Covid-19: A randomized, open-label, adaptive, proof-of- concept clinical trial of new antiviral drug candidates against SARS-CoV-2.

Covid-19: A randomized, open-label, adaptive, proof-of- concept clinical trial of new antiviral drug candidates against SARS-CoV-2. - Antivirals for COVID-19 DAWN AZITHRO

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-001614-38-BE

Enrollment

282

Registered

2020-04-06

Start date

2020-04-22

Completion date

Unknown

Last updated

2022-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19 MedDRA version: 20.0 Level: LLT Classification code 10038700 Term: Respiratory infection System Organ Class: 100000004862

Interventions

Trade Name: azithromycine Pharmaceutical Form: Tablet INN or Proposed INN: AZITHROMYCIN DIHYDRATE CAS Number: 117772-70-0 Trade Name: azithromycine Pharmaceutical Form: Tablet INN or Proposed INN: AZ

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Subject (=18 years old) or legally authorized representative provides informed consent prior to initiation of any study procedures. When signed informed consent is not possible (e.g. due to restrictions to prevent viral transmission), verbal informed consent in the presence of a witness not related to the investigational research study will be obtained. 2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures. 3. Male or non-pregnant female adult =18 years of age at time of enrolment. 4. Has a confirmed diagnosis of SARS-CoV-2 infection within 72 hours prior to randomization, defined as either: a. laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen or b. The combination of upper or lower respiratory infection symptoms (fever, cough, dyspnea, desaturation) and typical findings on chest CT scan and absence of other plausible diagnoses 5. Illness of any duration, and at least one of the following: a. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or b. Clinical assessment (evidence of rales/crackles on exam) AND SpO2 = 94% on room air, or c. Requiring mechanical ventilation and/or supplemental oxygen. 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 141 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 141

Exclusion criteria

Exclusion criteria: 1. ALT/AST > 5 times the upper limit of normal. 2. Pregnancy or breast feeding. 3. Allergy to any study medication 4. Any medical condition which would impose an unacceptable safety hazard by participation to the study. 5. Study drug specific exclusion criteria: *for Azithromycin : o heart failure with severely reduced ejection fraction (30%) o known prolonged long QT interval on ECG (> 470 msec males and > 480 females with Fridericia criteria; for patients with ventricular conduction delay the use of Rautaharju formula is also allowed ) o patients on Macrolides during the last week before admission *For other treatment strata, see arm-specific protocols.

Design outcomes

Primary

Measure	Time frame
Main Objective: The overall objective of the study is to evaluate the clinical efficacy and safety of Azithromycine relative to the standard of care in patients hospitalized with COVID-19.;Secondary Objective: To evaluate clinical efficacy of Azithromycine as compared to the control arm as assessed by Clinical Severity, Oxygenation, Mechanical Ventilation, Hospitalisation, Mortality and Evaluate the safety of the intervention through 28 days of follow-up as compared to the control arm as assessed by o Cumulative incidence of serious adverse events (SAEs) and adverse events (AEs) graded as grade 4 or 5. o Discontinuation or temporary suspension of drug administration (for any reason). o Changes in white cell count, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, and AST over time. ;Primary end point(s): Clinical status of subject at day 15 (on a 7-point ordinal scale): 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. Primary outcome will be time from Day 0 to sustained clinical improvement or life discharge, whichever comes first, whereby a sustained clinical improvement is defined as an improvement of = 2 points vs the highest value of Day 0 and 1 and sustained for at least 3 days.;Timepoint(s) of evaluation of this end point: Day 15	—

Measure

Time frame

Main Objective: The overall objective of the study is to evaluate the clinical efficacy and safety of Azithromycine relative to the standard of care in patients hospitalized with COVID-19.;Secondary Objective: To evaluate clinical efficacy of Azithromycine as compared to the control arm as assessed by Clinical Severity, Oxygenation, Mechanical Ventilation, Hospitalisation, Mortality and Evaluate the safety of the intervention through 28 days of follow-up as compared to the control arm as assessed by o Cumulative incidence of serious adverse events (SAEs) and adverse events (AEs) graded as grade 4 or 5. o Discontinuation or temporary suspension of drug administration (for any reason). o Changes in white cell count, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, and AST over time. ;Primary end point(s): Clinical status of subject at day 15 (on a 7-point ordinal scale): 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. Primary outcome will be time from Day 0 to sustained clinical improvement or life discharge, whichever comes first, whereby a sustained clinical improvement is defined as an improvement of = 2 points vs the highest value of Day 0 and 1 and sustained for at least 3 days.;Timepoint(s) of evaluation of this end point: Day 15

