Clinical trial NCT04977960: Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19 Acute Respiratory Distress Syndrome
Keywords: COVID-19
potassium canrenoate
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: University of Milan
name: IRCCS Azienda Ospedaliero-Universitaria di Bologna
First posted: 2021-07-27
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label, 1:1 randomized parallel arms, Simon's two stage design, single centre.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: in-hospital death
timeFrame: At the event (discharge or death)
Secondary outcomes:
measure: Need of invasive mechanical ventilation throughout hospitalization
timeFrame: at discharge or death
measure: Duration of hospitalization for alive patients
timeFrame: From date of randomization until the date discharge or in-hospital death from any cause, whichever came first, assessed up to 48 months
measure: Drug intolerance
timeFrame: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
measure: Number of hypotensive events
timeFrame: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
measure: Number of hyperkaliemias events
timeFrame: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
measure: Number of renal failures
timeFrame: From the date of randomization until three days after the end of IMP administration (10 days after randomization)
measure: Change in Sequential Organ Failure Assessment (SOFA) score from randomization to 7 days after randomization
timeFrame: 7 days after randomization
measure: Change in inflammatory status
timeFrame: at 48 hours and 168 hours (7th day) from randomization
measure: Change in respiratory parameters
timeFrame: at 48 hours and 168 hours (7th day) from randomization
measure: Changes in features of pulmonary interstitial disease measured by chest X-Ray
timeFrame: at 7 days after randomization
measure: Changes in [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids
timeFrame: at randomization and at 48 and 168 hours (7th day) from randomization
measure: 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)
timeFrame: at randomization and at 48 and 168 hours (7th day) from randomization
Other outcomes:
Locations:
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Marco Vicenzi, MD
role: PRINCIPAL_INVESTIGATOR
References: