NCT04362059

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

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

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jun 2020

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

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

First Submitted

Initial submission to the registry

April 20, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 24, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

June 18, 2020

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2023

Completed
Last Updated

September 29, 2023

Status Verified

September 1, 2023

Enrollment Period

2.5 years

First QC Date

April 20, 2020

Last Update Submit

September 26, 2023

Conditions

Respiratory Infections

Outcome Measures

Primary Outcomes (3)

  • Oxygenation Improvement

    To assess the improvement in oxygenation as determined by the PaO2/FiO2 ratio after treatment with study treatment

    3 months

  • Pulmonary ventilation Improvement

    To assess the improvement in pulmonary ventilation as determined by the Ventilation Index (VI), where VI = (Respiratory rate X PIP X PaCo2 (mmHg)/ 1000 after study treatment.

    3 months

  • IMV Need

    Need for invasive mechanical ventilation (IMV) (CPAP/NIV arm only)

    3 months

Secondary Outcomes (13)

  • Safety Assessment of Frequency and Severity of Adverse Events

    3 months

  • Change in PaO2/FiO2 ratio

    3 months

  • Mean Change in ventilatory index

    48 hours

  • Mean Change in pulmonary compliance

    48 hours

  • Mean Change in PEEP requirement

    48 Hours

  • +8 more secondary outcomes

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Patients will be administered surfactant via COVSurf Drug Delivery System

Device: COVSurf Drug Delivery System

Control Arm

ACTIVE COMPARATOR

Patients shall receive regular Standard of Care treatment

Other: Standard of Care

Interventions

COVSurf Drug Delivery SystemDEVICE

Device introduces surfactant to the patients lungs

Treatment Arm
Standard of CareOTHER

Standard of care treatment for respiratory illness

Control Arm

Eligibility Criteria

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

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Related Publications (15)

  • 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.

    PMID: 8618579RESULT

  • 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.

    PMID: 2903480RESULT

  • 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.

    PMID: 25378080RESULT

  • 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.

    PMID: 23200861RESULT

  • 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.

    PMID: 12030716RESULT

  • 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.

    PMID: 32142651RESULT

  • 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.

    PMID: 12589529RESULT

  • 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.

    PMID: 9870921RESULT

  • 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.

    PMID: 32199615RESULT

  • 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.

    PMID: 8810596RESULT

  • 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.

    PMID: 16443649RESULT

  • 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.

    PMID: 17662121RESULT

  • 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.

    PMID: 8891667RESULT

  • 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.

    PMID: 32105637RESULT

  • 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.

    PMID: 33302976DERIVED

Related Links

MeSH Terms

Conditions

Respiratory Tract Infections

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

InfectionsRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Michael P Grocott, MD

    University Hospital Southampton NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 20, 2020

First Posted

April 24, 2020

Study Start

June 18, 2020

Primary Completion

November 30, 2022

Study Completion

January 30, 2023

Last Updated

September 29, 2023

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share

Locations

GB(2)