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COVID-19Phase 2/3ACOVACTNCT04351724

Austrian CoronaVirus Adaptive Clinical Trial (COVID-19)

A Phase 2/3 study testing Chloroquine or Hydroxychloroquine, Lopinavir/Ritonavir and Rivaroxaban in people with COVID-19, run by Medical University of Vienna at 9 sites in Austria.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 yearsHealthy volunteers can take part
Conditions the study is for
COVID-19
What is being tested?
Chloroquine or Hydroxychloroquine, Lopinavir/Ritonavir and Rivaroxaban
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
500 participants
Where
9 sitesAustria
Study dates
16 Apr 2020to 31 Mar 2022
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

9 sites in 1 country.

Bernd Jilma, MD contact

+4314040029810

klin-pharmakologie@meduniwien.ac.at

Christian Schörgenhofer, MD, PHD contact

+4314040029810

klin-pharmakologie@meduniwien.ac.at

9 sites in 1 country

Austria9 sites, 9 recruiting

  • Medical University of Graz

    Graz

    Robert Krause, Prof.Dr., +43 316 385 81796, robert.krause@medunigraz.at

    Robert Krause, Prof.Dr.

    Recruiting

  • Medical University of Innsbruck

    Innsbruck, Tyrol, 6020

    Günter Weiss, MD, +4351250423251, guenter.weiss@i-med.ac.at

    Not yet recruiting

  • Kepler University Hospital

    Linz

    Bernd Lamprecht, MD, +43 (0)5 7680 83 - 6910, Bernd.Lamprecht@kepleruniklinikum.at

    Bernd Lamprecht, MD

    Recruiting

  • Medical University of Vienna

    Vienna, 1090

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

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

    Recruiting

  • Wilhelminenspital

    Vienna, 1090

    Georg-Christian Funk, MD, +431491502201, georg-christian.funk@wienkav.at

    Not yet recruiting

  • SMZ Süd Kaiser Franz Josef Spital

    Vienna, 1100

    Alexander Zoufaly, MD, 431601912408, alexander.zoufaly@wienkav.at

    Recruiting

  • KH Hietzing

    Vienna, 1130

    Kurt Redlich, MD, +431801103173, kurt.redlich@wienkav.at

    Not yet recruiting

  • SMZ Baumgartner Höhe Otto Wagner Spital

    Vienna, 1140

    Brigitte Schmied, MD, +4319106042713, brigitte.schmied@meduniwien.ac.at

    Not yet recruiting

  • SMZ Ost Donauspital

    Vienna, 1220

    Thomas Stefenelli, MD, +431288023102, thomas.stefenelli@wienkav.at

    Not yet recruiting

Other trials in Austria

About this study

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)

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
Being tested
Chloroquine or Hydroxychloroquine, Lopinavir/Ritonavir, Best standard of care, Rivaroxaban, Thromboprophylaxis
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Chloroquine or HydroxychloroquineDrug

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

  • Lopinavir/RitonavirDrug

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

  • Best standard of careOther

    best standard of care

  • RivaroxabanDrug

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

  • ThromboprophylaxisDrug

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

  • CandesartanDrug

    starting dose 4mg once daily, titrated to normotension

  • non-RAS blocking antihypertensivesDrug

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

  • RemdesivirDrug

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

  • Asunercept 400mgDrug

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

  • Asunercept 100mgDrug

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

  • Asunercept 25mgDrug

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

  • PentaglobinDrug

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

Study groups in NCT04351724
Study groupRoleWhat they receive
(Hydroxy)Chloroquine (STOPPED)ExperimentalDue 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
Receives: Drug: Chloroquine or Hydroxychloroquine
Lopinavir/RitonavirExperimentalDosage: 200mg/50mg 4-0-4 on day 1 and 3-0-3 thereafter
Receives: Drug: Lopinavir/Ritonavir
Standard of CareOtherpatients will be treated with "standard of care", which precludes treatment with lopinavir/ritonavir or (hydroxy-)chloroquine
Receives: Other: Best standard of care
RivaroxabanExperimental5mg 1-0-1
Receives: Drug: Rivaroxaban
ThromboprophylaxisActive comparatoraccording to local standard
Receives: Drug: Thromboprophylaxis
RAS BlockadeExperimentalRenin-Angiotensin-System-Blockade (RAS) by candesartan intake starting with 4mg once daily and titrated to normotension patients > 120/80 mmHG are eligible
Receives: Drug: Candesartan
non-RAS-BlockadeActive comparatornon-RAS blocking antihypertensive agents titrated to normotension Those with normal blood pressure may only be controlled without further treatment
Receives: Drug: non-RAS blocking antihypertensives
Asunercept 25mgExperimental25mg 1x per week, maximum of four doses only patients with oxygen requirement
Receives: Drug: Asunercept 25mg
Asunercept 100mgExperimental100mg 1x per week, maximum of four doses only patients with oxygen requirement
Receives: Drug: Asunercept 100mg
Asunercept 400mgExperimental400mg 1x per week, maximum of four doses only patients with oxygen requirement
Receives: Drug: Asunercept 400mg
Best Standard of Care - Control Group for AsunerceptOtheronly patients with oxygen requirement
Receives: Other: Best standard of care
RemdesivirExperimental200mg loading dose on day 1, 100mg for a total treatment duration of 5-10 days
Receives: Drug: Remdesivir
PentaglobinExperimentalPatients treated at the intensive care unit only, continuous infusion of 7ml/kg/day over 12h for 5 days
Receives: Drug: Pentaglobin
best standard of careOtherPatients treated at the intensive care unit only
Receives: Other: Best standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Inclusion to day 29, daily evaluation

