suPAR-guided Anakinra Treatment for Validation of the Risk and Management of Respiratory Failure by COVID-19 (SAVE)

NCT04357366 | Completed Phase 2

• 2 other identifiers: SAVE2020-001466-11
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 28

Brief Summary

In the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure.

Conditions

COVID-19; Virus Diseases; Corona Virus Infection; Lower Respiratory Tract Infection Viral

Keywords

COVID-19; SARS-CoV-2; Anakinra; suPAR

Outcome Measures

Primary Outcomes (1)

• The ratio of patients who will develop serious respiratory failure (SRF)

  The primary study endpoint is the ratio of patients who will develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered achieving the primary endpoint.

  Visit study day 14

Secondary Outcomes (15)

• Comparison of the rate of patients who will develop serious respiratory failure (SRF) until day 14 with comparators from Hellenic Sepsis Study Group Database receiving standard-of-care treatment

  Visit study day 14

• Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7

  Visit study day 1, visit study day 7

• Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14

  Visit study day 1, visit study day 14

• Change of SOFA score in enrolled subjects between days 1 and 7

  Visit study day 1, visit study day 7

• Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14

  Visit study day 1, visit study day 14

Study Arms (1)

Anakinra

EXPERIMENTAL

Patients will receive 100mg of anakinra subcutaneously once daily for ten days. The drugs should be administered on the same time ± 2 hours every day. All other administered drugs are allowed. In case the patient is discharged home before the completion of 10 days of treatment, it is at the discretion of the investigator to suggest treatment continuation at home. In case such a decision is taken, the patient will be provided the required number of pre-filled syringes for daily self-injection. In this case, the patient should return the empty used syringes within 30 days.

Drug: Anakinra

Interventions

Anakinra DRUG

Treatment with 100mg Anakinra subcutaneously (sc) once daily for ten days

Also known as: Kineret

Anakinra

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal to or above 18 years
• Male or female gender
• In case of women, unwillingness to remain pregnant during the study period.
• Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent
• Confirmed infection by SARS-CoV-2 virus using molecular techniques as defined by the World Health Organization
• Findings in chest-X-ray or in chest computed tomography compatible with lower respiratory tract infection
• Plasma suPAR ≥6ng/ml

You may not qualify if:

• Age below 18 years
• Denial for written informed consent
• Any stage IV malignancy
• Any do not resuscitate decision
• Any primary immunodeficiency
• Less than 1,500 neutrophils/mm3
• Known hypersensitivity to anakinra
• Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg prednisone for a greater period than the last 15 days.
• Any anti-cytokine biological treatment the last one month
• Severe hepatic failure
• Severe renal failure
• Any need for CPAP or mechanical ventilation
• Any pO2/FiO2 ratio less than 150

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (28)

COVID-19 Department, General Hospital of Attica SISMANOGLEIO-AMALIA FLEMING

Marousi, Athens, 15126, Greece

Location

2nd Department of Internal Medicine, University General Hospital of Alexandroupolis

Alexandroupoli, 68100, Greece

Location

Department of Internal Medicine, I PAMMAKARISTOS Hospital

Athens, 11144, Greece

Location

1st Department of InternalMedicine, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S.

Athens, 11526, Greece

Location

1st Department of Internal Medicine, General Hospital of Athens G. GENNIMATAS

Athens, 11527, Greece

Location

1st University Department of Internal Medicine, General Hospital of Athens LAIKO

Athens, 11527, Greece

Location

1st University Departmentof Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseasesof Athens

Athens, 11527, Greece

Location

2nd University Department of Internal Medicine, IPPOKRATEION General Hospital of Athens

Athens, 11527, Greece

Location

3rd University Department of Internal Medicine, General Hospital of Chest Diseases of Athens I SOTIRIA

Athens, 11527, Greece

Location

Department of Internal Medicine, General Hospital of Chest Diseases of Athens I SOTIRIA

Athens, 11527, Greece

Location

Department of Clinical Therapeutics, ALEXANDRA General Hospital of Athens

Athens, 11528, Greece

Location

1st Department of Internal Medicine Amalia Fleming General Hospital

Athens, Greece

Location

1st Department of Internal Medicine, General Hospital of Eleusis THRIASIO

Athens, Greece

Location

1st Department of Internal Medicine, General Hospital of Nea Ionia CONSTANTOPOULIO-PATISION

Athens, Greece

Location

1st Department of Internal Medicine, General Hospital of Voula ASKLEPIEIO

Athens, Greece

Location

2nd Department of Internal Medicine, 251 Air Force General Hospital

Athens, Greece

Location

2nd Department of Internal Medicine, General Hospital of Eleusis THRIASIO

Athens, Greece

Location

3rd Department of Internal Medicine, General Hospital of Athens KORGIALENEIO-BENAKEIO E.E.S.

