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

NCT04977960 | Unknown Phase 2

• 1 other identifier: MINECRAFT
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

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.

Conditions

COVID-19 Acute Respiratory Distress Syndrome

Keywords

COVID-19; potassium canrenoate

Outcome Measures

Primary Outcomes (1)

• in-hospital death

  patients discharged to a long-term care facility will be classified as "discharged alive"

  At the event (discharge or death)

Secondary Outcomes (12)

• Need of invasive mechanical ventilation throughout hospitalization

  at discharge or death

• 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

• Drug intolerance

  From the date of randomization until three days after the end of IMP administration (10 days after randomization)

• Number of hypotensive events

  From the date of randomization until three days after the end of IMP administration (10 days after randomization)

• Number of hyperkaliemias events

  From the date of randomization until three days after the end of IMP administration (10 days after randomization)

Study Arms (2)

Reference group

NO INTERVENTION

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

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

Drug: Potassium Canrenoate

Interventions

Potassium Canrenoate DRUG

potassium canrenoate for 7 days in addition to maximal medical treatment

Also known as: Canrenone

Experimental Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• University of Milan: collaborator
• IRCCS Azienda Ospedaliero-Universitaria di Bologna: collaborator

MeSH Terms

Conditions

COVID-19

Interventions

Canrenoic Acid; Canrenone

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Marco Vicenzi, MD

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco Vicenzi, MD

CONTACT

+390255033537; marco.vicenzi@policlinico.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, 1:1 randomized parallel arms, Simon's two stage design, single centre.

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: July 27, 2021
• Study Start: September 1, 2022
• Primary Completion: May 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 20, 2022

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share