ruppert C, Wygrecka M, Kuchenbuch T, Walmrath D, Seeger W, Guenther A. Time-dependent changes in pulmonary surfactant function and composition in acute respiratory distress syndrome due to pneumonia or aspiration. Respir Res. 2007 Jul 27;8(1):55. doi: 10.1186/1465-9921-8-55.

Reference Type RESULT
PMID: 17662121 (View on PubMed)

Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med. 1996;21(5):641-9. doi: 10.1016/0891-5849(96)00131-1.

Reference Type RESULT
PMID: 8891667 (View on PubMed)

Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016/S1473-3099(20)30086-4. Epub 2020 Feb 24.

Reference Type RESULT
PMID: 32105637 (View on PubMed)

Dushianthan A, Clark H, Madsen J, Mogg R, Matthews L, Berry L, de la Serna JB, Batchelor J, Brealey D, Hussell T, Porter J, Djukanovic R, Feelisch M, Postle A, Grocott MPW. Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Dec 10;21(1):1014. doi: 10.1186/s13063-020-04944-5.

Reference Type DERIVED
PMID: 33302976 (View on PubMed)

Related Links

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Other Identifiers

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RHM CRI0399

Identifier Type: -

Identifier Source: org_study_id

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