COVID-19 Acute Respiratory Distress Syndrome
Conditions
Keywords
COVID-19, potassium canrenoate
Brief summary
The main aim of the study is to estimate the potential efficacy of i.v. canrenone as add-on therapy on maximal medical treatment versus maximal medical treatment alone in treating moderate-to-severe ARDS due to SARS-CoV-2.
Interventions
potassium canrenoate for 7 days in addition to maximal medical treatment
Sponsors
University of Milan
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, 1:1 randomized parallel arms, Simon's two stage design, single centre.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 - 80 y.o. Since over eighties are very fragile patients, a lot of confounding unpredictable events may interfere with the trial analyses; thus, these patients will be excluded from this exploratory proof-of-concept trial; * COVID-19 diagnosis through swab within 14 days from the beginning of symptoms * Hospitalization for moderate to severe ARDS (as determined by PaO2/FiO2 ≤300 mmHg at admission) * Serum concentration of potassium ≤4.5 mEq/L * Consent to participate
Exclusion criteria
* Invasive mechanical ventilation * I.v. hydratation with Darrow's solution or half-strength Darrow's solution underway * Acute cardiovascular event (acute myocardial infarction, acute ischaemic stroke) * Current malignant disease * Creatinine \>1.8 mg/dL (for women) and \>2.0 mg/dL (for men) or glomerular filtration rate \<50 mL/mm * Systolic blood pressure \<110 mmHg and/or diastolic blood pressure \<60 mmHg * Known or suspected hypersensitivity to canrenone * Hyponatremia * Anuria * Familial history of porphyria * Pregnancy and breastfeeding * known or suspected hypersensitivity to canrenone * Inclusion in any other pharmacological clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| in-hospital death | At the event (discharge or death) | patients discharged to a long-term care facility will be classified as discharged alive |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of hospitalization for alive patients | From date of randomization until the date discharge or in-hospital death from any cause, whichever came first, assessed up to 48 months | from randomization to discharge |
| Drug intolerance | From the date of randomization until three days after the end of IMP administration (10 days after randomization) | measured as number of AR and SAR |
| Number of hypotensive events | From the date of randomization until three days after the end of IMP administration (10 days after randomization) | defined as systolic blood pressure constantly \<90 mmHg and diastolic blood pressure constantly \<60 mmHg) |
| Number of hyperkaliemias events | From the date of randomization until three days after the end of IMP administration (10 days after randomization) | defined as \[K+\]hematic \>5.1 mEq/L |
| Number of renal failures | From the date of randomization until three days after the end of IMP administration (10 days after randomization) | defined as eGFR \<30 ml/min |
| Need of invasive mechanical ventilation throughout hospitalization | at discharge or death | Researchers will record if mechanical ventilation has been required during hospitalization (YES) or not (NO) |
| Change in inflammatory status | at 48 hours and 168 hours (7th day) from randomization | CRP levels, IL-6, Ddimer and Ferritin |
| Change in respiratory parameters | at 48 hours and 168 hours (7th day) from randomization | Heart Rate, Blood Pressure (mmHg), PaO2/FiO2 (mmHg), alveolar-arterial gradient (mmHg) |
| Changes in features of pulmonary interstitial disease measured by chest X-Ray | at 7 days after randomization | — |
| Changes in [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids | at randomization and at 48 and 168 hours (7th day) from randomization | \[K+\]hematic will be expressed as mEq/L Plasmatic Renin Activity will be expressed as µUI/mL Hematic Concentration of AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids will be expressed as ng/mL |
| Correlation between levels of [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids, at basal level (randomization) and clinical outcomes (in-hospital death, need of invasive mechanical ventilation, SOFA score) | at randomization and at 48 and 168 hours (7th day) from randomization | \[K+\]hematic will be expressed as mEq/L Plasmatic Renin Activity will be expressed as µUI/mL Hematic Concentration of AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids will be expressed as ng/mL |
| Change in Sequential Organ Failure Assessment (SOFA) score from randomization to 7 days after randomization | 7 days after randomization | A score from 0 (better outcome) to 4 (worst outcome) for six different systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems) will be assessed and recorded in CRF |
Contacts
Primary ContactMarco Vicenzi, MD
Outcome results
None listed