Treatment of COVID-19 Patients With Anti-interleukin Drugs

NCT04330638 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: COV-AID
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6 and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome

Conditions

COVID-19

Keywords

Acute Lung Injury; Hypoxia; Acute Respiratory Distress Syndrome; Corona virus; COVID-19; SARS (Severe Acute Respiratory Syndrome); Systemic Cytokine release Syndrome

Outcome Measures

Primary Outcomes (1)

• Time to Clinical Improvement

  Time to Clinical Improvement is defined as the time from randomization to either an increase of at least two points on a six category ordinal scale from the status at randomization or live discharge from the hospital.The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome

  at day 15

Secondary Outcomes (13)

• Time Untill Discharge

  during hospital admission (up to 28 days)

• Time Until Independence From Supplemental Oxygen or Discharge

  during hospital admission (up to 28 days)

• Time Until Independence From Invasive Ventilation

  during hospital admission (up to 54 days)

• Number of Days in ICU

  during hospital admission (up to 28 days)

• Number of Days in ICU in Patients Ventilated at Day of Randomization

  during hospital admission (up to 28 days)

Study Arms (6)

Usual Care

PLACEBO COMPARATOR

Other: Usual Care

Anakinra

ACTIVE COMPARATOR

Drug: Anakinra

Siltuximab

ACTIVE COMPARATOR

Drug: Siltuximab

Anakinra + Siltuximab

ACTIVE COMPARATOR

Drug: Anakinra; Drug: Siltuximab

Tocilizumab

ACTIVE COMPARATOR

Drug: Tocilizumab

Anakinra + Tocilizumab

ACTIVE COMPARATOR

Drug: Anakinra; Drug: Tocilizumab

Interventions

Usual Care OTHER

Usual Care

Usual Care

Anakinra DRUG

Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first

Also known as: KINERET®

Anakinra; Anakinra + Siltuximab; Anakinra + Tocilizumab

Siltuximab DRUG

Siltuximab will be given via single IV infusion at a dose of 11 mg/kg

Also known as: SYLVANT®

Anakinra + Siltuximab; Siltuximab

Tocilizumab DRUG

Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection

Also known as: ROACTEMRA®

Anakinra + Tocilizumab; Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recent ( ≥ 6 days of flu-like symptoms or malaise yet ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
• Confident COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period.
• In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (\<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion.
• Presence of hypoxia defined as PaO2/FiO2 below 350 while breathing room air in upright position or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation
• signs of cytokine release syndrome defined as ANY of the following:
• serum ferritin concentration \>1000 mcg/L and rising since last 24h
• single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device or mechanical ventilation
• lymphopenia defined as \<800 lymphocytes/microliter) and two of the following extra criteria
• Ferritin \> 700 mcg/L and rising since last 24h
• increased LDH (above 300 IU/L) and rising last 24h
• D-Dimers \> 1000 ng/mL and rising since last 24h
• CRP above 70mg/L and rising since last 24h and absence of bacterial infection
• if three of the above are present at admission, no need to document 24h rise
• Chest X-ray or CT scan showing bilateral infiltrates within last 2 days
• Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients

You may not qualify if:

• Patients with known history of serious allergic reactions, including anaphylaxis, to any of the study medications, or any component of the product.
• mechanical ventilation \> 24 h at Randomization
• Patient on ECMO at time of screening
• clinical frailty scale above 3 (This frailty score is the patient status before first symptoms of COVID-19 episode.)
• active bacterial or fungal infection
• unlikely to survive beyond 48h
• neutrophil count below 1500 cells/microliter
• platelets below 50.000/microliter
• Patients enrolled in another investigational drug study
• patients on high dose systemic steroids (\> 20 mg methylprednisolone or equivalent) for COVID-19 unrelated disorder
• patients on immunosuppressant or immunomodulatory drugs
• patients on current anti-IL1 or anti-IL6 treatment
• signs of active tuberculosis
• serum transaminase levels \>5 times upper limit of normal
• bowel perforation or diverticulitis

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Belgium Health Care Knowledge Centre: collaborator

Study Sites (15)

