Infection with SARS-COV-2 (=COVID-19) MedDRA version: 21.1 Level: PT Classification code 10035737 Term: Pneumonia viral System Organ Class: 10021881 - Infections and infestations MedDRA version: 21.1 Level: LLT Classification code 10003083 Term: ARDS System Organ Class: 100000004855 MedDRA version: 20.0 Level: LLT Classification code 10038700 Term: Respiratory infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 23.0 Level: PT Classification code 10084268 Term
Conditions
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Laboratory confirmed (i.e. PCR-based assay) infection with SARS-CoV-2 (ideally but not necessarily =72 hours before randomization for “antiviral” treatments) OR radiological signs of COVID-19 in chest X-ray or computed tomography* • Hospitalisation due to SARS-CoV-2 infection (for anti-viral treatment arms) • Requirement of oxygen support (due to oxygen saturation 3% drop in case of chronic obstructive lung disease) • Informed Consent obtained, the patient understands and agrees to comply with the planned study procedures, except for sub-study C: obtaining informed consent may be impossible due to the severe condition of the patient and may be waived • =18 years of age • For female patients with childbearing potential: willingness to perform effective measures of contraception during the study. • For treatment arm 4 (Convalescent plasma) only immunocompromised patients (e.g. after having received chemotherapy, with inherited or acquired immunodeficiency syndromes) are eligible • Sub-study A: eGFR of >20 mL/min • Sub-study B: outpatients with COVID-19 may be included • Sub-study B: blood pressure =130/85mmHg in 2 consecutive measurements OR patients with established and treated hypertension • Sub-study B: Control group 1: Patients with suspicion of but negative tests for COVID-19. This group may consist of hospitalized and non-hospitalized patients. • Sub-study B: control group 2: healthy volunteers • Sub-study C: Signs of respiratory deterioration and progressing inflammation: need for oxygen supplementation, non-invasive ventilation, high-flow oxygen devices or mechanical ventilation AND CRP levels >5mg/dL (for Pentaglobin only), and admission to an ICU (for Pentaglobin only). • Qualitative Study: all participants who are fluent in German or English will be asked about participation in this study part – which is however, optional If for any given reason a patient does not qualify to participate in the main study, this will not preclude participation in sub-study C. *In case of negative PCR but clear radiological signs of COVID-19 patients have to be retested with serial nasopharyngeal swabs and PCR and, if possible antibody based assays. In any case, a laboratory based proof of COVID-19 is required or else the subject may be excluded from the per protocol analysis. 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 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250
Exclusion criteria
Exclusion criteria: • Moribund or estimated life expectancy 5 times upper limit of normal) • Stage 4 chronic kidney disease or requiring dialysis for direct anticoagulant treatment • Allergy or intolerances to any of the experimental substances -> exclusion for the respective treatment arm; for asunercept known hereditary fructose intolerance • Anticipated discharge of hospital within 48 hours (for anti-viral treatment arms) • Contraindications treatment arm 2 (lopinavir/ritonavir): severe hepatic impairment, CYP3A4/5 metabolized drugs as deemed relevant by treating physicians, HIV positive • Contraindication treatment arm 3 (remdesivir): Bodyweight <40kg, • Contraindications treatment arm 5 (convalescent plasma): IgA deficiency • Sub-study A Contraindications: active bleeding or bleeding diathesis, lesion or condition considered as major risk factor for bleeding, recent brain or spinal injury, recent brain or spinal or ophthalmic surgery, recent intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms, major intraspinal or intracerebral vascular abnormalities. • Sub-study A: ongoing therapeutic anticoagulation, which will continue, according to clinical practice • Sub-study B Contraindications chronic heart failure, allergies, hypersensitivities and intolerances, severe hepatic impairment and/or cholestasis, concomitant therapy with aliskiren-containing medications (for patients with diabetes mellitus or a GFR<60ml/min/1.73m2), known significant bilateral renal artery stenosis or renal artery stenosis of a solitary kidney • Sub-study B: Control group 1: with or without RAS blockers, Control group 2: Healthy volunteers: concomitant medication with RAS-blockers • Sub-study C: known active HIV or viral hepatitis • Asunercept: females of childbearing potential • Sub-Study C: Known active tuberculosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of various experimental therapeutics for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); for efficacy assessment an ordinal scale for clinical severity assessment as proposed by the World Health Organization will be used: • Time to sustained improvement of one category from admission;Secondary Objective: • Time to discharge or to a NEWS of =2 and maintained for 24 hours, whichever occurs first • Change from baseline • Oxygenation free days until day 29 • Incidence and duration of new oxygen use during trial • Ventilator free days until day 29 • Incidence and duration of new mechanical ventilation use • Viral load/viral clearance change at baseline and 3x/w ? Duration of hospitalization, ICU treatments & admissions • 15-, 29- & 60-day mortality • Qualitative Study: semi-structured interviews • Renin-Angiotensin System (RAS)-fingerprint at baseline and at least once weekly • Within all patients, the impact of obesity and associated disesaes on mortality will be investigated • Cumulative incidence of serious adverse events • iscontinuation or temporary suspension of therapy • Changes in WBC,hemoglobin,platelets,creatinine,glucose,total bilirubin,ALT,AST • Within all patients, the impact of obesity and associated diseases on mortality;Primary end point(s): Time to sustained improvement of one category from admission in the 7-point clinical performance scale;Timepoint(s) of evaluation of this end point: measured daily until day 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Clinical Status of patients according to the above-mentioned WHO scale: ? Time to improvement of one category from admission ? Clinical status daily ? Mean change in the ranking on an ordinal scale from baseline • National Early Warning Score (NEWS): ? Time to discharge or to a NEWS of =2 and maintained for 24 hours, whichever occurs first ? Change from baseline • Oxygenation ? Oxygenation free days until day 29 ? Incidence and duration of new oxygen use during the trial (e.g. oxygen insufflation, high-flow oxygen, non-invasive ventilation, mechanical ventilation, etc.) • Mechanical Ventilation ? Ventilator free days until day 29 ? Incidence and duration of new mechanical ventilation use during the trial • Viral load/viral clearance ? Baseline, and three times a week until infection has resolved • Hospitalization ? Duration of hospitalization • Mortality ? 15-day, 29-day, 60-day mortality - Sub-Study A: number of thromboembolic events • Within all patients, the impact of obesity and associated disesaes on mortality will be investigated (e.g. mortality, inflammatory response, duration of hospitalization, intensive care unit admission, new oxygen use, duration of oxygen) - Exploratory assessment of transaminases (including alkaline phosphatase, gamma-glutamyltransferases (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT)) and liver function parameters (including bilirubin, prothrombin time, international normalized ratio, albumin, fibrinogen) and their course during the disease and treatment - An exploratory endpoint will encompass a comprehensive assessment of inflammatory parameters and their changes during treatment and wash out time, as well as exploratory genotype and RNA analysis with a focus on inflammation, coagulation, and the specific pathophysiology of the disease (if possible for center). - Sub-study C: modified SOFA score, paO2/FiO2 ratio, or SpO2/FiO2 ratio - Sub-study B: To investigate the RAS fin | — |
Countries
Austria
Contacts
Public ContactSponsor
Medical University of Vienna, Department of Clinical Pharmacology
Outcome results
None listed