Table 3 Study outline (SPIRIT)

Enrolment

 screening

inclusion and exclusion criteria, informed consent, pregnancy test

X

 randomisation

randomisation within 6 hours after study enrolment and

X

Intervention

 study medication

start study medication within 3 hours after randomisation

X

Assessments

 adverse events (AEs) and severe AEs

X

X

X

X

X

X

 demographic variables

age, sex, body height and weight

X

 (SARS-CoV-2) medical history

date of: first record of SARS-CoV-2 and first symptoms, symptoms of SARS-CoV-2 infection, SARS-Cov-2 immunisation status, date of hospital admission, type of admission, place before patient transfer/admission, nicotine abuse, family history of heart attack, physical activity, accompanying infections

X

 cardiovascular/general comorbidities and previous findings

Charlson comorbidity index, heart attack, congestive heart failure, coronary heart disease, angina pectoris, valvular heart disease, arrhythmias, arterial hypertension, peripheral arterial disease

Previous findings echocardiography: rhythm, imaging quality, ejection fraction, pericardial effusion, aortic/mitral/tricuspid/pulmonary valve stenosis and/or insufficiency, VCI diameter, VCI collapse, RAP, SPAP, MPAP, right ventricular function

X

 clinical status and vital signs

COVID-19 inflammation score [25], WHO-COVID-19-Progression Scale [26]

consciousness, Glasgow Coma Scale, CAM-ICU, blood pressure, mean arterial blood pressure, heart rate, oxygen saturation and FiO₂, paO₂ / FiO₂ ratio, respiratory rate, urine production

X

X

X

X

X

 organ replacement therapy

administration of oxygen, high-flow oxygen therapy, non-invasive ventilation, invasive ventilation, ECMO, kidney and liver replacement

X

X

X

X

 organ dysfunction

acute encephalopathy, thrombocytopenia, arterial hypoxemia, arterial hypotension, renal dysfunction, metabolic acidosis, septic shock

X

X

X

X

 sepsis-3-criteria

SOFA-score

X

X

X

X

 medication

antiplatelet drugs, anticoagulation, immunosuppressants, angiotensin converting enzyme inhibitors, catecholamines

X

X

X

X

 blood and urine tests: routine

COVID-19-Panel (i.a. troponin, NT-proBNP, PCT, sodium, potassium, chloride, calcium, iron, phosphate, alpha-1antitrypsin, urea, creatinine, bilirubin, albumin, ASAT, ALAT, Gamma-GT, AP, cholinesterase, GLDH, LDH, CK, CK-MB, haptoglobin, haematocrit, haemoglobin, thrombocytes, antithrombin-III, base excess (B.E.) art., bicarbonate (SBC) art., pH art., lactate, Quick, LDL-cholesterol, HDL-cholesterol, HbA1c, IL-6, ferritin, triglycerides, fibrinogen, leucocytes, lymphocytes, D-Dimer, partial thromboplastin time)

X

X

X

X

 blood and urine sampling:

supplementary scientific programme

date and time

X

X

X

 virology

SARS-CoV-2 PCR

X

X

X

X

 transthoracic echocardiography (TTE)

rhythm, quality, ejection fraction, pericardial effusion, aortic/mitral/tricuspid/pulmonary valve stenosis and/or insufficiency, VCI diameter, VCI collapse, RAP, SPAP, MPAP, right ventricular function

X

X

 clinical endpoints and cardiovascular events after randomisation

thromboembolic events; cardiovascular events: cardiopulmonary resuscitation, arrhythmia,

cardiomyopathy/reduced left ventricular function, STEMI/NSTEMI, angina pectoris, valve stenosis, others

X

X

X

X

X

 cumulative endpoints

ventilation-free days, vasopressor-free days, renal replacement therapy-free days, occurrence of severe acute respiratory distress syndrome (Berliner criteria+ PaO₂/FiO₂ ≤100 mmHg with PEEP ≥5 cm H₂O), medication prohibited by the study protocol and SARS-CoV-2-specific therapies

X

 survival status /place of treatment

survival status/date of death, current place of treatment

X

X

X

X

X

 general disease progression/patient history after randomisation

current residence, hospital re-admissions, infections, rehabilitation and outpatient therapies

X

X

 COVID-19 (long-term) sequelae

checklist (i.a. dyspnoea, taste and smelling disorders, psychological sequela)

X

 quality of life: EQ-5D-3L

EQ-5D-3L

X

X

 end of study data and cumulative treatment data

irregular end of participation, withdrawal of consent to participate, ICU treatment and length of ICU stay since randomisation, length of hospital stay since hospital admission and since randomisation, pregnancy

X