Efficiency in Management of Organ Dysfunction Associated With Infection by the Novel SARS-CoV-2 Virus (COVID-19) Through a Personalized Immunotherapy Approach: the ESCAPE Clinical Trial
Latest Information Update: 04 Nov 2021
At a glance
- Drugs Anakinra (Primary) ; Tocilizumab (Primary)
- Indications COVID-19 respiratory infection
- Focus Therapeutic Use
- Acronyms ESCAPE
- 08 Jan 2021 Status changed from active, no longer recruiting to completed.
- 04 Jan 2021 Status changed from recruiting to active, no longer recruiting.
- 14 Apr 2020 Status changed from not yet recruiting to recruiting.
Most Recent Events
Trial Overview
Purpose
Our aim is to conduct one trial of personalized immunotherapy in patients with SARS-CoV-2 associated with organ dysfunction and with laboratory findings of macrophage activation syndrome or immune dysregulation. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be allocated to immunotherapy treatment according to their needs.
Primary Endpoints
Change of baseline total sequential organ failure assessment (SOFA) score
description: At least 25% decrease between baseline sequential organ failure assessment SOFA score and measured sequential organ failure assessment SOFA score at Study Day 8
time_frame: Visit study day 8
Improvement of lung involvement measurements
description: Resolution of all criteria of lower respiratory tract involvemed that led to study inclusion (except findings from imaging studies) at Study Day 8
time_frame: Visit study day 8
Increase of pO2/FiO2 ratio
description: At least 50% increase of pO2/FiO2 ratio between baseline and study visit Day 8
time_frame: Visit Study Day 8
Other Endpoints
Comparison of change of baseline total sequential organ failure assessment (SOFA) score in enrolled subjects towards historical comparators
description: Change of total sequential organ failure assessment (SOFA) score between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
time_frame: Screening, Day 8
Comparison of change of lung involvement measurements in enrolled subjects towards historical comparators
description: Change of lung involvement measurements between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
time_frame: Screening, Day 8
Comparison of pO2/FiO2 ratio in enrolled subjects towards historical comparators
description: Comparison of increase in pO2/FiO2 ratio towards historical comparators from Hellenic Sepsis Study Group Database
time_frame: Screening, Day 8
Change of sequential organ failure assessment (SOFA) score
description: Change of Sequential organ failure assessment (SOFA) score on day 28 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
time_frame: Day 28
Rate of Mortality
description: Mortality on day 28
time_frame: Day 28
Rate of Mortality
description: Mortality on day 90
time_frame: Day 90
Cytokine stimulation
description: Cytokine stimulation from peripheral blood mononuclear cells will be compared between days 0 and 4
time_frame: Screening, Day 4
Gene expression
description: Gene expression of peripheral blood mononuclear cells will be compared between days 0 and 4
time_frame: Screening, Day 4
Serum/plasma proteins
description: Change of serum/plasma proteins between days 0 and 4
time_frame: Screening, Day 4
Classification of the immune function
description: Classification of immune function of screened patients who are not enrolled in study drug since they are not characterized with MAS or immune dysregulation
time_frame: Screening [1]
Diseases Treated
Indication | Qualifiers | Patient Segments |
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COVID-19 respiratory infection | treatment | - |
Biomarker
NCT Number | Biomarker Name | Biomarker Function |
---|---|---|
NCT04339712 | Ferritin | Eligibility Criteria |
HLA-DR | Eligibility Criteria | |
Monocyte differentiation antigen CD14 | Eligibility Criteria |
Subjects
- Subject Type patients
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Number
Planned: 40
Actual: 102
- Sex male & female
- Age Group ≥ 18 years; adult
Patient Inclusion Criteria
- 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 Organization11 - Organ dysfunction defined as the presence of at least one of the following conditions: - Total SOFA score greater than or equal to 2; - Involvement of the lower respiratory tract - Laboratory documentation of MAS or immune dysregulation. MAS is documented by the findings of any serum ferritin greater than 4,420ng/ml. immune dysregulation is documented by the combination of two findings: a) serum ferritin equal to or lower than 4,420ng/ml; and b) less than 5,000 receptors of the membrane molecule of HLA-DR on the cell membrane of blood CD14-monocytes or less than 30 MFI of HLA-DR on the cell membrane of blood CD14-monocytes as counted by flow cytometry
Patient Exclusion Criteria
- Age below 18 years - Denial for written informed consent - Any stage IV malignancy - Any do not resuscitate decision - Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB - Infection by the human immunodeficiency virus (HIV) - Any primary immunodeficiency - Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg prednisone or greater the last 15 days. - Any anti-cytokine biological treatment the last one month - Medical history of systemic lupus erythematosus - Medical history of multiple sclerosis or any other demyelinating disorder. - Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study
Trial Details
Identifiers
Identifier | Owner |
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NCT04339712 | ClinicalTrials.gov: US National Institutes of Health |
