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Covid-19Phase 2NCT04412291

A Study in Patients With COVID-19 and Respiratory Distress Not Requiring Mechanical Ventilation, to Compare Standard-of-care With Anakinra and Tocilizumab Treatment The Immunomodulation-CoV Assessment (ImmCoVA) Study

A Phase 2 study testing Anakinra Prefilled Syringe, Tocilizumab Prefilled Syringe and Standard-of-care treatment in people with Covid-19, run by Karolinska University Hospital at 1 site in Sweden.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The study is designed as a randomized, controlled, multi-center open-label trial to compare standard-of-care (SOC) treatment with SOC + anakinra or SOC + tocilizumab treatment in hospitalized adult subjects who are diagnosed with severe COVID 19. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid-19
What is being tested?
Anakinra Prefilled Syringe, Tocilizumab Prefilled Syringe and Standard-of-care treatment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteSweden
Study dates
11 Jun 2020to Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years
  • Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay < 7 days prior to screening
  • SARS-CoV-2 infection with duration at least 7 days (i e may be included on day 7) as determined by onset of symptoms (defined as day 1)
  • 5 liters/minute of Oxygen for at least 8 hours to maintain SpO2 at ≥93%. A shorter duration is also accepted if presentation is acute, and the patient needs more than 10 liters/minute of Oxygen, or high flow nasal cannula or non-invasive ventilation, to maintain SpO2 at ≥93%..
  • CRP > 70 mg/L with no non-SARS-Cov2 infections. Values measured up to 48 hours before inclusion are accepted.
  • Ferritin > 500 µg/L Values measured up to 48 hours before inclusion are accepted.
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  • At least two points on a scale of 0-3 where 1 point is awarded for each value of; lymphocytes < 1x 10(9)/L; D-dimer ≥ 0.5 mg/L and; Lactate Dehydrogenase ≥ 8 microkatal/L. The values do not have to be concurrently positive and may be up to 3 days old at inclusion.
  • Ability to provide informed consent signed by study patient
  • Willingness and ability to comply with study-related procedures/assessments
  • In fertile females, willing to comply with effective contraceptive methods for up to 3 months after last dose of study drug. These may include surgical sterilization of patient or partner, intrauterine device or condoms. Gestagen-only birth control pills (mini-pills), which do not increase the risk of deep venous thrombosis, may also be used. Non-fertile woman is defined as more than 12 months of amenorrhea without an alternative medical cause or, in case of ambiguities, an FSH level in the postmenopausal range.

Who cannot join

  • Pregnancy or breast feeding.
  • Ongoing or completed mechanical ventilation.
  • In the opinion of the investigator, unlikely to survive for >48 hours from screening.
  • In the opinion of the investigator, expected overall survival due to other comorbidities less than 3 months.
  • Severe renal dysfunction eGFR < 30 ml/min.
  • Medical history including chronic liver disease with inflammation, fibrosis or cirrhosis including underlying diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis, alcoholic liver disease, autoimmune liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis, or carcinoma.
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  • Uncontrolled hypertension Systolic BP >180 mm Hg, Diastolic BP > 110 mm Hg.
  • History of hypersensitivity to the study drugs
  • Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2 x 109/L, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN), platelets <100 x 109/L
  • Treatment with anakinra, anti-IL 6, anti-IL-6R antagonists, Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
  • Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents
  • Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day. Ongoing acute treatment for COVID-19 with any peroral or iv steroid is permitted for up to five days before inclusion. Chronic or acute treatment with inhaled steroids is also permitted
  • History of, or current autoimmune or inflammatory systemic or localized disease(s) other than rheumatoid arthritis
  • Acute systemic infection; verified by blood cultures systemic bacterial infection, systemic fungi-infection or prosthesis-related infection
  • History of stem-cell or solid organ transplantation
  • Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
  • Diagnosis of, or suspicion of HIV infection, acute hepatitis A and/or chronic hepatitis B and/or C
  • Previous history of gastrointestinal ulceration or diverticulitis.
  • Patients who have received immunosuppressive antibody therapy within the past 3 months, including intravenous immunoglobulin or plans to receive during the study period
  • Participation in any clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. The use of remdesivir is permitted.
  • 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

Trial locations and contacts

1 site in 1 country.

