COVID-19 Acute Respiratory Distress SyndromePhase 2MINECRAFTNCT04977960
Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19
A Phase 2 study testing Potassium Canrenoate in people with COVID-19 Acute Respiratory Distress Syndrome, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- COVID-19 Acute Respiratory Distress Syndrome
- What is being tested?
- Potassium Canrenoate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- Sep 2022to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- Known or suspected hypersensitivity to canrenone
- Hyponatremia
- Anuria
- Familial history of porphyria
- Pregnancy and breastfeeding
- known or suspected hypersensitivity to canrenone
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
- Being tested
- Potassium Canrenoate
- Keywords
- COVID-19, potassium canrenoate
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium CanrenoateDrug
Also called Canrenone
potassium canrenoate for 7 days in addition to maximal medical treatment
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Potassium Canrenoate |
What is being measured
The primary outcome is the main question the study is designed to answer.
in-hospital death
patients discharged to a long-term care facility will be classified as "discharged alive"
Measured: At the event (discharge or death)
Secondary outcomes (12)
Need of invasive mechanical ventilation throughout hospitalization
Researchers will record if mechanical ventilation has been required during hospitalization (YES) or not (NO)
Measured: at discharge or death
Duration of hospitalization for alive patients
from randomization to discharge
Measured: 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
measured as number of AR and SAR
Measured: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Number of hypotensive events
defined as systolic blood pressure constantly <90 mmHg and diastolic blood pressure constantly <60 mmHg)
Measured: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Number of hyperkaliemias events
defined as [K+]hematic >5.1 mEq/L
Measured: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
Number of renal failures
defined as eGFR <30 ml/min
Measured: 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
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
Measured: 7 days after randomization
Change in inflammatory status
CRP levels, IL-6, Ddimer and Ferritin
Measured: at 48 hours and 168 hours (7th day) from randomization
Change in respiratory parameters
Heart Rate, Blood Pressure (mmHg), PaO2/FiO2 (mmHg), alveolar-arterial gradient (mmHg)
Measured: at 48 hours and 168 hours (7th day) from randomization
Changes in features of pulmonary interstitial disease measured by chest X-Ray
Measured: at 7 days after randomization
Changes in [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids
[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
Measured: 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)
[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
Measured: at randomization and at 48 and 168 hours (7th day) from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study startSep 2022 (estimated)
- Primary completionMay 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19 Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open label, 1:1 randomized parallel arms, Simon's two stage design, single centre.
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Milan, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Responsible party
- Sponsor
- Investigators
- Marco Vicenzi, MD, Principal investigator, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04977960
- Sponsor's protocol ID
- MINECRAFT
- Acronym
- MINECRAFT
- Status last verified
- Jul 2021
- First submitted
- 21 Jul 2021
- Last updated
- 20 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MINECRAFT Study: MINEralcorticoid Receptor Antagonism With CanRenone As eFfective Treatment in Moderate to Severe ARDS in COVID-19, a Phase 2 Clinical Trial.
- ClinicalTrials.gov ID
- NCT04977960
- Acronym / sponsor ID
- MINECRAFT / MINECRAFT
- Keywords
- COVID-19, potassium canrenoate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Collaborators
- University of Milan, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Study start
- Sep 2022 (estimated)
- Primary completion
- May 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 27 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open label, 1:1 randomized parallel arms, Simon's two stage design, single centre.
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Potassium CanrenoatePatients 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Potassium CanrenoateAlso: Canrenonepotassium canrenoate for 7 days in addition to maximal medical treatment | Drug | Experimental Group |
Primary outcome
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"
12 secondary outcomes
Need of invasive mechanical ventilation throughout hospitalization
Time frame: 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
Drug intolerance
Time frame: 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)
Number of hyperkaliemias events
Time frame: 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)
Change in Sequential Organ Failure Assessment (SOFA) score from randomization to 7 days after randomization
Time frame: 7 days after randomization
Change in inflammatory status
Time frame: 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
Changes in features of pulmonary interstitial disease measured by chest X-Ray
Time frame: 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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Vicenzi, MD principal investigator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Potassium Canrenoate in people with COVID-19 Acute Respiratory Distress Syndrome, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 May 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Vicenzi, MD (+390255033537, marco.vicenzi@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
in-hospital death (time frame: At the event (discharge or death)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2022.