Austrian CoronaVirus Adaptive Clinical Trial (COVID-19)
- Conditions
- COVID-19
- Interventions
- Other: Best standard of careDrug: non-RAS blocking antihypertensivesDrug: Thromboprophylaxis
- Registration Number
- NCT04351724
- Lead Sponsor
- Medical University of Vienna
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 500
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (Hydroxy)Chloroquine (STOPPED) Chloroquine or Hydroxychloroquine 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 Lopinavir/Ritonavir Lopinavir/Ritonavir Dosage: 200mg/50mg 4-0-4 on day 1 and 3-0-3 thereafter Standard of Care Best standard of care patients will be treated with "standard of care", which precludes treatment with lopinavir/ritonavir or (hydroxy-)chloroquine Asunercept 100mg Asunercept 100mg 100mg 1x per week, maximum of four doses only patients with oxygen requirement Asunercept 400mg Asunercept 400mg 400mg 1x per week, maximum of four doses only patients with oxygen requirement best standard of care Best standard of care Patients treated at the intensive care unit only non-RAS-Blockade non-RAS blocking antihypertensives non-RAS blocking antihypertensive agents titrated to normotension Those with normal blood pressure may only be controlled without further treatment Asunercept 25mg Asunercept 25mg 25mg 1x per week, maximum of four doses only patients with oxygen requirement Best Standard of Care - Control Group for Asunercept Best standard of care only patients with oxygen requirement Remdesivir Remdesivir 200mg loading dose on day 1, 100mg for a total treatment duration of 5-10 days Thromboprophylaxis Thromboprophylaxis according to local standard Rivaroxaban Rivaroxaban 5mg 1-0-1 RAS Blockade Candesartan Renin-Angiotensin-System-Blockade (RAS) by candesartan intake starting with 4mg once daily and titrated to normotension patients \> 120/80 mmHG are eligible Pentaglobin Pentaglobin Patients treated at the intensive care unit only, continuous infusion of 7ml/kg/day over 12h for 5 days
- Primary Outcome Measures
Name Time Method sustained improvement (>48h) of one point on the WHO Scale Inclusion to day 29, daily evaluation 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).
- Secondary Outcome Measures
Name Time Method Obesity - mortality BMI at admission, mortality until day 29 BMI (kg/m2), within all subjects the impact of obesity on overall mortality will be investigated
modified Sequential Organ Failure Assessment Inclusion to day 29, daily evaluation for sub-study C only
C-reactive protein baseline, day 2, 3, 4, 5, 7 unit mg/dL
Time to improvement on WHO Scale Inclusion to day 29, daily evaluation The scale described in the primary endpoint is used
Oxygenation free days Inclusion to day 29, daily evaluation Duration of Hospitalization Inclusion to day 29, daily evaluation Mortality 15-day, 29-day, 60-day, 90-day mortality Obesity - new oxygen use BMI at admission, new oxygen use until day 29 or discharge BMI (kg/m2) new oxygen may include insufflation or oxygen mask, high flow oxygen devices, non-invasive ventilation devices or mechanical ventilation
Renin Angiotensin System (RAS) fingerprint Inclusion to day 29, daily evaluation 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
time to discharge or a National Early Warning Score (NEWS) ≤2 (maintained for 24h), whichever occurs first Inclusion to day 29, daily evaluation 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)
change from baseline in National Early Warning Score (NEWS) Inclusion to day 29, daily evaluation The scale described in the primary endpoint is used
Incidence of new oxygen use during the trial Inclusion to day 29, daily evaluation new oxygen may include insufflation or oxygen mask, high flow oxygen devices, non-invasive ventilation devices or mechanical ventilation
Incidence of new mechanical ventilation use during the trial Inclusion to day 29, daily evaluation Drug-drug interactions with lopinavir/ritonavir Inclusion to day 29, daily evaluation 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.
paO/FiO2 ratio Inclusion to day 29, daily evaluation for sub-study C only, for ICU patients only
IgA Concentrations baseline, day 2, 3, 4, 5, 7 unit mg/dL
Mean change in the ranking on an ordinal scale from baseline Inclusion to day 29, daily evaluation The scale described in the primary endpoint is used
duration of oxygen use during the trial Inclusion to day 29, daily evaluation Ventilator free days until day 29 Inclusion to day 29, daily evaluation number of days with requirement of mechanical ventilation
Viral load/viral clearance Inclusion to day 29, daily evaluation obtained by polymerase chain reaction in nasal/oropharyngeal swabs, performed at baseline and then three times a week, if possible
IgM Concentrations baseline, day 2, 3, 4, 5, 7 unit mg/dL
differential blood counts baseline, day 2, 3, 4, 5, 7 duration of mechanical ventilation use during the trial Inclusion to day 29, daily evaluation Obesity - duration of hospitalization BMI at admission, duration of hospitalization until day 29 or discharge BMI (kg/m2) , within all subjects the impact of obesity on the duration of hospitalization will be investigated
Obesity - ICU admission BMI at admission, ICU admission until day 29 or discharge BMI (kg/m2) , within all subjects the impact of obesity on ICU admission will be investigated
SpO2/FiO2 ratio Inclusion to day 29, daily evaluation for sub-study C only
Interleukin-6 baseline, day 2, 3, 4, 5, 7 unit pg/mL
procalcitonin baseline, day 2, 3, 4, 5, 7 unit ng/mL
Trial Locations
- Locations (9)
Medical University of Innsbruck
🇦🇹Innsbruck, Tirol, Austria
Wilhelminenspital
🇦🇹Vienna, Austria
SMZ Ost Donauspital
🇦🇹Vienna, Austria
KH Hietzing
🇦🇹Vienna, Austria
Medical University of Graz
🇦🇹Graz, Austria
Medical University of Vienna
🇦🇹Vienna, Austria
SMZ Baumgartner Höhe Otto Wagner Spital
🇦🇹Vienna, Austria
Kepler University Hospital
🇦🇹Linz, Austria
SMZ Süd Kaiser Franz Josef Spital
🇦🇹Vienna, Austria