Investigator Jonas Sundén-Cullberg, MD PhD contact

+46-8-58580000

Jonas.sunden-cullberg@sll.se

Jon Lampa, MD PhD contact

+46-8-58580000

jon.lampa@sll.se

Sweden1 site, 1 recruiting

  • Karolinska University Hospital

    Huddinge, Stockholm County, 141 86

    Jonas Sundén-Cullberg, MD, PHD, jonas.sunden-cullberg@sll.se

    Recruiting

Other trials in Sweden

About this study

Official title: A Multi-center, Randomized, Open-label Study in Patients With COVID-19 and Respiratory Distress Not Requiring Mechanical Ventilation, to Compare Standard-of-care With Anakinra and Tocilizumab Treatment The Immunomodulation-CoV Assessment (ImmCoVA) Study

The study is designed as a randomized, controlled, multi-center open-label trial to compare standard-of-care (SOC) treatment with SOC + anakinra or SOC + tocilizumab treatment in hospitalized adult subjects who are diagnosed with severe COVID 19.

Arm A: Standard-of-care Treatment (SOC) Arm B: Anakinra + SOC Arm C: Tocilizumab + SOC.

All subjects will be treated with standard-of-care treatment. Arms B and C will also receive broad spectrum antibiotics initiated before or latest 24 hours after initiation of treatment with study drug.

The primary follow-up period of the study is 29 days.

Conditions
Covid-19
Being tested
Anakinra Prefilled Syringe, Tocilizumab Prefilled Syringe, Standard-of-care treatment
Keywords
Coronavirus 2, SARS-CoV-2, Anakinra, Tocilizumab
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anakinra Prefilled SyringeDrug

    A total dose of 400mg per day (divided in 4 doses of 100 mg iv every 6 hours) for 7 days.

  • Tocilizumab Prefilled SyringeDrug

    8mg/kg for a single infusion iv up to max 800 mg. If no clinical response is obtained, another dose of 8mg/kg may be administered after earliest 2 days after inclusion with the following condition: The clinical symptoms are worsened (as assessed by decreasing PaO2/FiO2 and/or need of increased ventilatory support such as NIV, HFNC or mechanical ventilation).

  • Standard-of-care treatmentDrug

    Also called Oxygen supplementation, Thrombosis prophylaxis, Steroids, Antibiotics

    SOC according to local recommendations at the Karolinska University Hospital. Oxygen supplementation so to achieve SpO2>93%. Thrombosis prophylaxis (Fragmin or Innohep and Klexane® or new oral anticoagulants including dabigatran, apixaban or rivaroxaban).

    Steroids (Betapred 6 mg po) Broad spectrum antibiotics (only in arm B and C)

Study groups in NCT04412291
Study groupRoleWhat they receive
Standard-of-care Treatment (SOC)Active comparatorSOC according to local recommendations at the Karolinska University Hospital: Oxygen supplementation so to achieve SpO2>93%. Thrombosis prophylaxis (Fragmin or Innohep or Klexane or new oral anticoagulants incl. dabigatran, apixaban or rivaroxaban). Steroids (Betapred)
Receives: Drug: Standard-of-care treatment
Anakinra + SOCActive comparatorAnakinra: A total dose of 400mg per day (divided in 4 doses of 100 mg iv every 6 hours) for 7 days. SOC according to local recommendations at the Karolinska University Hospital. Oxygen supplementation so to achieve SpO2>93%. Thrombosis prophylaxis (Fragmin or Innohep) Steroids (Betapred) Prophylactic broad spectrum antibiotics for seven days..
Receives: Drug: Anakinra Prefilled Syringe; Drug: Standard-of-care treatment
Tocilizumab + SOC.Active comparatorTocilizumab: 8mg/kg for a single infusion iv up to max 800 mg. If no clinical response is obtained, another dose of 8mg/kg may be administered after earliest 2 days SOC according to local recommendations at the Karolinska University Hospital. Oxygen supplementation so to achieve SpO2>93%. Thrombosis prophylaxis (Fragmin or Innohep) Steroids (Betapred) Prophylactic broad spectrum antibiotics for seven days.
Receives: Drug: Tocilizumab Prefilled Syringe; Drug: Standard-of-care treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to recovery

    Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 1; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

    1 LMWH-injections (Fragmin, Innohep) do not count as medical care

    Measured: Day 1 through Day 29

Secondary outcomes (33)

  1. Mortality

    Measured: Up to day 29

  2. Number of Days on mechanical ventilation

    Measured: Up to day 29

  3. Number of days of supplemental oxygen use

    Measured: Up to day 29

  4. Number of patients requiring initiation of mechanical ventilation

    Measured: Up to day 29

  5. Time to improvement in oxygenation for at least 48 hours

    Definition of improvement in oxygenation: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measured: Up to day 29

