The role of sodium zirconium cyclosilicate in uptitrating spironolactone in patients with heart failure with reduced ejection fraction and at high-risk for hyperkalemia

Not Applicable

Recruiting

• Conditions: Hyperkalemia; Heart failure; D006947

• Registration Number: JPRN-jRCTs031220568
• Lead Sponsor: Kida Keisuke

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-01-13
• Last Update Posted: 22 January 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 266

Inclusion Criteria

(1) Individuals who have been briefed on the nature of the study and provided written informed consent to participate in the study
(2) Aged 20 to 90 years old
(3) Left ventricular ejection fraction of less than 50%
(4) Estimated glomerular filtration rate (eGFR) of 15-45 mL/min/1.73 m2
(5) Potassium level exceeds 5.0 mEq/L
(6) Spironolactone has been introduced at 12.5-37.5 mg
(7) NT-proBNP level of more than 400 pg/mL (if the patient had a history of hospitalization for heart failure)
(8) NT-proBNP level of more than 600 pg/mL (if the patient had no history of heart failure hospitalization)
(9) Currently taking a beta-blocker and either an ACE inhibitor/ARB/ARNi (regardless of dose), unless contraindicated

Exclusion Criteria

(1) Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or organic valvular disease
(2) Renal artery stenosis
(3) Chronic dialysis (hemodialysis, peritoneal dialysis)
(4) Use of NSAIDs within 1 week and/or inability to discontinue
(5) QT prolongation; QTc (f) >550 msec
(6) Symptomatic bradycardia without pacemaker or concomitant symptomatic II (Mobitz type 2) or III degree AV block
(7) History of drug-induced QT prolongation with drug discontinuation
(8) Congenital long QT syndrome
(9) Use of lactulose, rifaximin, or other non-absorbable antibiotics for hyperammonemia
(10) Use of resin (sevelamer acetate, sodium polystyrene sulfonate, etc.), calcium acetate, calcium carbonate, or lanthanum carbonate within 7 days prior to the first dose of the study drug
(11) Patients who are pregnant or lactating or those who wish to become pregnant during the study period
(12) Use of potassium-lowering drugs other than study drugs (calcium polystyrene sulfonate, sodium polystyrene sulfonate)
(13) Patients who are already taking over 50 mg of spironolactone
(14) Symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
(15) Patients who are judged to be unsuitable for enrollment by the principal investigator or sub-investigator

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the achievement of spironolactone 50 mg/day at the end of the double-blind period and without use of rescue therapy* for hypokalemia or hyperkalemia at any time during the double-blind period.<br>*Definition of rescue therapy <br>1) Rescue treatment for hyperkalemia<br>Calcium gluconate<br>Glucose-insulin therapy<br>Potassium adsorbent other than SZC<br>Dialysis therapy<br>2) Rescue treatment for hypokalemia<br>Potassium replacement therapy (oral or intravenous)<br><br>The numerator is the number of patients who achieved the above criteria (i.e., responder), and the denominator is the number of patients who were randomly allocated. The patient who meets the following conditions is classified as a non-responder.<br>- Patients who discontinued study treatment (SZC/placebo) or withdrew from study participation during the double-blind period.

Secondary Outcome Measures

Name	Time	Method
- Achievement of a potassium level of >5.5 mEq/L in the double-blind period<br>- Time to first use of rescue therapy and/or MRA dose reduction for hyperkalemia in the double-blind period<br>- Changes in spironolactone dose over double-blind period<br>- Achievement of target dose of ACE inhibitors and other GDMT, including ARBs and ARNi [target dose (per day) for lisinopril (10 mg), enalapril (10 mg), candesartan (8 mg), and sacubitril/valsartan 400 mg]<br>- Achievement a target dose of 50% or higher of other GDMT, including beta-blockers [target dose (per day) for carvedilol (20 mg) and bisoprolol (5 mg)], ACE inhibitors, ARBs, and ARNi<br>- Change in KCCQ, PGIC, NYHA class <br>- Change in eGFR, NT-proBNP, urinary Na, K, Cl, Cr, BUN, and UACR