—

Secondary

Measure	Time frame
Secondary end point(s): SECONDARY END POINTS • • Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29. • Cumulative clinical status up to Day 15, i.e. sum of daily clinical status scores from Day 1 to 15. • Time to events (ICU, death, discharge) • Mortality on day 15 and day 29, • Duration of supplemental oxygen. • Duration of mechanical ventilation. • Duration of hospitalization. • Duration of intensive care stay. • Date and cause of death (if applicable). • NEWS assessed daily while hospitalized and on days 15 and 29. • Adverse events graded as grade 4 or 5 or SAEs, SARs or SUSARs. • Lab values: CRP, white cell count, absolute neutrophil count, absolute lymphocyte count, absolute eosinophil count, haemoglobin, platelets, serumcreatinine, eGFR (CKD-EPI), hsTroponinT, glucose, potassium, total bilirubin, ALT, and AST on days 1; 3, 5, 8, 11, 15 and 29 (If measured according to clinical indication). • Combined cardiac endpoint (any of the following: hsTtroponinT levels >0.5ng/mL, ventricular arrhythmia requiring intervention, reanimation, sudden cardiac death) • Follow-up of absolute QTc and delta QTc interval between baseline ECG and follow-up ECG at day 2-3 of treatment intervention, or with continouos ECG monitoring on ICU EXPLORATORY LONG-TERM OUTCOMES • Qualitative and quantitative PCR for SARS-CoV-2 in (naopharyngeal) swab on day 6 (when feasible) • Patients will be invited 6-8 weeks post discharge at the respiratory clinic for lung functional, functional and radiological evaluation if possible o Spirometry with reversibility o Lung volumes and diffusing capacity o Low dose CT scan o Laboratory o 6 minutes walk (at physicians discretion) • An telephone call on D90 post admission for survival status ;Timepoint(s) of evaluation of this end point: days 1, 2, 3, 5, 8, 11, 15 and 29	—

Measure

Time frame

Secondary end point(s): SECONDARY END POINTS • • Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29. • Cumulative clinical status up to Day 15, i.e. sum of daily clinical status scores from Day 1 to 15. • Time to events (ICU, death, discharge) • Mortality on day 15 and day 29, • Duration of supplemental oxygen. • Duration of mechanical ventilation. • Duration of hospitalization. • Duration of intensive care stay. • Date and cause of death (if applicable). • NEWS assessed daily while hospitalized and on days 15 and 29. • Adverse events graded as grade 4 or 5 or SAEs, SARs or SUSARs. • Lab values: CRP, white cell count, absolute neutrophil count, absolute lymphocyte count, absolute eosinophil count, haemoglobin, platelets, serumcreatinine, eGFR (CKD-EPI), hsTroponinT, glucose, potassium, total bilirubin, ALT, and AST on days 1; 3, 5, 8, 11, 15 and 29 (If measured according to clinical indication). • Combined cardiac endpoint (any of the following: hsTtroponinT levels >0.5ng/mL, ventricular arrhythmia requiring intervention, reanimation, sudden cardiac death) • Follow-up of absolute QTc and delta QTc interval between baseline ECG and follow-up ECG at day 2-3 of treatment intervention, or with continouos ECG monitoring on ICU EXPLORATORY LONG-TERM OUTCOMES • Qualitative and quantitative PCR for SARS-CoV-2 in (naopharyngeal) swab on day 6 (when feasible) • Patients will be invited 6-8 weeks post discharge at the respiratory clinic for lung functional, functional and radiological evaluation if possible o Spirometry with reversibility o Lung volumes and diffusing capacity o Low dose CT scan o Laboratory o 6 minutes walk (at physicians discretion) • An telephone call on D90 post admission for survival status ;Timepoint(s) of evaluation of this end point: days 1, 2, 3, 5, 8, 11, 15 and 29

—

Countries

Belgium

Contacts

Public Contactclinical trial center UZ Leuven

UZ Leuven

ctc@uzleuven.be

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026