suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19

NCT04680949 | Completed Phase 3 DMC

• 1 other identifier: SAVE-MORE
• Study Type: interventional
• Target: 606
• Locations: 2 countries
• Sites: 40

Brief Summary

The SAVE-MORE is a pivotal, confirmatory, phase III randomized clinical trial (RCT) aiming to evaluate the efficacy and safety of early start of anakinra guided by suPAR in patients with LRTI by SARS-CoV-2 in improving the clinical state of COVID-19 over 28 days as measured by the ordinal scale of the 11-point World Health Organization (WHO) clinical progression scale (CPS).

Conditions

Covid19

Keywords

SARS-CoV 2; anakinra

Outcome Measures

Primary Outcomes (1)

• Comparison of the distribution of frequencies of each score of a 5-scale patient state evaluated from the 11-point WHO Clinical Progression ordinal Scale (CPS) between the two arms of treatment

  Comparison of the distribution of frequencies of each score of the 5-scale patient state evaluated from the 11-point WHO Clinical Progression ordinal Scale (CPS) between the two arms of treatment by Day 28. This will be expressed as the distribution of the frequencies of each score of the scale in each arm of treatment by Day 28. The scale ranges from 0 (best outcome-asymptomatic) to 11 (worst outcome-death).

  28 days

Secondary Outcomes (22)

• Absolute change of the measure of the 11-point of WHO Clinical Progression ordinal Scale (CPS)

  28 days

• Relative change of the measure of the 11-point of WHO Clinical Progression ordinal Scale (CPS)

  28 days

• Absolute change of the measure of the 11-point of WHO Clinical Progression ordinal Scale (CPS)

  14 days

• Relative change of the measure of the 11-point of WHO Clinical Progression ordinal Scale (CPS)

  14 days

• Absolute change of the SOFA score

  14 days

Other Outcomes (3)

• Cost of hospitalization

  90 days

• Comparison of the distribution of frequencies of each score of a 5-scale patient state

  60 days

• Comparison of the distribution of frequencies of each score of a 5-scale patient state

  90 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients receiving standard-of-care (SOC) and placebo. Placebo is injected subcutaneously once daily for 10 days

Drug: Placebo

Anakinra

EXPERIMENTAL

Patients receiving SOC and anakinra. Anakinra is injected subcutaneously as 100 mg once daily for 10 days

Drug: Anakinra

Interventions

Anakinra DRUG

Standard-of-care and anakinra. Anakinra is injected subcutaneously as 100 mg once daily for 10 days

Also known as: Kineret

Anakinra

Placebo DRUG

Standard-of-care and placebo. Placebo is injected subcutaneously once daily for 10 days

Placebo

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. For subjects without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation in the Member State where the trial is planned.
• Confirmed infection by SARS-CoV-2 virus
• Findings in chest-X-ray or in chest computed tomography compatible with lower respiratory tract infection
• Need for hospitalization for COVID-19. The need for hospitalization is defined by the attending physician taking into consideration clinical presentation, requirement for supportive care, potential risk factors for severe disease, and conditions at home, including the presence of vulnerable persons in the household.
• 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
• Αny pO2/FiO2 (partial oxygen pressure to fraction of inspired oxygen) ratio less than 150 mmHg irrespective if the patient is under mechanical ventilation (MV) / non-invasive ventilation (NIV) / extracorporeal membrane oxygenation (ECMO) or not
• Patient under MV or NIV or ECMO
• Any primary immunodeficiency
• Less than 1,500 neutrophils/mm3
• Plasma suPAR less than 6 ng/ml
• Known hypersensitivity to anakinra
• Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg/kg prednisone for a period greater than the last 15 days.
• Any anti-cytokine biological treatment the last one month
• Severe hepatic failure defined as Child-Pugh stage of 3
• End-stage renal failure necessitating hemofiltration or peritoneal hemodialysis
• Participation in any other interventional trial

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (40)

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

Alexandroupoli, Greece

Location

10th Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece

Location

1st Department of Internal Medicine, AMALIA FLEMING Prefecture General Hospital of Melissia

Athens, Greece

Location

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

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

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

Athens, Greece

Location

1st University Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece

Location

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

Athens, Greece

Location

2nd Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece

Location

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

Athens, Greece

Location

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

Athens, Greece

Location

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

Athens, Greece

Location

4th Department of Internal Medicine, ATTIKON University General Hospital

Athens, Greece

Location

4th Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece

Location

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

Athens, Greece

Location

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

Athens, Greece

Location

Department of Clinical Therapeutics, ALEXANDRA General Hospital of Athens

Athens, Greece

Location

Department of COVID-19, Evangelismos General Hospital

Athens, Greece

Location

Department of Internal Medicine, General Hospital of Athens Elpis

Athens, Greece

Location

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

Athens, Greece

Location

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

Athens, Greece

Location

Department of Pulmonary Medicine, General Hospital of Kerkyra

Corfu, Greece

Location

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

Ioannina, Greece

Location

Department of Internal Medicine, University General Hospital of Larissa,

Larissa, Greece

Location

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

Pátrai, 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, Greece

Location

1st Department of Internal Medicine, PAPAGEORGIOU General Hospital of Thessaloniki

