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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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 23 Apr 2020

At a glance

  • Drugs Anakinra (Primary) ; Tocilizumab (Primary)
  • Indications COVID 2019 infections; Severe acute respiratory syndrome
  • Focus Therapeutic Use
  • Acronyms ESCAPE
  • Most Recent Events

    • 14 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 12 Apr 2020 Planned number of patients changed from 20 to 40.
    • 07 Apr 2020 New trial record

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
COVID 2019 infections treatment -
Severe acute respiratory syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 40

  • Sex male & female
  • Age Group ≥ 18 years; adult; elderly

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
NCT04339712 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001039-29 European Clinical Trials Database
ESCAPE -

Trial Dates

  • Initiation Dates

    Planned : 06 Apr 2020

    Actual : 02 Apr 2020

  • Primary Completion Dates

    Planned : 01 Apr 2022

  • End Dates

    Planned : 01 Apr 2022

Other Details

  • Design multicentre; open; prospective
  • Phase of Trial Phase II
  • Location Greece
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
AnakinraPrimary Drug Intravenous
-
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
Antigoni Kotsaki, MD, PhD
+306946637164 antigonebut@yahoo.com
show details
-
Apostolos Armaganidis, MD, PhD National Kapodistrian University of Athens, Medical School
-
Evangelos Giamarellos-Bourboulis, MD, PhD
+302107480662 egiamarel@med.uoa.gr
show details
-
President of the Board
88 Michalakopoulou Street
Athens
Postcode: 111528
Greece
Telephone: 302107480662
Fax: 302107480662
insepsis@otenet.gr
show details
HELLENIC INSTITUTE FOR THE STUDY OF SEPSIS Greece

Centres

Centre Name Location Trial Centre Country
-
-
-
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
-
-

Trial History

Event Date Event Type Comment
23 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 23 Apr 2020
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

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
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