Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19 (MINECRAFT)

Institute of Hospitalization and Scientific Care (IRCCS)

Status and phase: Unknown; Phase 2

Conditions: COVID-19 Acute Respiratory Distress Syndrome

Treatments: Drug: Potassium Canrenoate

Study type: Interventional

Funder types: Other

Identifiers

NCT04977960

MINECRAFT

Details and patient eligibility

About

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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 2 patient groups

Reference group

No Intervention group

Description:

Patients randomized to the Reference Group will receive the standard-of-care treatments, according to institutional procedures in force: * Dexamethasone i.v. 6 mg die for consecutive 5 days * Methylprednisolone i.v. 40 mg bid for consecutive 10 days * Low-molecular-weight-heparin i.v. at standardized dose of 70 UI/kg twice * Remdesivir i.v. 200 mg in bolus (1st day) then 100 mg die for 4 days; remdesivir will be used only in patients supported with low-flow nasal cannula oxygen or Venturi mask * Antibiotic therapy: * azithromycin: 500 mg/die per os for 5 days * ceftriaxone: 2 g i.v. die for 8 days

Experimental Group

Experimental group

Description:

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

Treatment:

Drug: Potassium Canrenoate