EudraCT2020-001039-29 | European Clinical Trials Database |
ESCAPE | - |
Trial Dates
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Initiation Dates
Planned : 06 Apr 2020
Actual : 02 Apr 2020
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Primary Completion Dates
Planned : 01 Apr 2022
Actual : 01 Dec 2020
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End Dates
Planned : 01 Apr 2022
Actual : 08 Jan 2021
Other Details
- Design multicentre; open; prospective
- Phase of Trial Phase II
- Location Greece
- Focus Therapeutic Use
Interventions
Drugs | Route | Formulation |
---|---|---|
AnakinraPrimary Drug | Intravenous |
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TocilizumabPrimary Drug | Intravenous | Infusion |
anakinra
In case of diagnosis of MAS, IV anakinra 200mg three times daily (every eight hours) for 7 days. Patients who will receive anakinra treatment and who suffer from kidney dysfunction will receive 50% of the dose i.e. 100mg anakinra three times daily for 15 days Drug: Anakinra (In case of diagnosis of MAS treatment with anakinra) Other Name: kineret
tocilizumab
In case of diagnosis of immune dysregulation IV tocilizumab 8mg/kg body weight once up to a maximum of 800mg. These patients will receive anakinra at the above dose in case they meet one of the following contra-indications for tocilizumab: absolute neutrophil count less than 2,500/mm3; absolute platelet count less than 100,000/mm3; and AST or ALT more than 1.5 x the upper normal limit Drug: Tocilizumab (In case of diagnosis of immune dysregulation treatment with tocilizumab) Other Name: RoActemra
Trial Centres
Investigators
Investigator | Centre Name | Trial Centre Country |
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Antigoni Kotsaki, MD, PhD
+306946637164 antigonebut@yahoo.com
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Apostolos Armaganidis, MD, PhD | National Kapodistrian University of Athens, Medical School |
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Evangelos Giamarellos-Bourboulis, MD, PhD
+302107480662 egiamarel@med.uoa.gr
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President of the Board
88 Michalakopoulou Street
show details
Athens Postcode: 111528 Greece Telephone: 302107480662 Fax: 302107480662 insepsis@otenet.gr |
HELLENIC INSTITUTE FOR THE STUDY OF SEPSIS | Greece |
Centres
Centre Name | Location | Trial Centre Country |
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- |
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1st Department of Pulmonary Medicine and Intensive Care Unit | Athens | Greece |
2nd Department of Critical Care Medicine, ATTIKON University Hospital | Athens, Haidari | Greece |
4th Department of Internal Medicine, Attikon University Hospital | Athens | Greece |
Department of Anesthesiology and Intensive Care Medicine, University General Hospital of Thessaloniki AHEPA | Thessaloniki | Greece |
Department of Internal Medicine, I PAMMAKARISTOS Hospital | Athens | Greece |
Department of Internal Medicine, Larissa University Hospital | Larissa | Greece |
Department of Internal Medicine, Patras University Hospital | Patras, Rion | Greece |
HELLENIC INSTITUTE FOR THE STUDY OF SEPSIS | Athens | Greece |
Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General Hospital | Larissa | Greece |
Intensive Care Unit, "Latsio", Thriasio Elefsis General Hospital | Elefsína | Greece |
Intensive Care Unit, AGIOS DIMITRIOS General Hospital of Thessaloniki | Thessaloniki | Greece |
Intensive Care Unit, G. GENNIMATAS General Hospital of Thessaloniki | Thessaloniki | Greece |
Intensive Care Unit, General Hospital ASKLEPIEIO Voulas | Athens | Greece |
Intensive Care Unit, General Hospital of Athens IPPOKRATEIO | Athens | Greece |
Intensive Care Unit, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S. | Athens | Greece |
Intensive Care Unit, General Hospital of Thessaloniki IPPOKRATEIO | Thessaloniki | Greece |
Intensive Care Unit, Ioannina University Hospital | Ioánnina, Ioannina | Greece |
Intensive Care Unit, Theageneio Oncological Hospital of Thessaloniki | Thessaloniki | Greece |
National Kapodistrian University of Athens, Medical School |
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Trial History
Event Date | Event Type | Comment |
---|---|---|
12 Jan 2021 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 12 Jan 2021 |
11 Jan 2021 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
08 Jan 2021 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 12 Jan 2021 |
04 Jan 2021 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 07 Jan 2021 |
15 Apr 2020 | Other trial event | New source identified and integrated (ClinicalTrials.gov record: NCT04339712). Updated 15 Apr 2020 |
15 Apr 2020 | Other trial event | Last checked against European Clinical Trials Database. Updated 15 Apr 2020 |
14 Apr 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 16 Apr 2020 |
12 Apr 2020 | Other trial event | Planned number of patients changed from 20 to 40. Updated 15 Apr 2020 |
07 Apr 2020 | New trial record | New trial record Updated 07 Apr 2020 |
06 Apr 2020 | Status change - not yet recruiting | Status changed from recruiting to not yet recruiting. Updated 15 Apr 2020 |
References
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ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
European Clinical Trials Database. Trial-Reg 2023;.
Available from: URL: https://www.clinicaltrialsregister.eu
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