  6. Mean change in the 8-point ordinal scale

    8-point Ordinal Scale:

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow nasal cannula;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen;
    8. Not hospitalized

    Measured: Up to day 15

  7. Proportion of patients on level e-h on the 8-point ordinal scale at day 15

    8-point Ordinal Scale:

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow nasal cannula;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen;
    8. Not hospitalized

    Measured: Day 15

  8. Time to improvement in one category from baseline using the 8-point ordinal scale

    8-point Ordinal Scale:

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow nasal cannula;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen;
    8. Not hospitalized

    Measured: Up to day 29

  9. Mean change in Sequential organ failure assessment score (SOFA)

    Measured: Up to day 15

  10. Time to resolution of fever for at least 48 hours by clinical severity

    Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic)

    Measured: Up to day 29

  11. Time to improvement of three points from baseline in National Early Warning Score 2 (NEWS2) scoring system

    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)

    Measured: Up to day 29

  12. Time to score of <2 maintained for 24 hours in NEWS2 scoring system (National Early Warning Score)

    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)

    Measured: Up to day 29

  13. Mean change in NEWS2 scoring system (National Early Warning Score)

    Measured: Up to day 15

  14. Number of days with fever.

    Based on highest measured daily body temperature. Defined as >36.6°C (axilla), >37.2°C (oral) or >37.8°C (rectal or tympanic

    Measured: Up to day 29

  15. Number of days of resting respiratory rate >24 breaths/min

    Based on highest respiratory rate measured between 06.00 and 09.00 each day

    Measured: Up to day 29

  16. Time to saturation ≥94% on room air

    Measured: Up to day 29

  17. Cumulative dose of steroids; equivalent to betamethasone dosage (mg)

    Measured: From start of steroid treatment for Covid-19 up to day 29

  18. Cumulative dose of steroids during the study; equivalent to betamethasone dosage (mg)

    Measured: From day 1 up to day 29

  19. Incidence of serious adverse events

    Measured: Up to day 60

  20. Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection

    Measured: Up to day 29

  21. Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with grade 4 neutropenia

    Measured: Up to day 60

  22. Incidence of hypersensitivity reactions

    Measured: Up to day 29

  23. Incidence of infusion reactions

    Measured: Up to day 29

  24. Number of ventilator free days in the first 28 days

    Measured: Baseline to day 29

  25. Number of patients requiring non-invasive ventilation

    Measured: Up to day 29

  26. Number of patients requiring the use of high flow nasal cannula

    Measured: Up to day 29

  27. Number of patients requiring Extracorporeal membrane oxygenation (ECMO)

    Measured: Up to day 29

  28. Number of patients that have been admitted into an intensive care unit (ICU)

    Measured: Up to day 29

  29. Number of patients that have been admitted into a High Dependency Unit ("Intermediärvårdsavdelning")

    Measured: Up to day 29

  30. Number of days admitted into a High Dependency Unit ("Intermediärvårdsavdelning") or intensive care unit (ICU) [

    Measured: Up to day 29

  31. Number of days of hospitalization in survivors

    Measured: Up to day 29

  32. Number of patients discharged to institution other than normal domicile.

    Measured: Up to day 60

  33. Number of deaths due to any cause

    Measured: Up to day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2020
  2. Study start11 Jun 2020
  3. Primary completionMar 2021 (estimated)
  4. Study completionJun 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04412291
Sponsor's protocol ID
2020-001748-24
Status last verified
Feb 2021
First submitted
1 Jun 2020
Last updated
18 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Sunden-Cullberg J, Chen P, Habel H, Skorup P, Janols H, Rasmuson J, Niward K, Ostholm Balkhed A, Chatzidionysiou K, Asgeirsson H, Blennow O, Parke A, Svensson AK, Muvva JR, Ljunggren HG; Karolinska KI/K COVID-19 Treatment Working Group; Horne AC, Aden U, Henter JI, Sonnerborg A, Vesterbacka J, Nowak P, Lampa J. Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial. PLoS One. 2023 Dec 29;18(12):e0295838. doi: 10.1371/journal.pone.0295838. eCollection 2023.

    PubMed 38157348

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra Prefilled Syringe, Tocilizumab Prefilled Syringe and Standard-of-care treatment in people with Covid-19, run by Karolinska University Hospital at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Investigator Jonas Sundén-Cullberg, MD PhD (+46-8-58580000, Jonas.sunden-cullberg@sll.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to recovery (time frame: Day 1 through Day 29). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04412291, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2021.

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