Secondary outcomes (28)

  1. Time to improvement on WHO Scale

    The scale described in the primary endpoint is used

    Measured: Inclusion to day 29, daily evaluation

  2. Mean change in the ranking on an ordinal scale from baseline

    The scale described in the primary endpoint is used

    Measured: Inclusion to day 29, daily evaluation

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

    the National Early Warning Score includes respiratory rate, oxygen saturation, use of supplemental oxygen, temperature, systolic blood pressure, heart rate and levels of consciousness (AVPU Scale)

    Measured: Inclusion to day 29, daily evaluation

  4. change from baseline in National Early Warning Score (NEWS)

    The scale described in the primary endpoint is used

    Measured: Inclusion to day 29, daily evaluation

  5. Oxygenation free days

    Measured: Inclusion to day 29, daily evaluation

  6. Incidence of new oxygen use during the trial

    new oxygen may include insufflation or oxygen mask, high flow oxygen devices, non-invasive ventilation devices or mechanical ventilation

    Measured: Inclusion to day 29, daily evaluation

  7. duration of oxygen use during the trial

    Measured: Inclusion to day 29, daily evaluation

  8. Ventilator free days until day 29

    number of days with requirement of mechanical ventilation

    Measured: Inclusion to day 29, daily evaluation

  9. Incidence of new mechanical ventilation use during the trial

    Measured: Inclusion to day 29, daily evaluation

  10. duration of mechanical ventilation use during the trial

    Measured: Inclusion to day 29, daily evaluation

  11. Viral load/viral clearance

    obtained by polymerase chain reaction in nasal/oropharyngeal swabs, performed at baseline and then three times a week, if possible

    Measured: Inclusion to day 29, daily evaluation

  12. Duration of Hospitalization

    Measured: Inclusion to day 29, daily evaluation

  13. Mortality

    Measured: 15-day, 29-day, 60-day, 90-day mortality

  14. Obesity - mortality

    BMI (kg/m2), within all subjects the impact of obesity on overall mortality will be investigated

    Measured: BMI at admission, mortality until day 29

  15. Obesity - duration of hospitalization

    BMI (kg/m2) , within all subjects the impact of obesity on the duration of hospitalization will be investigated

    Measured: BMI at admission, duration of hospitalization until day 29 or discharge

  16. Obesity - ICU admission

    BMI (kg/m2) , within all subjects the impact of obesity on ICU admission will be investigated

    Measured: BMI at admission, ICU admission until day 29 or discharge

  17. Obesity - new oxygen use

    BMI (kg/m2) new oxygen may include insufflation or oxygen mask, high flow oxygen devices, non-invasive ventilation devices or mechanical ventilation

    Measured: BMI at admission, new oxygen use until day 29 or discharge

  18. Drug-drug interactions with lopinavir/ritonavir

    lopinavir and ritonavir both interact with numerous other drugs by inhibiting the cytochrome enzymes 3A4. Using commercially available drug-interaction programs, the number and severity grading of drug-drug-interactions will be documented (for instance uptodate interaction tool, medscape). This is an exploratory analysis of drug-drug interactions with the above mentioned substances. severity grading usually encompass "contraindicated", "serious", "monitor closely", "minor" interaction.

    Measured: Inclusion to day 29, daily evaluation

  19. Renin Angiotensin System (RAS) fingerprint

    for sub-study B only: RAS fingerprint measures metabolites involved in the renin-angiotensin-system. The influence of randomized treatment with candesartan (RAS blockade) will be analyzed

    Measured: Inclusion to day 29, daily evaluation

  20. SpO2/FiO2 ratio

    for sub-study C only

    Measured: Inclusion to day 29, daily evaluation

  21. paO/FiO2 ratio

    for sub-study C only, for ICU patients only

    Measured: Inclusion to day 29, daily evaluation

  22. modified Sequential Organ Failure Assessment

    for sub-study C only

    Measured: Inclusion to day 29, daily evaluation

  23. C-reactive protein

    unit mg/dL

    Measured: baseline, day 2, 3, 4, 5, 7

  24. Interleukin-6

    unit pg/mL

    Measured: baseline, day 2, 3, 4, 5, 7

  25. procalcitonin

    unit ng/mL

    Measured: baseline, day 2, 3, 4, 5, 7

  26. IgM Concentrations

    unit mg/dL

    Measured: baseline, day 2, 3, 4, 5, 7

  27. IgA Concentrations

    unit mg/dL

    Measured: baseline, day 2, 3, 4, 5, 7

  28. differential blood counts

    Measured: baseline, day 2, 3, 4, 5, 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2020
  2. Study start16 Apr 2020
  3. Primary completion1 Dec 2021 (estimated)
  4. Study completion31 Mar 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
500 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04351724
Sponsor's protocol ID
ACOVACT
Acronym
ACOVACT
Status last verified
Feb 2021
First submitted
10 Apr 2020
Last updated
2 Mar 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Anonymized and pseudonymized data will be published in peer reviewed journals and may be presented at congresses and conferences

Publications

  • 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.

    PubMed 40269760

  • 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.

    PubMed 36220325

  • 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.

    PubMed 35935856

  • 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.

    PubMed 35141170

  • 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.

    PubMed 34473343

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Chloroquine or Hydroxychloroquine, Lopinavir/Ritonavir and Rivaroxaban in people with COVID-19, run by Medical University of Vienna at 9 sites in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Bernd Jilma, MD (+4314040029810, klin-pharmakologie@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

sustained improvement (>48h) of one point on the WHO Scale (time frame: Inclusion to day 29, daily evaluation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04351724, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.

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