OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure (OPRA-HF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Aug 2021 → 20 Jan 2026

Decision date (initial)

2024-08-14

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-511502-24-02

EudraCT number

2020-005176-35

ClinicalTrials.gov

NCT04789239

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing mineralocorticoid receptor antagonists (MRA) in symptomatic patients with heart failure with reduced ejection fraction (HFrEF)

Secondary objectives 4

1. To determine the efficacy of SZC when com-pared to placebo in maintaining achieved MRA-dose after run-in period, SZC vs Placebo;
2. To determine the impact of MRA-optimization by SZC in quality of life (QoL)-parameters, SZC vs Placebo ;
3. To determine the estimated treatment persisten-cy of highest tolerable dose (25-50 mg daily) of MRA, SZC vs Placebo;
4. To evaluate the safety and tolerability of SZC when compared to placebo as assessed by differ-ences in percent (%) between the two groups in pre-specified safety endpoints (occurring at any point during the study)

Conditions and MedDRA coding

High-risk hyperkalemia

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Obtain signed informed consent prior to any study specific procedures.
2. >18 yrs, irrespective of sex.
3. LVEF ≤ 40%, with echocardiography within last 2 years including those with recovered EF later on
4. NYHA II-IV.
5. Stable heart failure as judged by local Investigator. Patients may be enrolled as an outpatient or in-hospital at, or close to, the time of hospital discharge.
6. On optimal treatment including ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor as per physician´s judgement.
7. Suboptimal treatment with MRA (defined as: no use or ≤ 25 mg daily).
8. AND one of followings: a. 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 b. 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 (modi-fied MDRD formula) c. Current S-K 5.1-5.9 mmol/L or P-K 4.9-5.7 mmol/L

Exclusion criteria 13

1. Symptomatic hypotension (< 90/60 mmHg)
2. eGFR < 30 ‎ml/min/1,73 m2 (modified MDRD formula)
3. HF due to restrictive cardiomyopathy, hypertrophic (obstructive) cardiomy-opathy or primary valvular disease
4. Current/recent (within 3 months) hospitalization due to myocardial infarc-tion, unstable angina pectoris, coronary revascularization (percutaneous cor-onary intervention or coronary artery bypass grafting), or other interventions (valvular repair/replacement, cardiac transplantation, or implantation of a ventricular assistance device)
5. Ongoing or planned dialysis
6. Prior history of hypersensitivity (other than hyperkalemia) to MRA or SZC
7. Advanced malignancy requiring treatment
8. History of QT prolongation associated with other medication which required discontinuation of that medication
9. Congenital long QT syndrome
10. Symptomatic and uncontrolled atrial fibrillation despite treatment, or asymp-tomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
11. QTc(f) > 550 msec
12. Currently pregnant (confirmed with positive pregnancy test) or planned pregnancy or breast-feeding
13. Can not sign informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimizing MRA in HFrEF, SZC vs Placebo. The efficacy will be assessed by difference in the proportion of patients who may or may not maintain MRA at a dose ≥ 25 mg daily or a dose increase by 25 mg daily and K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hy-perkalemia at any point during the randomization phase.

Secondary endpoints 4

1. To determine the efficacy of SZC when compared to placebo in maintaining achieved MRA-dose after run-in period, SZC vs Placebo.
2. To determine the impact of MRA-optimization by SZC in QoL-parameters, SZC vs Place-bo.
3. To determine the estimated treatment persistency of highest tolerable dose (25-50 mg dai-ly) of MRA between SZC vs Placebo.
4. To evaluate the safety and tolerability of SZC when compared to placebo as assessed by differences in percent (%) between the two groups in pre-specified safety endpoints (oc-curring at any point during the study)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Michael

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Michael

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications