Potassium canrenoate 200mg/10ml solution for injection ampoules

IntroductionHeart failure with reduced ejection fraction (HFrEF) represents a major clinical and economic burden in Italy, driven by an aging population. Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of guideline-recommended therapy. Eplerenone has demonstrated efficacy in reducing mortality and hospitalizations but remains underutilized. This study assessed the budget impact of increasing eplerenone use in eligible patients with HFrEF from national and regional perspectives.MethodsA budget impact analysis (BIA) was conducted over a 3-year horizon from the perspective of the Italian National Health Service (INHS). Two scenarios were compared: Current (observed MRA use) and Projected (increased eplerenone uptake). Model inputs included eligible population, treatment distribution, drug acquisition costs, and clinical outcomes (all-cause mortality, hospitalizations, renal impairment, hyperkalemia, and gynecomastia) with associated costs. Clinical inputs were derived from a network meta-analysis (NMA); cost inputs from Italian literature and national tariffs.ResultsTotal expenditure increased from €598.6 million (M) to €600.6 M over 3 years, corresponding to a net budget impact of + €2.01 M (+ 0.34%), with annual increments of €880,000 (year 1), €885,000 (year 2), and €245,000 (year 3). Increased eplerenone use resulted in higher costs (+ €35.07 M), driven by drug acquisition and hospitalization costs, partially offset by mortality-related savings (-€3.62 M). These were partially counterbalanced by reductions in other MRAs (spironolactone - €6.37 M, potassium canrenoate - €8.32 M, canrenone - €18.37 M), mainly due to fewer hospitalizations, renal events, and a lower drug volume. Results were primarily driven by clinical parameters for eplerenone, particularly NMA-derived hazard ratios for hospitalization and all-cause mortality. The net budget impact was modest in relative terms (ConclusionsGreater adoption of eplerenone was associated with a modest net increase in healthcare expenditure for the INHS, corresponding to approximately €3.20 per treated patient per year and consistent with substantial budget neutrality. The budget impact reflects both treatment redistribution and differences in clinical outcomes across MRAs. Expanding eplerenone use in line with guideline-recommended therapy may be achieved at a limited additional cost, while offering a more favorable renal and selectivity profile relative to other MRAs.

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Introduction Ischaemia/reperfusion injuries (IRIs) are associated with poorer survival of kidney grafts from expanded criteria donors. Preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) prevent acute and chronic post-ischaemic renal dysfunction by limiting IRI. However, data concerning the safety of MRAs in brain-dead donor patients are scarce. We seek to investigate the tolerance of MRAs on the haemodynamics in this population. Methods and analysis CANREO-PMO is a randomised, controlled, single-centre, double-blind study. Brain-dead organ donors hospitalised in intensive care are randomised 1:1 after consent to receive 200 mg potassium canrenoate or its matching placebo every 6 hours until organ procurement. The primary outcome is a hierarchical composite endpoint that includes: (1) cardiocirculatory arrest, (2) the impossibility of kidney procurement, (3) the average hourly dose of norepinephrine/epinephrine between randomisation and departure to the operating room, and (4) the average hourly volume of crystalloids and/or colloids received. Thirty-six patients will be included. The secondary endpoints evaluated among the graft recipients are the: (1) vital status of the kidney graft recipients and serum creatinine level with estimated glomerular filtration rate (GFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) at 3 months after renal transplantation, (2) percentage of patients dependent on dialysis and/or with an estimated GFR <20 mL/min/1.73 m 2 at 3 months, (3) vital status of the kidney graft recipients at 3 months, and (4) vital status of the kidney graft recipients and creatinine levels (in μmol/L), with the estimated GFR according to CKD-EPI (in mL/min/1.73 m 2 ), at 1 year, 3 years and 10 years after transplantation. Ethics and dissemination This trial has full ethical approval (Comité de Protection des Personnes: CPP Ouest II-ANGERS, France), and the written consent of relatives will be obtained. Results will be reported at conferences, peer-reviewed publications and using social media channels. Trial registration number NCT04714710 .

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In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon’s test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation.

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In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation.

