Efficacy, safety and tolerability of AZD9977 and dapagliflozin in patients with heart failure and chronic kidney disease
- Conditions
- Heart Failure, Chronic Kidney Disease
- Registration Number
- JPRN-jRCT2031200272
- Lead Sponsor
- Hibi Kazushige
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
Documented diagnosis of stable symptomatic HF (New York Heart Association class II-III) at screening, and a medical history of typical symptoms and signs of HF in those who are currently receiving loop diuretic treatment
- Left ventricular ejection fraction <60% documented by the most recent echocardiogram or cardiac magnetic resonance imaging within the last 12 months prior to screening.
- Stable background treatment for HF, hypertension, diabetes mellitus or renal disease according to guidelines
- N-terminal-pro-brain natriuretic peptide (NT proBNP) 300 pg/mL or more for participants with sinus rhythm at screening; and NT proBNP 600 pg/mL or more for participants with atrial fibrillation/flutter at screening
- The eGFR 30 or more and 60 mL/min/1.73^2 (by CKD- EPI formula) or less and UACR >30 mg/g (3 mg/mmol) or more and <3000 mg/g (300 mg/mmol)
- Serum/plasma K+ level 3.5 or more and <5.0 mmol/L within 10 days prior to randomization
- Serum/ plasma Na+ level within normal reference values within 7 days prior to randomization
- Systolic blood pressure should be at protocol defined range at randomization (Visit 3), with no change to antihypertensive treatments in previous 3 weeks
- Body mass index less than 40 kg/m^2
- Male or female of non-childbearing potential
- All participants must follow protocol defined contraceptives procedures
- Primary glomerulopathy, vasculitic renal disease, prior dialysis or unstable rapidly progressing renal disease, autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasm antibody -associated vasculitis
- Participants with currently decompensated HF requiring hospitalization for optimization of HF treatment and are not on stable HF therapy at the time of enrollment
- HF due to cardiomyopathies
- High output HF (e.g., due to hyperthyroidism or Paget's disease)
- HF due to pericardial disease, congenital heart disease or clinically significant uncorrected primary cardiac valvular disease or planned cardiac valve repair/replacement
- Participants with uncontrolled diabetes mellitus (Glycated hemoglobin >10%)
- Participants with Type 1 diabetes mellitus
- Intermittent or persistent 2nd or 3rd degree atrioventricular block, sinus node dysfunction with clinically significant bradycardia or sinus pauses, not treated with a pacemaker
- History of any life-threatening cardiac dysrhythmia or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter
- Acute coronary syndrome and/or elective/non-elective percutaneous cardiac interventions (within 3 months) prior to randomisation or is planned to undergo any of these procedures during the study
- Any major cardiovascular (eg, open chest, coronary artery bypass grafting or valvular repair/replacement) or major non-cardiovascular surgery within 3 months prior to randomisation (Visit 3) or is planned to undergo any cardiovascular surgery during the study
- Heart transplantation or left ventricular assist device at any time or if these are planned
- Kidney or any organ transplantation or if these are planned
- Medical conditions associated with development of hyperkalaemia (Addison's disease )
- History or ongoing allergy/hypersensitivity, to sodium-glucose co-transporter-2 inhibitor (SGLT2i e.g., dapagliflozin, empagliflozin)
- Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to randomisation
- Hepatic disease, including hepatitis and/or hepatic impairment (Child-Pugh class A-C), and aspartate aminotransferase or alanine transaminase or total bilirubin should be in protocol defined range at time of screening and/ or within 7 days prior to randomization
- Participants with newly detected pathological laboratory values or an ongoing disease condition
- If the participants clinical signs and symptoms consistent with COVID-19, and has been previously hospitalized with COVID-19 infection and did not fully recover their previous health status
- Previous randomization in the present study
- Prior medical treatment with an mineralocorticoid receptor antagonist where the medication was taken within 90 days prior to screening
- Current or prior treatment within 6 months prior to screening with cytotoxic therapy, immunosuppressive therapy, or other immunotherapy
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percent change from baseline in UACR at 12 weeks [ Time Frame: Baseline (Day 1) until Week 12 (Day 85) ]<br>Evaluating the effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACR.
- Secondary Outcome Measures
Name Time Method