AZ Sint-Jan Brugge

Bruges, 8000, Belgium

Location

University Hospital Saint-Pierre

Brussels, 1000, Belgium

Location

Erasmus University Hospital

Brussels, 1070, Belgium

Location

University Hospital Saint-Luc

Brussels, 1200, Belgium

Location

University Hospital Antwerp

Edegem, 2650, Belgium

Location

Ziekenhuis Oost-Limurg

Genk, 3600, Belgium

Location

AZ Sint-Lucas

Ghent, 9000, Belgium

Location

University Hospital Ghent

Ghent, 9000, Belgium

Location

Jessa ZH

Hasselt, 3500, Belgium

Location

University Hospital Brussels

Jette, 1090, Belgium

Location

CHU Tivoli

La Louvière, 7100, Belgium

Location

CHR de la Citadelle

Liège, 4000, Belgium

Location

University Hospital Liège

Liège, 4000, Belgium

Location

Cliniques Saint-Pierre Ottignies

Ottignies-Louvain-la-Neuve, 1340, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

Related Publications (4)

• Davidson M, Menon S, Chaimani A, Evrenoglou T, Ghosn L, Grana C, Henschke N, Cogo E, Villanueva G, Ferrand G, Riveros C, Bonnet H, Kapp P, Moran C, Devane D, Meerpohl JJ, Rada G, Hrobjartsson A, Grasselli G, Tovey D, Ravaud P, Boutron I. Interleukin-1 blocking agents for treating COVID-19. Cochrane Database Syst Rev. 2022 Jan 26;1(1):CD015308. doi: 10.1002/14651858.CD015308.

  PMID: 35080773 DERIVED

• Declercq J, Van Damme KFA, De Leeuw E, Maes B, Bosteels C, Tavernier SJ, De Buyser S, Colman R, Hites M, Verschelden G, Fivez T, Moerman F, Demedts IK, Dauby N, De Schryver N, Govaerts E, Vandecasteele SJ, Van Laethem J, Anguille S, van der Hilst J, Misset B, Slabbynck H, Wittebole X, Lienart F, Legrand C, Buyse M, Stevens D, Bauters F, Seys LJM, Aegerter H, Smole U, Bosteels V, Hoste L, Naesens L, Haerynck F, Vandekerckhove L, Depuydt P, van Braeckel E, Rottey S, Peene I, Van Der Straeten C, Hulstaert F, Lambrecht BN. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial. Lancet Respir Med. 2021 Dec;9(12):1427-1438. doi: 10.1016/S2213-2600(21)00377-5. Epub 2021 Oct 29.

  PMID: 34756178 DERIVED

• Brands X, de Vries FMC, Uhel F, Haak BW, Peters-Sengers H, Schuurman AR, van Engelen TSR, Lutter R, Cremer OL, Bonten MJ, Schultz MJ, Scicluna BP, van der Poll T; MARS Consortium. Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia. Crit Care Med. 2021 Nov 1;49(11):1901-1911. doi: 10.1097/CCM.0000000000005072.

  PMID: 33935163 DERIVED

• Maes B, Bosteels C, De Leeuw E, Declercq J, Van Damme K, Delporte A, Demeyere B, Vermeersch S, Vuylsteke M, Willaert J, Bolle L, Vanbiervliet Y, Decuypere J, Libeer F, Vandecasteele S, Peene I, Lambrecht B. Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 3;21(1):468. doi: 10.1186/s13063-020-04453-5.

  PMID: 32493441 DERIVED

MeSH Terms

Conditions

COVID-19; Acute Lung Injury; Hypoxia; Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome

Interventions

Interleukin 1 Receptor Antagonist Protein; siltuximab; tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Anja Delporte
• Organization: UZ Gent

anja.delporte@uzgent.be

+3293320228

Study Officials

• Bart Lambrecht, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Pulmonology, Director VIB-Inflammational Research Center

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 1, 2020
• Study Start: April 3, 2020
• Primary Completion: December 20, 2020
• Study Completion: May 21, 2021
• Last Updated: March 14, 2023
• Results First Posted: March 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (15)