A multicenter, randomized, active controlled, open label, platform trial on the efficacy and safety of experimental therapeutics for patients with a lung disease caused by coronavirus infectionACOVACT (Austrian CoronaVirus Adaptive Clinical Trial)
- Conditions
- Infection with SARS-COV-2 (=COVID-19)MedDRA version: 21.1Level: PTClassification code 10035737Term: Pneumonia viralSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 21.1Level: LLTClassification code 10003083Term: ARDSSystem Organ Class: 100000004855MedDRA version: 20.0Level: LLTClassification code 10038700Term: Respiratory infectionSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 23.0Level: PTClassification code 10084268Term: COVID-19System Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2020-001302-30-AT
- Lead Sponsor
- Medical University of Vienna
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 500
•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 <94% on ambient air or >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
•Moribund or estimated life expectancy <1 month (e.g. terminal cancer, etc.)
•Patient does not qualify for intensive care, based on local triage criteria
•Pregnancy or breastfeeding
•Severe liver dysfunction (e.g. ALT/AST > 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method