Thessaloniki, Greece

Location

2nd Department of Propedeutic Medicine, Ippokrateion University General Hospital of Thessaloniki

Thessaloniki, Greece

Location

3rd University Department of Internal Medicine, PAPAGEORGIOU General Hospital of Thessaloniki

Thessaloniki, Greece

Location

Dipartimento di Medicina Dipartimento di Malattie Infettive, ASST Spedali civili

Brescia, Italy

Location

Unità Operativa Clinica Malattie Infettive, Ospedale Policlinico San Martino

Genova, Italy

Location

Dipartimento di Medicina Interna, Istituto Clinico Humanitas

Milan, Italy

Location

Medicina Interna, Reumatologia, Immunologia, IRCCS San Raffaele

Milan, Italy

Location

Dipartimento di Malattie Infettive e Tropicali e Microbiologia, IRCCS Ospedale Sacro Cuore Don Calabria

Negrar, Italy

Location

Dipartimento di Malattie Infettive ad alta Intensità di cura ed altamente contagiose, IRCCS Lazzaro Spallanzani

Roma, Italy

Location

Dipartimento Scienze di laboratorio e infettivologiche, Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Dipartimento di Malattie infettive e tropicali-Università dell'Insubria, ASST dei Sette Laghi

Varese, Italy

Location

Related Publications (4)

• Kyriazopoulou E, Kotsaki A, Safarika A, Poulakou G, Milionis H, Metallidis S, Adamis G, Fragkou A, Rapti A, Del Vecchio P, Kalomenidis I, Kitzoglou D, Angheben A, Kainis I, Iliopoulou K, Serino FS, Bakakos P, Tzavara V, Ioannou S, Dagna L, Dimakou K, Tzatzagou G, Chini M, Bassetti M, Kotsis V, Tsoukalas G, Selmi C, Nikolakopoulou S, Samarkos M, Doumas M, Masgala A, Papanikolaou I, Argyraki A, Akinosoglou K, Symbardi S, Panagopoulos P, Dalekos GN, Liesenfeld O, Sweeney TE, Khatri P, Giamarellos-Bourboulis EJ. 29-mRNA host response signatures for classification of bacterial infection, viral infection and disease progression in COVID-19 pneumonia: a post hoc analysis of the SAVE-MORE randomized clinical trial. Intensive Care Med Exp. 2025 Jun 30;13(1):67. doi: 10.1186/s40635-025-00777-1.

  PMID: 40583075 DERIVED

• Kyriazopoulou E, Hasin-Brumshtein Y, Midic U, Poulakou G, Milionis H, Metallidis S, Astriti M, Fragkou A, Rapti A, Taddei E, Kalomenidis I, Chrysos G, Angheben A, Kainis I, Alexiou Z, Castelli F, Serino FS, Bakakos P, Nicastri E, Tzavara V, Ioannou S, Dagna L, Dimakou K, Tzatzagou G, Chini M, Bassetti M, Kotsis V, Tsoukalas DG, Selmi C, Konstantinou A, Samarkos M, Doumas M, Masgala A, Pagkratis K, Argyraki A, Akinosoglou K, Symbardi S, Netea MG, Panagopoulos P, Dalekos GN, Liesenfeld O, Sweeney TE, Khatri P, Giamarellos-Bourboulis EJ. Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial. Crit Care. 2024 Mar 12;28(1):73. doi: 10.1186/s13054-024-04852-z.

  PMID: 38475786 DERIVED

• Akinosoglou K, Kotsaki A, Gounaridi IM, Christaki E, Metallidis S, Adamis G, Fragkou A, Fantoni M, Rapti A, Kalomenidis I, Chrysos G, Boni G, Kainis I, Alexiou Z, Castelli F, Serino FS, Bakakos P, Nicastri E, Tzavara V, Safarika A, Ioannou S, Dagna L, Dimakou K, Tzatzagou G, Chini M, Bassetti M, Kotsis V, Angheben A, Tsoukalas G, Selmi C, Spiropoulou OM, Samarkos M, Doumas M, Damoraki G, Masgala A, Papanikolaou I, Argyraki A, Negri M, Leventogiannis K, Sympardi S, Gatselis NK, Petrakis V, Netea MG, Panagopoulos P, Sakka V, Milionis H, Dalekos GN, Giamarellos-Bourboulis EJ. Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: A subgroup analysis of the SAVE-MORE randomised trial. EClinicalMedicine. 2023 Feb;56:101785. doi: 10.1016/j.eclinm.2022.101785. Epub 2022 Dec 26.

  PMID: 36590789 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

MeSH Terms

Conditions

COVID-19

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus 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

• Evangelos Giamarellos-Bourboulis, MD, PhD

  Hellenic Institute for the Study of Sepsis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The SAVE-MORE is a pivotal, confirmatory, phase III randomized clinical trial (RCT) aiming to evaluate the efficacy and safety of early start of anakinra guided by suPAR in patients with LRTI by SARS-CoV-2 in improving the clinical state of COVID-19 over 28 days as measured by the ordinal scale of the 11-point WHO clinical progression scale (CPS).

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 23, 2020
• Study Start: December 23, 2020
• Primary Completion: March 31, 2021
• Study Completion: February 6, 2022
• Last Updated: September 6, 2022

Record last verified: 2022-09

Locations

IT (8); GR (32)