Recombinant human angotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 to block viral entry and decrease viral replication.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
185
Patients will be treated with APN01 intravenously twice daily (BID).
Patients will be treated with placebo intravenously twice daily (BID).
All Cause-death or Invasive Mechanical Ventilation
The primary endpoint was a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.
Time frame: 28 days
Lactate Dehydrogenase (LDH) Level
Log transformed levels of LDH at Day 5 as a surrogate marker for organ damage (powered secondary endpoint).
Time frame: Day 5
Mortality
28-day mortality (all cause-death).
Time frame: 28 days
Ventilator-free Days (VFD)
VFD up to 28 days or hospital discharge. VFD and mechanical-VFD (mVFD) were calculated as time in the study minus duration of ventilation and were set to zero if the duration of ventilation exceeded the time in the study. Three analysis approaches were used: 1) Death not censored: (m)VFD was set to zero for patients who died. 2) Death censored: patients who died before or on Day 28 were censored at the day before death. 3) Alive patients analyzed: only patients who were alive at Day 28, hospital discharge, or early termination were included in the analysis.
Time frame: 28 days
Time to Death
Time to death (all causes).
Time frame: 28 days
Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
The WHO Clinical Progression Scale provides a measure of illness severity across an 11 point range from 0 (not infected) to 10 (dead) as follows (scores 4-9 contain measures of respiratory failure): Uninfected, no viral deoxyribonucleic acid (DNA) detected = 0; Asymptomatic, viral DNA detected = 1; Symptomatic, independent = 2; Symptomatic, assistance needed = 3; Hospitalized, no oxygen therapy = 4; Hospitalized, oxygen by mask or nasal prongs = 5; Hospitalized, oxygen by non-invasive ventilation (NIV) or high flow = 6; Intubation and mechanical ventilation, partial pressure of oxygen (pO2)/fraction of inspired oxygen (FiO2)≥ 150 or oxygen saturation (SpO2)/FiO2≥200 = 7; Mechanical ventilation, pO2/FiO2 \< 150 (SpO2/FiO2 \< 200) or vasopressors = 8; Mechanical ventilation, pO2/FiO2 \< 150 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) = 9; Dead = 10. A decrease in the score reflects an improvement.
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Medizinische Universität Innsbruck
Innsbruck, Austria
Kaiser Franz Josef Spital, 4. Medizinische Abteilung mit Infektions- und Tropenmedizin
Vienna, Austria
Medizinische Universität Wien
Vienna, Austria
The National University Hospital, Rigshospitalet
Copenhagen, Denmark
Herlev Gentofte Hospital
Herlev, Denmark
Nordsjællands Hospital
Hillerød, Denmark
Hvidovre Hospital
Hvidovre, Denmark
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Klinikum rechts der Isar, Technische Universität München
München, Germany
Regional State Budgetary Educational Institution "Clinical Hospital № 5, Barnaul"
Barnaul, Russia
...and 12 more locations
Time frame: Day 7, Day 10, Day 14, Day 28
Time to Hospital Discharge
The number of days from randomization to discharge from hospital was calculated (Kaplan-Meier analysis). Patients without hospitalization or without documented hospital discharge who completed the study or were early terminated before Day 28 were censored at the date of study completion or discontinuation, respectively. Patients who died before Day 28 were censored at the date of death even if early terminated before.
Time frame: Up to 28 days
Viral Ribonucleic Acid (RNA).
Viral RNA was assessed in blood samples using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and projected to RNA copies per mL.
Time frame: Day 1, Day 3, Day 5, Day 7, Day 14, and Day 28/End of study (EOS)
Time to a 2-point Decrease in WHO's 11-Point Score System
The time from randomization to an at least 2-point decrease in the WHO scale was calculated. The WHO Clinical Progression Scale provides a measure of illness severity across an 11 point range from 0 (not infected) to 10 (dead) as follows (scores 4-9 contain measures of respiratory failure): Uninfected, no viral DNA detected = 0; Asymptomatic, viral DNA detected = 1; Symptomatic, independent = 2; Symptomatic, assistance needed = 3; Hospitalized, no oxygen therapy = 4; Hospitalized, oxygen by mask or nasal prongs = 5; Hospitalized, oxygen by non-invasive ventilation (NIV) or high flow = 6; Intubation and mechanical ventilation, pO2/FiO2 ≥ 150 or SpO2/FiO2≥200 = 7; Mechanical ventilation, pO2/FiO2 \< 150 (SpO2/FiO2 \< 200) or vasopressors = 8; Mechanical ventilation, pO2/FiO2 \< 150 and vasopressors, dialysis, or ECMO = 9; Dead = 10. A decrease in the score reflects an improvement in disease status.
Time frame: Up to 28 days.
Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
The number of patients receiving mechanical ventilation and supplemental oxygen was evaluated.
Time frame: Up to 28 days
Time to First Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Time from randomization to first use of invasive mechanical ventilation was calculated (Kaplan-Meier analysis). Patients without documented invasive mechanical ventilation who completed the study, were early terminated or discharged from hospital before Day 28 were censored at the date of study completion, discontinuation or discharge from hospital, respectively.
Time frame: Up to 28 days
PaO2/FiO2 Value
The ratio in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) was assessed by analysis of patient's blood gas.
Time frame: Day 1, Day 7, Day 10, Day 14, and Day 28
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
The mSOFA score predicts intensive care unit mortality using clinical and laboratory variables. 5 organ systems (respiratory SpO2/FiO2; liver; cardiovascular/hypotension; Central nervous System/Glasgow Coma Score; renal/creatinine), all, except for liver, scored on a 0 to 4 scale (liver: 2-point scale: 0 or 3) according to specified criteria indicating severity, with the total score ranging from 0 to a maximum score of 19. A higher score reflects a worse disease state.
Time frame: Day -1 (Screening), Day 7, Day 10, Day 14, Day 28/End of study
Lymphocyte Count
Lymphocytes were assessed in blood samples from the patients.
Time frame: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
C-reactive Protein Levels
C-reactive protein was assessed in blood samples from the patients.
Time frame: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
D-Dimer
D-Dimer was assessed in blood samples from the patients.
Time frame: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Log-transformed Levels of LDH
Log transformed levels of LDH in blood were assessed as a surrogate marker for organ damage.
Time frame: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study