Status:
ACTIVE_NOT_RECRUITING
OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure
Lead Sponsor:
Michael Fu
Collaborating Sponsors:
AstraZeneca
Göteborg University
Conditions:
Heart Failure
Hyperkalemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Mineralocorticoid receptor antagonists (MRA) is one of cornerstones in the treatment of heart failure with reduced ejection fraction (HFrEF). However, MRA has been extremely under-used globally. The m...
Detailed Description
Target subject population Stable and symptomatic patients with chronic heart failure and LVEF ≤ 40% despite Guideline-Directed Medical Treatment (ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor, MRA) at...
Eligibility Criteria
Inclusion
- 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.
- Inclusion criteria
- 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)
Exclusion
- Subjects should not enter the study if any of the following exclusion criteria are ful-filled:
- Symptomatic hypotension (\< 90/60 mmHg)
- eGFR \< 30 ml/min/1,73 m2 (modified MDRD formula)
- 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)
- Ongoing or planned dialysis
- Prior history of hypersensitivity (other than hyperkalemia) to a MRA, or SZC
- Advanced malignancy requiring treatment
- History of QT prolongation associated with other medications that required discontinuation of that medication.
- Congenital long QT syndrome.
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymp-tomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
- QTc(f) \> 550 msec
- Currently pregnant (confirmed with positive pregnancy test) or planned pregnancy or breast-feeding
- Can not sign informed consent.
Key Trial Info
Start Date :
September 1 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2025
Estimated Enrollment :
110 Patients enrolled
Trial Details
Trial ID
NCT04789239
Start Date
September 1 2021
End Date
December 31 2025
Last Update
July 4 2025
Active Locations (2)
Enter a location and click search to find clinical trials sorted by distance.
1
Section of Cardiology, Sahlgrenska University Hospital-Östra Hospital
Gothenburg, Västra Götalanddsregion, Sweden, 41650
2
Sahlgrenska University Hospital-Ostra Hospital
Gothenburg, Sweden, 41650