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Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID-19 Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04329650
Recruitment Status : Recruiting
First Posted : April 1, 2020
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Judit Pich Martínez, Fundacion Clinic per a la Recerca Biomédica

Brief Summary:
In our center up to 25% of the hospitalized patients with COVID-19 progress and need an intensive care unit. It is urgent to find measures that can avoid this progression to severe stages of the disease. We hypothesize that the use of anti-inflammatory drugs used at the time they start hyperinflammation episodes could improve symptoms and prognosis of patients and prevent their progression sufficiently to avoid their need for be admitted to an Intensive Care Unit.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Siltuximab Drug: Methylprednisolone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2, Randomized, Open-label Study to Compare Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID19 Pneumonia
Actual Study Start Date : April 15, 2020
Estimated Primary Completion Date : May 20, 2020
Estimated Study Completion Date : May 20, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Siltuximab 11mg/Kg Drug: Siltuximab
A single-dose of 11mg/Kg of siltuximab will be administered by intravenous infusion.

Active Comparator: Methylprednisolone 250mg/24h Drug: Methylprednisolone

A dose of 250mg/24 hours of methylprednisolone during 3 days followed by 30mg/24 hours during 3 days will be administered by intravenous infusion.

If the patient is taken lopinavir/ritonavir, the dose will be 125 mg/ 24 hours during 3 days followed by 15mg/24 hours during 3 days.





Primary Outcome Measures :
  1. Proportion of patients requiring ICU admission at any time within the study period. [ Time Frame: 29 days ]

Secondary Outcome Measures :
  1. Days of stay in the ICU during the study period. [ Time Frame: 29 days ]
  2. Days until resolution of fever defined as body temperature (axillary ≤ 36.6 ° C, oral ≤ 37.2 ° C, or rectal or tympanic ≤ 37.8 ° C) for at least 48 hours, without administration of antipyretics or until hospital discharge. [ Time Frame: 29 days ]
  3. Proportion of patients with a worsening requirement of supplemental oxygen at 29 days. days. [ Time Frame: 29 days ]
  4. Days with hypoxemia (SpO2 <93% in ambient air or requiring oxygen supplemental or mechanical ventilation support) at 29 days. [ Time Frame: 29 days ]
  5. Proportion of patients using mechanical ventilation at 29 days. [ Time Frame: 29 days ]
  6. Days with use of mechanical ventilation at 29 days. [ Time Frame: 29 days ]
  7. Days until the start of use of mechanical ventilation, non-invasive ventilation or use of high flow nasal cannula (if the patient have not previously required these interventions at the inclusion of the study) at 29 days. [ Time Frame: 29 days ]
  8. Days of hospitalization among survivors at 29 days. [ Time Frame: 29 days ]
  9. Mortality rate from any cause at 29 days. [ Time Frame: 29 days ]
  10. Proportion of patients with serious adverse events at 29 days. [ Time Frame: 29 days ]
  11. Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic with grade 4 neutropenia (count neutrophil absolute <500 / mm3) at 29 days. [ Time Frame: 29 days ]
  12. Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic at 29 days. [ Time Frame: 29 days ]
  13. Proportion of patients with grade 2 or higher adverse reactions related to the infusion of the sudy treatments at 29 days. [ Time Frame: 29 days ]
  14. Proportion of patients with hypersensitivity reactions of grade 2 or higher related to the administration of the study treatments at 29 days. [ Time Frame: 29 days ]
  15. Proportion of patients with gastrointestinal perforation at 29 days. [ Time Frame: 29 days ]
  16. Proportion of patients with secondary severe infections confirmed by laboratory or worsening of existing infections at 29 days. [ Time Frame: 29 days ]
  17. Changes from baseline in plasma leukocyte levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  18. Changes from baseline in plasma hemoglobin levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  19. Changes from baseline in plasma platelet at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  20. Changes from baseline in plasma creatinine levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  21. Changes from baseline in plasma total bilirubin levels at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  22. Proportion of patients with ALT≥ 3 times ULN (for patients with initial values normal) or> 3 times ULN AND at least 2 times more than the initial value (for patients with abnormal initial values) at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  23. Changes from baseline in plasma biomarkers (PCR, lymphocytes, ferritin, d-dimer and LDH) at days 1, 3, 5, 7 and 9. [ Time Frame: Days 1, 3, 5, 7 and 9 ]
  24. Changes from baseline in chest Rx at days 1, 3 and 5. [ Time Frame: Days 1, 3 and 5 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years old.
  2. Hospitalized patient (or documentation of a hospitalization plan if the patient is in an emergency department) with illness of more than 5 days of duration with evidence of pneumonia by chest radiography / tomography computed chest and meets at least one of the following requirements:

