COVID-19 MedDRA version: 20.0 Level: LLT Classification code 10038700 Term: Respiratory infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Aprotinin
Pharmaceutical Form: Infusion
INN or Proposed INN: APROTININ
CAS Number: 9087-70-1
Other descriptive name: APROTININ
Product Name: Anakinra
Pharmaceutical Form: Infusion
INN o
Sponsors
UZLeuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject (=18 years old) or legally authorized representative provides informed consent prior to initiation of any study procedures. When signed informed consent is not possible (e.g. due to restrictions to prevent viral transmission), verbal informed consent in the presence of a witness will be obtained and documented in the medical files. Signed informed consent will be obtained as soon as the safety concerns are mitigated. 2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures. 3. Male or non-pregnant female adult =18 years of age at time of enrolment. 4. Has a confirmed diagnosis of SARS-CoV-2 infection, defined as either: a. laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen as diagnosed within 72 hours prior to randomization or b. The combination of upper or lower respiratory infection symptoms (fever, cough, dyspnea, desaturation) and typical findings on chest CT scan and absence of other plausible diagnoses 5. Illness of any duration, and at least one of the following: a. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or b. Clinical assessment (evidence of rales/crackles on lung auscultation) AND SpO2 = 94% on room air, or c. Requiring mechanical ventilation and/or supplemental oxygen. 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 105 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: 1. ALT/AST > 8 times the upper limit of normal. 2. Pregnancy or breastfeeding. 3. Allergy to any study medication. 4. Any medical condition which would impose an unacceptable safety hazard by participation in the study. 5. Study drug-specific exclusion criteria: • For Aprotinin: o Known active thromboembolic disease, defined as a history of idiopathic (unprovoked) deep vein thrombosis or pulmonary embolism, recent (180mmHg, or diastolic blood pressure >110mmHg) o Clinical suspicion of latent tuberculosis o Clinical suspicion of severe bacterial surinfection (e.g. ventilator-associated pneumonia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the clinical efficacy of different investigational therapeutics as compared to one another or the control arm as assessed by Clinical Severity, Oxygenation, Mechanical Ventilation, Hospitalisation, Host thrombo-inflammatory status, Mortality and Evaluate the safety of the interventions through 28 days of follow-up as compared to the control arm as assessed by o Cumulative incidence of serious adverse events (SAEs) and adverse events (AEs) graded as severe. o Discontinuation or temporary suspension of drug administration (for any reason). o Changes in white cell count, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, and AST over time.;Primary end point(s): Pilot phase of DAWN-ANTICO: D-dimer on day 6 Clinical status of subject at day 15 (on a 7-point ordinal scale): 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death. Primary outcome will be time from Day 0 to sustained clinical improvement or life discharge, whichever comes first, whereby a sustained clinical improvement is defined as an improvement of > 2 points vs the highest value of Day 0 and 1 and sustained for at least 3 days.;Timepoint(s) of evaluation of this end point: Day 6 and 15;Main Objective: The overall objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the standard of care in patients hospitalized with COVID-19. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Status on an ordinal scale assessed daily while hospitalized and on days 15 and 28. • Mortality on day 15 and day 28, time to death • Time to clinical improvement (n° days from hospitalization to first 2-point improvement from highest previously recorded clinical state on the 7-point ordinal scale) • Duration of supplemental oxygen. • Duration of mechanical ventilation, time to live weaning from ventilation. • Duration of hospitalization, time to live hospital discharge • Duration of intensive care stay, time to live discharge from ICU • Date and cause of death (if applicable). • Use and cumulative dosesdose of corticosteroidsrescue anti-inflammatory therapy • Adverse events graded as severe or SAEs, SARS, SUSARs. • Lab values: including but not limited to CRP, white cell count, absolute neutrophil count, absolute lymphocyte count, absolute eosinophil count, hemoglobin, platelets, serum creatinine, eGFR (CKD-EPI) and CrCl (Cockroft-Gault), hsTroponin T, glucose, potassium, total bilirubin, ALT, and AST on days 1; 3, 5, 8, 11, 15 and 28 (If measured according to clinical indication). • Markers of hyper-inflammation: (CRP, ferritin, LDH, interleukin profile) at baseline and on day 3, 6 and 15 • Markers of thrombotic activation and kallikrein-bradykinin activation: (D-dimers, fibrinogen, PT, aPTT, C1-inhibitor, factor XII) at baseline and on 3, 6 and 15 • Markers of adrenal function (Cortisol, ACTH, albumin/transcortin) at baseline and on day 3, 6 and 15 • Combined cardiac endpoint during hospitalization (any of the following: high sensitive troponin T levels >0.5ng/mL, ventricular arrhythmia requiring intervention, reanimation, sudden cardiac death) • Incidence of thrombotic events during hospitalization • Incidence of major bleeding complications during hospitalization as per ISTH criteria. ISTH major bleeding is defined as having a symptomatic presentation and o Fatal bleeding, and/or o Bleeding in a critical ar | — |
Countries
Belgium
Contacts
Public ContactCaroline Devooght
UZ Leuven
Outcome results
None listed