OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosili-cate in Heart Failure -Extension (OPRA-HF Extension) (OPRA-HF Extens)

A multicenter, randomized, controlled study in Sweden (n=110). This study consists of 2 phases: 1) open-label run-in within approximately 2 months, and 2) randomized, double-blinded and placebo-controlled treatment for 6 months.

The open-label phase, in turn, consists of three periods: up-titration (normally 1 - 2 weeks, and longer in some cases), correction (maximum 72 hours) and maintenance (4 - 7 weeks).

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: potassium binder

Detailed Description

A multicenter, randomized, controlled study in Sweden (n=110). This study consists of 2 phases: 1) open-label run-in within approximately 2 months, and 2) randomized, double-blinded and placebo-controlled treatment for 6 months.

The open-label phase, in turn, consists of three periods: up-titration (normally 1 - 2 weeks, and longer in some cases), correction (maximum 72 hours) and maintenance (4 - 7 weeks).

Eligible study population:

1. >70 yrs.
2. Regardless of LVEF but EF measured within past 2 years. For HFpEF echo criteria defined by ≥2 of: LV wall thickness ≥ 12 mm; LV mass index (BSA indexed LVH): male >115 g/m2, female >95 g/m2; relative wall thickness ≥0.42; E/e' ≥15 in sinus rhythm (or > 11 in the setting of atrial fibrillation); tricuspid regurgitation velocity >2.8 m/s; Left atrial volume index >34 ml/m2.
3. GFR ≥ 20 mL/min/1,73 m².
4. NYHA II-IV.
5. On optimal treatment as per physician´s judgement including ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor för HFrEF/HFmrEF, and SGLT2 inhibitors in HFpEF
6. Suboptimal treatment with MRA (defined as: no use or ≤ 25 mg daily
7. And one of following:

1) Prior hyperkalemia (S-K> 5.0 mmol/L or P-K> 4.8 mmol/L*) during MRA treatment within last 24 months, and current S-K ≤ 5.0 or P-K ≤ 4.8 mmol/L 2) Current S-K 4.5-5.0 mmol/L or P-K 4.3-4.8 mmol/L, and potential risk of hyperkalemia as indicated by eGFR 30-45 ml/min/1,73 m2 3) 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). Hyperkalemia is defined as P-K > 4,8 mmol/L or S-K >5,0 mmol/L.

Detailed inclusion and exclusions are described in Clinical Trial Org (NCT 047809239)

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Liangxiong Fu; Phone Number: 0739228176; Email: michael.fu@gu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. >70 yrs. 2. Regardless of LVEF but EF measured within past 2 years. For HFpEF echo criteria defined by ≥2 of: LV wall thickness ≥ 12 mm; LV mass index (BSA indexed LVH): male >115 g/m2, female >95 g/m2; relative wall thickness ≥0.42; E/e' ≥15 in sinus rhythm (or > 11 in the setting of atrial fibrillation); tricuspid regurgitation velocity >2.8 m/s; Left atrial volume index >34 ml/m2.

  3. GFR ≥ 20 mL/min/1,73 m². 4. NYHA II-IV. 5. On optimal treatment as per physician´s judgement including ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor för HFrEF/HFmrEF, and SGLT2 inhibitors in HFpEF 6. Suboptimal treatment with MRA (defined as: no use or ≤ 25 mg daily 7. And one of following:

  1. Prior hyperkalemia (S-K> 5.0 mmol/L or P-K> 4.8 mmol/L*) during MRA treatment within last 24 months, and current S-K ≤ 5.0 or P-K ≤ 4.8 mmol/L
  2. Current S-K 4.5-5.0 mmol/L or P-K 4.3-4.8 mmol/L, and potential risk of hyperkalemia as indicated by eGFR 30-45 ml/min/1,73 m2

  3. 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). Hyperkalemia is defined as P-K > 4,8 mmol/L or S-K >5,0 mmol/L.

     Exclusion Criteria:

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium Zirconium Cyclosilicate treated; Sodium Zirconium Cyclosilicate	Drug: potassium binder; Sodium Zirconium Cyclosilicate
No Intervention: Control; Usual care as per judgement of treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% of optimizing MRA between Sodium Zirconium Cyclosilicate treated vs control	The efficacy will be assessed by difference in the proportion of patients who may or may not maintain MRA at a dose ≥ 25 mg da	From enrollment to the end of treatment at 6 months
To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimizing MRA in HF, SZC vs control.	The efficacy will be assessed by difference in the proportion of patients who may or may not maintain MRA at a dose ≥ 25 mg da	6 mopnths

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: May 3, 2026
• First Submitted That Met QC Criteria: May 3, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: effect
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: OPRAHF EXT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No