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Effectiveness of Interleukin-6 Receptor Inhibitors in the Management of Patients With Severe SARS-CoV-2 Pneumonia: An Open-Label, Multicenter Sequential and Cluster Randomized Trial

Trial Profile

Effectiveness of Interleukin-6 Receptor Inhibitors in the Management of Patients With Severe SARS-CoV-2 Pneumonia: An Open-Label, Multicenter Sequential and Cluster Randomized Trial

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 06 May 2020

At a glance

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

    • 05 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 01 Apr 2020 Planned initiation date changed from 25 Mar 2020 to 4 Apr 2020.
    • 31 Mar 2020 New trial record

Trial Overview

Purpose

To compare the effect of either one of three IL-6 inhibitor administrations, relative to the standard of care, on time to independence from supplementary oxygen therapy, measured in days from baseline to day 28, in patients with severe SARS-CoV-2 pneumonia.

Primary Endpoints

Time to independence from supplementary oxygen therapy

time_frame: days from enrolment up 28 days

Other Endpoints

Number of deaths

time_frame: 28 days from enrolment

Days out of hospital and alive

time_frame: 28 days from enrolment

Ventilator free days alive and out of hospital

time_frame: 28 days from enrolment

C-reactive protein (CRP) level

description: Measured from standard blood test
time_frame: baseline
time_frame: peak during hospitalisation, up to 28 days
time_frame: 14 days
time_frame: 28 days

Number of participants with serious adverse events

description: Measured as occurrence of any serious adverse events
time_frame: During treatment, up to 28 days [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Pneumonia treatment severe
Severe acute respiratory syndrome treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 200

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

Patient Inclusion Criteria

- SARS-CoV-2 infection confirmed by real time-PCR and - Positive imaging: consolidation, ground glass opacities, or bilateral pulmonary infiltration either by CT-scan or chest x-ray; and - Need of oxygen therapy to maintain SO2>94% OR FiO2/PaO2 > 20 and at least two of the following laboratory measures: - CRP level >70 mg/L - CRP level ≥ 40 mg/L and doubled within 48 hours (without other confirmed infectious or non-infectious course), - Lactatdehydrogenase > 250 U/L, - thrombocytopenia < 120.000 x 10E9/L, - lymphocyte count < 0.6 x 10E9/L, - D-dimer > 1 ug/mL, - serum ferritin > 300 ug/mL

Patient Exclusion Criteria

- pregnancy suspected or confirmed, - severe heart failure, - suspected or confirmed bacterial infection, - current solid or hematological malignancy, - neutropenia, - ALAT elevation more than three times the laboratory upper limit, - ASA class 5 (after COVID19 admission) or higher at inclusion (prior admission), - severe chronic obstructive pulmonary disease or heart failure (NYHA class II or higher), - pregnant or lactating women, - current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents including IL-6 inhibitors, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period, - current use of chronic oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, - previous or active tuberculosis (TB), - HIV infection regardless of immunological status, hepatitis, - evidence of recent (30 days) invasive bacterial or fungal infections, - patients who have received immunosuppressive antibody therapy within the past 5 months, including intravenous immunoglobulin or plans to receive during the study period, - IV drug abuse, - history of inflammatory bowel disease, - diverticulitis, - ulcer, - perforated gastrointestinal tract, - participation in any clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than five half-lives of IP prior inclusion to the study, - any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study, - inability to give informed consent.

Trial Details

Identifiers

Identifier Owner
NCT04322773 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001275-32 European Clinical Trials Database
APPI2CV2020-01 -

Trial Dates

  • Initiation Dates

    Planned : 04 Apr 2020

    Actual : 05 Apr 2020

  • Primary Completion Dates

    Planned : 01 Jun 2021

  • End Dates

    Planned : 01 Jun 2021

Other Details

  • Design multicentre; open; prospective; randomised; sequential
  • Phase of Trial Phase II
  • Location Denmark
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
SarilumabPrimary Drug Subcutaneous Injection
TocilizumabPrimary Drug Intravenous Infusion
TocilizumabPrimary Drug Subcutaneous Injection

Roactemra iv

Single dose treatment with 400 mg tocilizumab intravensously
Drug: RoActemra iv (single dose treatment with tocilizumab 400 mg intravenously) Other Name: tocilizumab 400 mg
Other: Standard medical care (management as usual)

Roactemra sc

Single dose treatment with 2 x 162 mg tocilizumab subcutaneously
Drug: RoActemra sc (single dose treatment with tocilizumab 2 x 162 mg subcutaneously) Other Name: tocilizumab 2 x 162 mg
Other: Standard medical care (management as usual)

Kevzara sc

Single dose treatment with 1 x 200 mg sarilumab subcutaneously
Drug: Kevzara sc (single dose treatment with sarilumab 1 x 200 mg subcutaneously) Other Name: sarilumab 1 x 200 mg
Other: Standard medical care (management as usual)

Standard care

Management as usual
Other: Standard medical care (management as usual)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Lars Erik Kristensen, PhD
0045 38164157
lars.erik.kristensen@regionh.dk
show details
Bispebjerg-Frederiksberg Hospital Denmark
Line Rustad
0045 38164158
line.rustad@regionh.dk
show details
Bispebjerg-Frederiksberg Hospital Denmark

Centres

Centre Name Location Trial Centre Country
Bispebjerg-Frederiksberg Hospital Copenhagen Denmark
Lars Erik Kristensen
-
-
Marius Henriksen
-
-

Trial History

Event Date Event Type Comment
06 May 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 06 May 2020
08 Apr 2020 Other trial event Last checked against the ClinicalTrials.gov record. Updated 08 Apr 2020
07 Apr 2020 Other trial event New source identified and integrated(European Clinical Trials Database:EudraCT2020-001275-32). Updated 07 Apr 2020
05 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 08 Apr 2020
01 Apr 2020 Other trial event Planned initiation date changed from 25 Mar 2020 to 4 Apr 2020. Updated 06 Apr 2020
31 Mar 2020 New trial record New trial record Updated 31 Mar 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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