Athens, Greece

Location

5th Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece

Location

Department of Internal Medicine, General Hospital of Athens ELPIS

Athens, Greece

Location

Department of Infectious Diseases, General Hospital of Kerkira

Corfu, 49100, Greece

Location

1st Department of Internal Medicine, General University Hospital of Ioannina

Ioannina, 45500, Greece

Location

Department of Internal Medicine, General Hospital of Katerini

Katerini, 60100, Greece

Location

Department of Internal Medicine, University General Hospital of Larissa

Larissa, 41334, Greece

Location

Department of Internal Medicine, General Hospital of Larisa KOUTLIMBANEIO & ΤΡΙΑΝΤΑFΥLLΕΙΟ

Larissa, Greece

Location

Department of Internal Medicine, University General Hospital of Patras PANAGIA I VOITHIA

Pátrai, 26504, Greece

Location

2nd Department of Internal Medicine, General Hospital of Piraeus TZANEIO

Piraeus, Greece

Location

1st Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki

Thessaloniki, 54621, Greece

Location

Related Publications (6)

• Kyriazopoulou E, Akinosoglou K, Florou E, Kouriannidi E, Bogosian A, Tsachouridou O, Syrigos KN, Gatselis N, Milionis H, Papanikolaou IC, Sympardi S, Dafni M, Alevizou A, Amvrazi AV, Alexandrou E, Archontoulis K, Argyraki K, Alexiou Z, Georgiou Y, Gkogka D, Kyrailidi F, Kalyva V, Nikolopoulou T, Ioannou S, Bakakos P, Karathanassiou G, Koklanos K, Miletis DN, Tili AM, Vakkas L, Vila I, Panagopoulos P, Samarkos M, Chrysos G, Dalekos GN, Poulakou G, Metallidis S, Giamarellos-Bourboulis EJ. Anakinra efficacy in COVID-19 pneumonia guided by soluble urokinase plasminogen activator receptor: Association with the inflammatory burden of the host. Int J Antimicrob Agents. 2025 Jan;65(1):107405. doi: 10.1016/j.ijantimicag.2024.107405. Epub 2024 Dec 6.

  PMID: 39647797 DERIVED

• Kyriazopoulou E, Dalekos GN, Metallidis S, Poulakou G, Papanikolaou IC, Tzavara V, Argyraki K, Alexiou Z, Panagopoulos P, Samarkos M, Chrysos G, Tseliou A, Milionis H, Sympardi S, Vasishta A, Giamarellos-Bourboulis EJ. HEPARIN-BINDING PROTEIN LEVELS PREDICT UNFAVORABLE OUTCOME IN COVID-19 PNEUMONIA: A POST HOC ANALYSIS OF THE SAVE TRIAL. Shock. 2024 Mar 1;61(3):395-399. doi: 10.1097/SHK.0000000000002315. Epub 2024 Jan 19.

  PMID: 38517242 DERIVED

• Keur N, Saridaki M, Ricano-Ponce I, Netea MG, Giamarellos-Bourboulis EJ, Kumar V. Analysis of inflammatory protein profiles in the circulation of COVID-19 patients identifies patients with severe disease phenotypes. Respir Med. 2023 Oct;217:107331. doi: 10.1016/j.rmed.2023.107331. Epub 2023 Jun 25.

  PMID: 37364721 DERIVED

• Samaras C, Kyriazopoulou E, Poulakou G, Reiner E, Kosmidou M, Karanika I, Petrakis V, Adamis G, Gatselis NK, Fragkou A, Rapti A, Taddei E, Kalomenidis I, Chrysos G, Bertoli G, Kainis I, Alexiou Z, Castelli F, Saverio Serino F, Bakakos P, Nicastri E, Tzavara V, Kostis E, Dagna L, Koukidou S, Tzatzagou G, Chini M, Bassetti M, Trakatelli C, Tsoukalas G, Selmi C, Samarkos M, Pyrpasopoulou A, Masgala A, Antonakis E, Argyraki A, Akinosoglou K, Sympardi S, Panagopoulos P, Milionis H, Metallidis S, Syrigos KN, Angel A, Dalekos GN, Netea MG, Giamarellos-Bourboulis EJ. Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia. Cytokine. 2023 Feb;162:156111. doi: 10.1016/j.cyto.2022.156111. Epub 2022 Dec 14.

  PMID: 36529030 DERIVED

• Renieris G, Karakike E, Gkavogianni T, Droggiti DE, Stylianakis E, Andriopoulou T, Spanou VM, Kafousopoulos D, Netea MG, Eugen-Olsen J, Simard J, Giamarellos-Bourboulis EJ. IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19. J Innate Immun. 2022;14(6):643-656. doi: 10.1159/000524560. Epub 2022 May 11.

  PMID: 35545011 DERIVED

• Kyriazopoulou E, Panagopoulos P, Metallidis S, Dalekos GN, Poulakou G, Gatselis N, Karakike E, Saridaki M, Loli G, Stefos A, Prasianaki D, Georgiadou S, Tsachouridou O, Petrakis V, Tsiakos K, Kosmidou M, Lygoura V, Dareioti M, Milionis H, Papanikolaou IC, Akinosoglou K, Myrodia DM, Gravvani A, Stamou A, Gkavogianni T, Katrini K, Marantos T, Trontzas IP, Syrigos K, Chatzis L, Chatzis S, Vechlidis N, Avgoustou C, Chalvatzis S, Kyprianou M, van der Meer JW, Eugen-Olsen J, Netea MG, Giamarellos-Bourboulis EJ. An open label trial of anakinra to prevent respiratory failure in COVID-19. Elife. 2021 Mar 8;10:e66125. doi: 10.7554/eLife.66125.

  PMID: 33682678 DERIVED

MeSH Terms

Conditions

COVID-19; Virus Diseases; Coronavirus Infections

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Simeon Metallidis, MD, PhD

  Aristotle University of Thessaloniki, Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment with anakinra

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 22, 2020
• Study Start: April 15, 2020
• Primary Completion: January 29, 2022
• Study Completion: April 15, 2022
• Last Updated: July 13, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GR (28)