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

May 16, 2022 updated by: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

MINECRAFT Study: MINEralcorticoid Receptor Antagonism With CanRenone As eFfective Treatment in Moderate to Severe ARDS in COVID-19, a Phase 2 Clinical Trial.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
180

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
NO_INTERVENTION: Reference group

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: Experimental Group
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
potassium canrenoate for 7 days in addition to maximal medical treatment
Other Names:
  • Canrenone

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
in-hospital death
Time Frame: At the event (discharge or death)
patients discharged to a long-term care facility will be classified as "discharged alive"
At the event (discharge or death)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Need of invasive mechanical ventilation throughout hospitalization
Time Frame: at discharge or death
Researchers will record if mechanical ventilation has been required during hospitalization (YES) or not (NO)
at discharge or death
Duration of hospitalization for alive patients
Time Frame: 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
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
Time Frame: 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
From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Number of hypotensive events
Time Frame: 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)
From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Number of hyperkaliemias events
Time Frame: 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
From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Number of renal failures
Time Frame: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
defined as eGFR <30 ml/min
From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Change in Sequential Organ Failure Assessment (SOFA) score from randomization to 7 days after randomization
Time Frame: 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
7 days after randomization
Change in inflammatory status
Time Frame: at 48 hours and 168 hours (7th day) from randomization
CRP levels, IL-6, Ddimer and Ferritin
at 48 hours and 168 hours (7th day) from randomization
Change in respiratory parameters
Time Frame: at 48 hours and 168 hours (7th day) from randomization
Heart Rate, Blood Pressure (mmHg), PaO2/FiO2 (mmHg), alveolar-arterial gradient (mmHg)
at 48 hours and 168 hours (7th day) from randomization
Changes in features of pulmonary interstitial disease measured by chest X-Ray
Time Frame: at 7 days after randomization
at 7 days after randomization
Changes in [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids
Time Frame: 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
at randomization and at 48 and 168 hours (7th day) from randomization
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)
Time Frame: 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
at randomization and at 48 and 168 hours (7th day) from randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
IRCCS Azienda Ospedaliero-Universitaria di Bologna
University of Milan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marco Vicenzi, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2022

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2023

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2021

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 27, 2021

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MINECRAFT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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