Abstract licence: CC BY 4.0

In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the suppressive effects of MRAs on the activities of hormone synthase. The probable factors of cytochrome P-450 reduction, both in microsomes and mitochondria, have also been considered: (1) one of the spironolactone metabolite forms had destructive function, except canrenone, (2) 7α-thio-spironolactone was an obligatory intermediate in the spironolactone-induced CYP450 decrease, and (3) the contributing steroids should have 7α-methylthio or 7α-methylsulfone groups. In previous clinical research, spironolactone-body-containing cells showed a type II pattern of enzyme activity (i.e., enhanced 3β-hydroxysteroid dehydrogenase, glucose-6-phosphate, and NADP-isocitrate dehydrogenase activities and weaken succinate dehydrogenase activity), and the subcapsular micronodules composed of spironolactone-body-containing cells also exhibited a type II pattern and excess aldosterone secretion, indicating that the subcapsular micronodules might be the root of aldosterone-producing adenoma. Moreover, combined with the potential impeditive function to aldosterone secretion, a few cases of spontaneous remission of primary aldosteronism, with normal ranges of blood pressure, plasma potassium, plasma renin activity, and aldosterone renin ratio, have been reported after long-term treatment with MRAs.

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BackgroundArterial hypertension is the most common cardiovascular comorbidity in atrial fibrillation (AF). Few studies investigated management strategies of hypertension in AF.Materials and methodsWe included 5769 AF patients on oral anticoagulants from the nationwide ongoing Italian START registry. We investigated the prescription of antihypertensive drugs and mortality risk. Subgroup analyses according to sex and major cardiovascular comorbidities were performed.ResultsMean age was 80.8 years, 46.1% were women; 80.3% of patients were hypertensive. Furosemide (30.1%) was the most frequent diuretic followed by hydrochlorothiazide (15.4%) and potassium canrenoate (7.9%). 61.1% received β-blockers: 34.2% bisoprolol, 6.2% atenolol. Additionally, 36.9% were on angiotensin converting enzyme inhibitors (ACE-I): ramipril (20.9%), enalapril (5.3%) and perindopril (2.8%); 31.7% were on angiotensin receptors blockers (ARBs): valsartan (7.6%) and irbesartan (6.4%). Amlodipine and lercanidipine were prescribed in 14.0% and 2.3%, respectively. ACE-I (p ConclusionA lower mortality risk was found in AF patients on ACE-I/ARBs. Different prescription patterns of antihypertensive drugs between men and women do exist.

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A post-authorisation safety study (PASS) was conducted to assess the impact of LysaKare (2.5% Lysine-Arginine solution) on serum potassium concentrations and its safety/tolerability profile in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET) eligible for 177Lu-DOTATATE treatment. In a phase IV, multicentre, single-arm, open-label PASS, adults with somatostatin receptor-positive GEP-NET who were eligible for 177Lu-DOTATATE treatment received 1000 mL of LysaKare (monotherapy) intravenously over 4 h. The primary endpoint was the change in serum potassium levels over the course of 24 h. Secondary endpoints included the incidence of LysaKare-related adverse events (AEs) and changes in laboratory parameters. Forty-one patients were treated (median age, 57 years; 92.7% White and 7.3% Black; 53.7% male) and 40 completed post-treatment follow-up. Mean (standard deviation [SD]) serum potassium was 4.33 (0.397) mmol/L pre-dose, increasing by 0.60 (0.666) mmol/L after 4 h (time to maximum change, range, 2-24 h) before decreasing to around the pre-dose level: the mean (SD) increase after 24 h was 0.07 (0.396) mmol/L. Other electrolytes and blood gas components mostly showed transient changes that lasted ~24 h. A general trend of transient metabolic acidosis was also observed based on laboratory values. Serum potassium grade increased from baseline in 41.5% of patients. By comparison, five patients (12.2%) had a treatment-related AE of hyperkalaemia (grade 3, n = 1); all resolved within 24 h, either without treatment (n = 3) or following intravenous furosemide (n = 2). There were no serious AEs and no AEs leading to treatment discontinuation/interruption. This PASS identified no new safety signals attributable to LysaKare. Trial registration: EudraCT, 2019-004073-76. Registered 20/08/2020.

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