Austrian CoronaVirus Adaptive Clinical Trial (COVID-19)

NCT04351724 | Unknown Phase 2

• 1 other identifier: ACOVACT
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 9

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• sustained improvement (>48h) of one point on the WHO Scale

  The primary endpoint is time to clinical improvement which is defined as time from randomization to an (sustained) improvement of at least one category on two consecutive days compared to the status at randomization measured on a seven-category ordinal scale (proposed by WHO). The 7-categories of the World Health Organization proposed scale, as follows: 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. During hospitalization this score will be determined daily (till day 29). If a patient is released from the hospital before day 29, the score will be determined at day 11 and 29 after randomization (depending when the patient was released or by telephone call).

  Inclusion to day 29, daily evaluation

Secondary Outcomes (28)

• Time to improvement on WHO Scale

  Inclusion to day 29, daily evaluation

• Mean change in the ranking on an ordinal scale from baseline

  Inclusion to day 29, daily evaluation

• time to discharge or a National Early Warning Score (NEWS) ≤2 (maintained for 24h), whichever occurs first

  Inclusion to day 29, daily evaluation

• change from baseline in National Early Warning Score (NEWS)

  Inclusion to day 29, daily evaluation

• Oxygenation free days

  Inclusion to day 29, daily evaluation

Study Arms (14)

(Hydroxy)Chloroquine (STOPPED)

EXPERIMENTAL

Due to limited availability of the experimental substances, this arm will include both chloroquine and hydroxychloroquine treatment. However, both substances are similar chemically and also with regards to the mechanism of action comparable. Dosage: Hydroxychloroquine 200mg 2-0-2 on day 1 followed by 200mg 1-0-1, or Chloroquine 250mg 2-0-2, as available

Drug: Chloroquine or Hydroxychloroquine

Lopinavir/Ritonavir

EXPERIMENTAL

Dosage: 200mg/50mg 4-0-4 on day 1 and 3-0-3 thereafter

Drug: Lopinavir/Ritonavir

Standard of Care

OTHER

patients will be treated with "standard of care", which precludes treatment with lopinavir/ritonavir or (hydroxy-)chloroquine

Other: Best standard of care

Rivaroxaban

EXPERIMENTAL

5mg 1-0-1

Drug: Rivaroxaban

Thromboprophylaxis

ACTIVE COMPARATOR

according to local standard

Drug: Thromboprophylaxis

RAS Blockade

EXPERIMENTAL

Renin-Angiotensin-System-Blockade (RAS) by candesartan intake starting with 4mg once daily and titrated to normotension patients \> 120/80 mmHG are eligible

Drug: Candesartan

non-RAS-Blockade

ACTIVE COMPARATOR

non-RAS blocking antihypertensive agents titrated to normotension Those with normal blood pressure may only be controlled without further treatment

Drug: non-RAS blocking antihypertensives

Asunercept 25mg

EXPERIMENTAL

25mg 1x per week, maximum of four doses only patients with oxygen requirement

Drug: Asunercept 25mg

Asunercept 100mg

EXPERIMENTAL

100mg 1x per week, maximum of four doses only patients with oxygen requirement

Drug: Asunercept 100mg

Asunercept 400mg

EXPERIMENTAL

400mg 1x per week, maximum of four doses only patients with oxygen requirement

Drug: Asunercept 400mg

Best Standard of Care - Control Group for Asunercept

OTHER

only patients with oxygen requirement

Other: Best standard of care

Remdesivir

EXPERIMENTAL

200mg loading dose on day 1, 100mg for a total treatment duration of 5-10 days

Drug: Remdesivir

Pentaglobin

EXPERIMENTAL

Patients treated at the intensive care unit only, continuous infusion of 7ml/kg/day over 12h for 5 days

Drug: Pentaglobin

best standard of care

OTHER

Patients treated at the intensive care unit only

Other: Best standard of care

Interventions

Chloroquine or Hydroxychloroquine DRUG

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

(Hydroxy)Chloroquine (STOPPED)

Lopinavir/Ritonavir DRUG

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

Lopinavir/Ritonavir

Best standard of care OTHER

best standard of care

Best Standard of Care - Control Group for Asunercept; Standard of Care; best standard of care

Rivaroxaban DRUG

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

Rivaroxaban

Thromboprophylaxis DRUG

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

Thromboprophylaxis

Candesartan DRUG

starting dose 4mg once daily, titrated to normotension

RAS Blockade

non-RAS blocking antihypertensives DRUG

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

non-RAS-Blockade

Remdesivir DRUG

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

Remdesivir

Asunercept 400mg DRUG

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

Asunercept 400mg

Asunercept 100mg DRUG

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

Asunercept 100mg

Asunercept 25mg DRUG

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

Asunercept 25mg

Pentaglobin DRUG

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

Pentaglobin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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: Known active tuberculosis.
• Asunercept: females of childbearing potential
• Sub-study C with Pentaglobin: Contraindications to Pentaglobin

Sponsors & Collaborators

• Medical University of Vienna: lead
• Kaiser Franz Josef Hospital: collaborator
• SMZ-Ost Donauspital: collaborator
• Otto Wagner Hospital: collaborator
• Hospital Hietzing: collaborator
• Wilhelminenspital Vienna: collaborator
• Medical University Innsbruck: collaborator
• Medical University of Graz: collaborator
• Kepler University Hospital: collaborator

Study Sites (9)

Medical University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

NOT YET RECRUITING

Medical University of Graz

Graz, Austria

RECRUITING

Kepler University Hospital

Linz, Austria

RECRUITING

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Wilhelminenspital

Vienna, 1090, Austria

NOT YET RECRUITING

SMZ Süd Kaiser Franz Josef Spital

Vienna, 1100, Austria

RECRUITING

KH Hietzing

Vienna, 1130, Austria

NOT YET RECRUITING

SMZ Baumgartner Höhe Otto Wagner Spital

Vienna, 1140, Austria

NOT YET RECRUITING

SMZ Ost Donauspital

Vienna, 1220, Austria

NOT YET RECRUITING

Related Publications (5)

• Gleiss A. Visualizing a marker's degrees of necessity and of sufficiency in the predictiveness curve. BMC Med Res Methodol. 2025 Apr 23;25(1):107. doi: 10.1186/s12874-025-02544-y.

  PMID: 40269760 DERIVED

• Hofstetter L, Tinhof V, Mayfurth H, Kurnikowski A, Rathkolb V, Reindl-Schwaighofer R, Traugott M, Omid S, Zoufaly A, Tong A, Kropiunigg U, Hecking M. Experiences and challenges faced by patients with COVID-19 who were hospitalised and participated in a randomised controlled trial: a qualitative study. BMJ Open. 2022 Oct 11;12(10):e062176. doi: 10.1136/bmjopen-2022-062176.

  PMID: 36220325 DERIVED

• Karolyi M, Pawelka E, Omid S, Koenig F, Kauer V, Rumpf B, Hoepler W, Kuran A, Laferl H, Seitz T, Traugott M, Rathkolb V, Mueller M, Abrahamowicz A, Schoergenhofer C, Hecking M, Assinger A, Wenisch C, Zeitlinger M, Jilma B, Zoufaly A. Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT). Front Pharmacol. 2022 Jul 22;13:870493. doi: 10.3389/fphar.2022.870493. eCollection 2022.

  PMID: 35935856 DERIVED

• Heber S, Pereyra D, Schrottmaier WC, Kammerer K, Santol J, Rumpf B, Pawelka E, Hanna M, Scholz A, Liu M, Hell A, Heiplik K, Lickefett B, Havervall S, Traugott MT, Neubock MJ, Schorgenhofer C, Seitz T, Firbas C, Karolyi M, Weiss G, Jilma B, Thalin C, Bellmann-Weiler R, Salzer HJF, Szepannek G, Fischer MJM, Zoufaly A, Gleiss A, Assinger A. A Model Predicting Mortality of Hospitalized Covid-19 Patients Four Days After Admission: Development, Internal and Temporal-External Validation. Front Cell Infect Microbiol. 2022 Jan 24;11:795026. doi: 10.3389/fcimb.2021.795026. eCollection 2021.

  PMID: 35141170 DERIVED

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Chloroquine; Hydroxychloroquine; Lopinavir; Rivaroxaban; candesartan; remdesivir; pentaglobulin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines

Study Officials

• Bernd Jilma, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bernd Jilma, MD

CONTACT

+4314040029810; klin-pharmakologie@meduniwien.ac.at

Christian Schörgenhofer, MD, PHD

CONTACT

+4314040029810; klin-pharmakologie@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.Prof.Dr. Bernd Jilma

Model Details: Three main study arms (antiviral treatments) and three substudies (A, B, C) are planned. The main study arms are exclusive, while patients from the main study arms may participate in one or more substudies.

Study Record Dates

• First Submitted: April 10, 2020
• First Posted: April 17, 2020
• Study Start: April 16, 2020
• Primary Completion: December 1, 2021
• Study Completion: March 31, 2022
• Last Updated: March 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (9)