Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.

This is a Phase I, Multicentre study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] during 28 days in Patients with HFmrEF or HFpEF and eGFR in the range of ≥40 and ≤70 mL/min/1.73m2.

Inclusion Criteria:

• Symptoms and signs consistent with a diagnosis of heart failure (HF)
• Left ventricular ejection fraction (LVEF) ≥40% by transthoracic echocardiography within the past 12 months
• Plasma NT-proBNP level ≥125 pg/ml (≥ 600pg/mL if patient has persistent or permanent atrial fibrillation, atrial flutter, or atrial tachycardia)
• Estimated glomerular filtration rate (eGFR) ≥40 and ≤70ml/min/1.73m2 (by CKD-EPI formula).
• Baseline serum potassium (sK+) level ≥3.5 and ≤4.8mmol/l.
• Stable doses of the following medications at baseline for at least 4 weeks prior to randomisation:

Angiotensin receptor blocker (ARB) or Angiotensin converting enzyme inhibitor (ACEi) Loop diuretic (up to a 120mg furosemide dose or equivalent

Exclusion Criteria:

• Patients with documented LVEF <40% at any time (i.e. patients with previously impaired LVEF that has now improved are not permitted).
• Patients experiencing acute decompensation of heart failure requiring hospital admission or escalation in therapy.
• Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy in judgment of Investigator).
• Hyponatraemia, defined as serum Na+ <135 mmol/L at the time of enrollment.
• Persistent resting sinus tachycardia >110 bpm or sinus bradycardia <45bpm.
• Systolic blood pressure (BP) <110mmHg or >180mmHg.
• Diastolic BP <60 mmHg or >100 mmHg.
• Patients previously intolerant to MRA (e.g. spironolactone or eplerenone) for any reason.
• Medical conditions associated with development of hyperkalaemia (e.g. Addison's disease).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN).
• Patients who have been taking an MR antagonist within 1 month prior to randomization.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.