Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19
- Conditions
- COVID-19 Acute Respiratory Distress Syndrome
- Interventions
- Registration Number
- NCT04977960
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 180
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Group Potassium Canrenoate Patients randomized in the Experimental Group will receive canrenone as add-on therapy to standard-of-care treatments. Different starting doses of i.v. canrenone will be administrated in a single or double infusion per day, for 7 days, according to the serum concentration of potassium at randomization
- Primary Outcome Measures
Name Time Method in-hospital death At the event (discharge or death) patients discharged to a long-term care facility will be classified as "discharged alive"
- Secondary Outcome Measures
Name Time Method 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)
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
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)
Change in inflammatory status at 48 hours and 168 hours (7th day) from randomization CRP levels, IL-6, Ddimer and Ferritin
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
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
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
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)
Changes in features of pulmonary interstitial disease measured by chest X-Ray at 7 days after randomization 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
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