CLINICAL TRIAL OF THE USE OF ANAKINRA (ANTI IL-1) IN CYTOKINE STORM SYNDROME (CSS) SECONDARY TO COVID-19
- Conditions
- Hyperinflammation and respiratory distress in patients with SARS- CoV-2Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2020-001825-29-ES
- Lead Sponsor
- AVARRABIOMED - FUNDACIÓN MIGUEL SERVET
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 180
? Age 18-80 years.
? Severe pneumonia COVID-19 defined as:
o Nasopharyngeal smear with RCP positive for SARS-CoV-2
o X-Rays (or other technique) pulmonary infiltrates compatible with pneumonia.
o 1 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
? 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 < 1500 cell/mmc.
? Platelets < 50.000 cell/mmc.
? Sepsis or pneumonia documented by other pathogens than SARS-CoV-2.
? Existence of any life-threatening comorbidity or any other medical condition that, in the investigator's opinion, makes the patient unsuitable for inclusion.
? 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.
? Enrollment in another concurrent intervention clinical trial, or intake of an investigational medication within three months or 5 half-lives prior to inclusion in this study, if deemed to interfere with the objectives of this study as assessed by the investigator.
? Predictable inability to cooperate with given instructions or study procedures.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: To assess the effect of anakinra in addition to standard treatment on mortality in patients with severe COVID-19 and CSS pneumonia.;Primary end point(s): Treatment success, defined as number of patients not requiring mechanical ventilation by Day 15.<br>Number of patients not requiring mechanical ventilation (day 28).? Time to mechanical ventilation (days)<br>? Time to oxygen saturation normalization<br>? Stay in ICU and hospitalization (days);Timepoint(s) of evaluation of this end point: 15 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ? Total mortality rate (day 28)<br>? Mortality 48 hours, 7 days, in ICU and hospital<br>? Viral clearance / viral shedding<br>? Frequency and severity of AEs:<br>o Treatment-emergent severe fatal and life-threatening serious adverse events (SAEs).<br>o Adverse events leading to premature discontinuation of study treatment.<br>o Anaphylactic/anaphylactoid reactions.<br>o Anakinra treatment group: Severe neutropenia.<br>o Treatment-emergent laboratory abnormalities.;Timepoint(s) of evaluation of this end point: 28 days