Official Title
A Multicenter, Randomized, Active Controlled, Open Label, Platform Trial on the Efficacy and Safety of Experimental Therapeutics for Patients With COVID-19 (Caused by Infection With Severe Acute Respiratory Syndrome Coronavirus-2)
Brief Summary

The Austrian Coronavirus Adaptive Clinical Trial (ACOVACT) is a randomized, controlled, multicenter, open-label basket trial that aims to compare various antiviral treatments for COVID-19. Moreover three substudies have been integrated. Currently, patients will be randomized to receive (hydroxy-)chloroquine (Treatment stopped after reports of safety issues), lopinavir/ritonavir, remdesivir or standard of care. Moreover, these patients are eligible for substudy A (randomized to rivaroxaban 5mg 1-0-1 vs. standard of care), substudy B (renin-angiotensin (RAS) blockade vs. no RAS blockade for patients with blood pressure >120/80mmHg), and substudy C (asunercept vs standard of care, pentglobin vs. standard of care for patients with respiratory deterioration and high inflammatory biomarkers). Endpoints were chosen based on the master protocol published by the World Health Organisation and include a 7-point scale of clinical performance, mortality, oxygen requirement (both dose and type), duration of hospitalization, viral load and safety.

Unknown status
COVID-19

Drug: Chloroquine or Hydroxychloroquine

Hydroxychloroquine 200mg 2-0-2 on day 1 followed by 200mg 1-0-1, or Chloroquine 250mg 2-0-2, as available

Drug: Lopinavir/Ritonavir

Lopinavir/Ritonavir 200mg/50mg 2-0-2

Other: Best standard of care

best standard of care

Drug: Rivaroxaban

2.5mg 2-0-2 or 10mg 1/2-0-1/2, as applicable

Drug: Thromboprophylaxis

as local standard, most likely to be low molecular weight heparin

Drug: Candesartan

starting dose 4mg once daily, titrated to normotension

Drug: non-RAS blocking antihypertensives

This excludes angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (AT-blockers, sartans) and includes alpha-receptor antagonists, calcium antagonists, amongst others

Drug: Remdesivir

200mg on day 1, thereafter 100mg for a total of 5-10 treatment days, according to local standards

Drug: Asunercept 400mg

asunercept 400mg once per week, up to 4 doses in total

Drug: Asunercept 100mg

asunercept 100mg once per week, up to 4 doses in total

Drug: Asunercept 25mg

asunercept 25mg once per week, up to 4 doses in total

Drug: Pentaglobin

7ml/kg/day for 12h for 5 days

Eligibility 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, except for sub-study B, which may also
include outpatients with COVID-19

- 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

- Sub-study A: not on chronic anticoagulation Sub-study B: 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: 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 ICU admission
(for Pentaglobin only)

- For female patients with childbearing potential: willingness to perform effective
measures of contraception during the study

Exclusion Criteria

- 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 experimental substance (ineligibility for treatment arm),
for Asunercept known hereditary fructose intolerance

- Anticipated discharge from hospital within 48 hours (for any given reason)

- Contraindications for treatment arm 2 (lopinavir/ritonavir): severe hepatic
impairment, CYP3A4/5 metabolized drugs, as deemed relevant by treating physicians

- Contraindications for treatment arm 3 (remdesivir): <40kg bodyweight

- Known active HIV or viral hepatitis

- Substudy A contraindications for rivaroxaban: 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, ongoing
therapeutic anticoagulation, which will be continued, according to clinical practice

- Sub-study B contraindications for nitrendipine: chronic heart failure, allergies,
hypersensitivities and intolerances, severe hepatic impairment and/or cholestasis,
concomitant therapy with aliskirencontaining 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 C contraindications for IL-6 blockade: Contraindications: allergies and
intolerances, active untreated diverticulitis, inflammatory bowel disease, any
treatment with an IL-6 or IL-6R blocking drug (e.g. tocilizumab, sarilumab,
siltuximab) <30 days before study inclusion.

- Sub-study C: Known active tuberculosis.

- Asunercept: females of childbearing potential

- Sub-study C with Pentaglobin: Contraindications to Pentaglobin

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 99 Years
Countries
Austria
Locations

Medical University of Innsbruck
Innsbruck, Tirol, Austria

Medical University of Graz
Graz, Austria

Kepler University Hospital
Linz, Austria

Medical University of Vienna
Vienna, Austria

Wilhelminenspital
Vienna, Austria

SMZ Süd Kaiser Franz Josef Spital
Vienna, Austria

KH Hietzing
Vienna, Austria

SMZ Baumgartner Höhe Otto Wagner Spital
Vienna, Austria

SMZ Ost Donauspital
Vienna, Austria

Contacts

Bernd Jilma, MD
+4314040029810
klin-pharmakologie@meduniwien.ac.at

Christian Schörgenhofer, MD, PHD
+4314040029810
klin-pharmakologie@meduniwien.ac.at

Bernd Jilma, MD, Principal Investigator
Medical University of Vienna

Medical University of Vienna
NCT Number
MeSH Terms
COVID-19
Ritonavir
Lopinavir
Hydroxychloroquine
Chloroquine
Remdesivir
Candesartan
Antihypertensive Agents
Rivaroxaban