Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to Covid-19 (ANA-COVID-GEAS)

NCT04443881 | Completed Phase 2

• 1 other identifier: ANA-COVID-GEAS
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 12

Brief Summary

Phase 2/3 randomized, parallel group, 2-arm study (treatment vs. control), investigating the efficacy and safety of intravenous administration of anakinra, an interleukin 1 receptor antagonist ( IL-1), added to standard treatment, compared to standard treatment alone, to reduce hyperinflammation and respiratory distress in patients with SARS-CoV-2 infection.

Conditions

COVID-19 Pnemonia

Keywords

Covid-19 disease; pneumonia; Cytokine Storm Sindrome; Anti IL-1; Anakinra

Outcome Measures

Primary Outcomes (5)

• Treatment success, defined as number of patients not requiring mechanical ventilation to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia.

  Treatment success, defined as number of patients not requiring mechanical ventilation by Day 15.

  Day 15

• Number of patients not requiring mechanical ventilation to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia.

  Number of patients not requiring mechanical ventilation

  Day 28

• Time to mechanical ventilation to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia.

  Time to mechanical ventilation

  Up to 28 days

• Time to oxygen saturation normalization to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia.

  Time to oxygen saturation normalization

  Up to 28 days

• Stay in ICU and hospitalization to assess the effect of anakinra in addition to standard treatment on the need for mechanical ventilation in patients with severe COVID-19 and CSS pneumonia.

  Stay in ICU and hospitalization

  Up to 28 days

Secondary Outcomes (4)

• Total mortality rate to assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia.

  day 28

• Mortality 48 hours, 7 days, in ICU and hospital to assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia.

  48 hours, 7 days

• Viral clearance / viral shedding to assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia.

  Up to 28 days

• To assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia.

  At day 28

Other Outcomes (9)

• Change in IL-6 to assess the effect of anakinra on IL-6, ferritin, and selected biomarkers relevant for hyperinflammation, MAS and cytokine storm change from baseline.

  During 28 days

• Change in ferritin to assess the effect of anakinra

  During 28 days

• Change in D-dimer to assess the effect of anakinra

  During 28 days

Study Arms (2)

Anakinra Arm

EXPERIMENTAL

Standard of care plus Anakinra (100mg) administered as 4-times daily i.v. infusions for a maximun of 15 days

Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]

Control Arm

NO INTERVENTION

Standard of care

Interventions

Anakinra 149 MG/ML Prefilled Syringe [Kineret] DRUG

Anakinra (100 mg/ 6 hours) i.v infusión during 15 days

Anakinra Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years.
• Severe pneumonia COVID-19 defined as:
• Nasopharyngeal smear with RCP positive for SARS-CoV-2
• X-Rays (or other technique) pulmonary infiltrates compatible with pneumonia.
• or more of the following criteria:
• Ambient air oxygen saturation \<= 94% measured with a pulse oximeter.
• Pa:FiO2 (partial pressure O2/fraction of inspired O2) \<=300.
• Sa:FiO2 (O2 saturation measured with pulse oximeter/ fraction of inspired O2) \<=350.
• High suspicion of CSS that could resemble MAS-like: represented by IL-6 values \> 40 pg/mL and/or ferritin \>500 ug/L and/or PCR \> 30 mg/L (rationale: ≥ 5 upper normal limit) and/or LDH \>300 UI/L. We have chosen these parameters because they are implemented in all the participating hospitals, they are a reflection of the cytokine storm and they have also been significant in terms of predicting mortality in patients with COVID-19 (9).
• Written informed consent. The protocol will be explained to the patient in front of a nurse who will act as a legal witness by signing the document on behalf of the patient.

You may not qualify if:

• Need for oro-tracheal intubation and/or invasive mechanical ventilation at the start of the study.
• AST/ALT with values greater than 5 times normal levels.
• Neutrophils \< 1.500 cell/mmc.
• Platelets \< 50.000 cell/mmc.
• Sepsis or pneumonia documented by other pathogens than SARS-CoV-2.
• Inability to obtain informed consent.
• Positivity for HBV, HCV or tuberculin test serology.
• Pregnancy.
• Use of other previous or concomitant biological treatments. Patients in concomitant treatment with other biologicals that may interfere will be excluded: tocilizumab, canakinumab, TNFalfa inhibitors, JAKiinibs
• Severe renal dysfunction (estimated glomerular filtration rate ≤ 30 ml / min / 1.73 m2) or receive continuous renal replacement therapy, hemodialysis or peritoneal dialysis.
• Uncontrolled hypertension (sitting systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg).
• Administration of plasma from convalescent patients who have recovered from SARS-CoV-2 infection.
• History of hypersensitivity or allergy to any component of the study drug.
• Predictable inability to cooperate with given instructions or study procedures.

Sponsors & Collaborators

• Fundacion Miguel Servet: lead

Study Sites (12)

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

Hospital Clinic

Barcelona, Catalonia, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, Catalonia, Spain

Location

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, Galicia, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Mallorca, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario de Cabueñes

Gijón, Principality of Asturias, 33394, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Related Publications (1)

• Fanlo P, Gracia-Tello BDC, Fonseca Aizpuru E, Alvarez-Troncoso J, Gonzalez A, Prieto-Gonzalez S, Freire M, Argibay AB, Pallares L, Todoli JA, Perez M, Bujan-Rivas S, Ibanez B; GEAS-SEMI Group. Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19: A Randomized Phase 2/3 Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237243. doi: 10.1001/jamanetworkopen.2023.7243.

  PMID: 37027155 DERIVED

MeSH Terms

Conditions

Pneumonia

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Patricia Fanlo Mateo, PhD

  Complejo Hospitalario de Navarra

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A phase 2/3, randomized, open label, parallel group, 2-arm, multicenter study investigating the efficacy and safety of intravenous administrations of the study drug,

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 23, 2020
• Study Start: May 8, 2020
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12)