OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure

Korábbi kezelés

• Prior history of hypersensitivity (other than hyperkalemia) to a MRA, or SZC
• Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymp-tomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted

Más betegség

• HF due to restrictive cardiomyopathy, hypertrophic (obstructive) cardio-myopathy or primary valvular disease
• Current/recent (within 3 months) hospitalization due to myocardial infarc-tion, unstable angina pectoris, coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or other interven-tions (valvular repair/replacement, cardiac transplantation or implantation of a ventricular assistance device)
• Advanced malignancy requiring treatment

Laborértékek

• eGFR \< 30 ml/min/1,73 m2 (modified MDRD formula)
• History of QT prolongation associated with other medications that required discontinuation of that medication.
• Congenital long QT syndrome.
• QTc(f) \> 550 msec

Egyéb

• Subjects should not enter the study if any of the following exclusion criteria are ful-filled:
• Symptomatic hypotension (\< 90/60 mmHg)
• Ongoing or planned dialysis
• Currently pregnant (confirmed with positive pregnancy test) or planned pregnancy or breast-feeding
• Can not sign informed consent.

• Recruiting will take place mainly from specialist care at University hospitals or Province hospitals in Sweden. But some of patients might have simultaneous follow-up at primary care as well.
• Each subject should meet all of the inclusion criteria and none of the exclusion criteria for this study. Under no circumstances can there be exceptions to this rule.
• For inclusion in the study subjects should fulfil the following criteria:
• Obtain signed informed consent prior to any study specific procedures
• \>18 yrs.
• LVEF ≤ 40% within past 2 years (including recovered EF later on).
• NYHA II-IV.
• On optimal treatment including ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor, as per physician´s judgement.
• Suboptimal treatment with MRA (defined as: no use or ≤ 25 mg daily)
• And one of following:
  • Prior hyperkalemia (S-K\> 5.0 mmol/L or P-K\> 4.8 mmol/L\*) during MRA treat-ment within last 24 months, and current S-K ≤ 5.0 or P-K ≤ 4.8 mmol/L
  • Current S-K 4.5-5.0 mmol/L or P-K 4.3-4.8 mmol/L, and potential risk of hyper-kalemia as indicated by eGFR 30-45 ml/min/1,73 m2 (modified MDRD formula)
  • Current S-K 5.1-5.9 mmol/L or P-K 4.9-5.7 mmol/L
  • Corresponding plasma K (P-K) level is 0.2 mmol lower than serum K(S-K) (The Nordic Reference Interval Project).
  • Depending on the S-K status during screening, patients are divided into two groups before treatment initiation /run-in:
• Group 1: Patients who are hyperkalemic (S-K 5.1 - 5.5 mmol/L measured within last 2 weeks)
• Group 2: Patients who are normokalemic (S-K 3.5 - 5.0 mmol/L) during screening but are at a high risk of developing hyperkalemia associated with MRA initiation / increase. Namely, one (or both) of the following:
  • Prescription of MRA within last 12 months and documented hyperkalemia after MRA prescription
  • S-K 4.5-5.0 mmol/L and GFR \< 45 mL/min/1,73 m2
  • Note: All S-K related limits in this protocol concern serum measurements. In Sweden it is plasma that is analyzed, which makes 4.8 mmol/l (plasma) equivalent to 5.0 mmol/L(serum)