    1. Non-critical patient with pneumonia in radiological progression and / or
    2. Patient with progressive respiratory failure at the last 24-48 hours.
  3. Laboratory confirmed SARS-CoV-2 infection (by PCR) or other commercialized analysis or public health in any sample collected 4 days before the randomization or COVID-19 criteria following the defined diagnostic criteria at that time in the center.
  4. Patient with a maximum O2 support of 35%
  5. Be willing and able to comply with the study related procedures / evaluations.
  6. Women of childbearing potential * should have a negative serum pregnancy test before enrollment in the study and must commit to using methods highly effective contraceptives (intrauterine device, bilateral tubal occlusion, vasectomized couple and sexual abstinence).
  7. Written informed consent. In case of inability of the patient to sign the informed consent, a verbal informed consent from the legal representative or family witness (or failing this, an impartial witness outside the investigator team) will be obtained by phone.

When circumstances so allow, participants should sign the consent form. The confirmation of the verbal informed consent will be documented in a document as evidence that verbal consent has been obtained.

Exclusion Criteria:

  1. Patient who, in the investigator's opinion, is unlikely to survive> 48 hours after the inclusion in the study.
  2. Presence of any of the following abnormal analytical values at the time of the inclusion in the study:

    • absolute neutrophil count less than 2000 / mm3;
    • AST or ALT> 5 times the upper limit of normality;
    • platelets <50,000 per mm3.
  3. In active treatment with immunosuppressants or previous prolonged treatment (more 3 months) of oral corticosteroids for a disease not related to COVID-19 at a dose greater than 10 mg of prednisone or equivalent per day.
  4. Known active tuberculosis or known history of tuberculosis uncompleted treatment.
  5. Patients with active systemic bacterial and / or fungal infections.
  6. Patients who have received previous treatment with IL6 inhibitor (tocilizumab, sarilumab).
  7. Participants who, at the investigator's discretion, are not eligible to participate, regardless of the reason, including medical or clinical conditions, or participants potentially at risk of not following study procedures.
  8. Patients who do not have entry criteria in the Intensive Care Unit.
  9. Pregnancy or lactation.
  10. Known hypersensitivity to siltuximab or to any of its excipients (histidine, histidine hydrochloride, polysorbate 80 and sucrose).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04329650


Contacts
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Contact: Felipe García, MD +34932275400 ext 2884 fgarcia@clinic.cat

Locations
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Spain
Hospital Germans Trias i Pujol Not yet recruiting
Badalona, Spain
Contact: Roger Paredes, MD         
Principal Investigator: Roger Paredes, MD         
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Felipe García, MD         
Principal Investigator: Felipe García, MD         
Principal Investigator: Alex Soriano, MD         
Hospital Universitario de Salamanca Not yet recruiting
Salamanca, Spain
Contact: Cristina Carbonell, MD         
Principal Investigator: Cristina Carbonell, MD         
Hospital Universitari Mútua de Terrassa Not yet recruiting
Terrassa, Spain
Contact: David Dalmau, MD         
Principal Investigator: David Dalmau, MD         
Sponsors and Collaborators
Judit Pich Martínez
Investigators
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Principal Investigator: Felipe García, MD Hospital Clínic de Barcelona
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Responsible Party: Judit Pich Martínez, Clinical Research Manager, Fundacion Clinic per a la Recerca Biomédica
ClinicalTrials.gov Identifier: NCT04329650    
Other Study ID Numbers: SILCOR-COVID-19
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: April 17, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Siltuximab
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents