A study to evaluate 12 weeks of treatment with the study drug combination of AZD9977 and dapagliflozin when given to participants with heart failure and kidney disease (MIRACLE study)
- Conditions
- Health Condition 1: N183- Chronic kidney disease, stage 3 (moderate)Health Condition 2: N184- Chronic kidney disease, stage 4 (severe)Health Condition 3: I501- Left ventricular failure, unspecified
- Registration Number
- CTRI/2023/02/049538
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
Participants are included in the study if any of the following criteria apply
1. 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.
2. Left ventricular ejection fraction <60% documented by the most recent echocardiogram or cardiac magnetic resonance imaging within the last 12 months prior to screening.
3. Stable background treatment for HF, hypertension, diabetes mellitus or renal disease according to guidelines.
4. N-terminal-pro-brain natriuretic peptide (NT proBNP) >=300 pg/mL for participants with sinus rhythm at screening; and NT proBNP >=600 pg/mL for participants with atrial fibrillation/flutter at screening.
5. The eGFR greater than or equal to 30 and less than or equal to 60 mL/min/1.73square (by CKD- EPI formula) and UACR >=30 mg/g (3 mg/mmol) and <3000 mg/g (300 mg/mmol)
6. Body mass index less than 40 kg/m square
7. Serum/plasma K+ level >= 3.5 and < 5.0 mmol/L within 10 days prior to randomization
8. Serum/ plasma Na+ level within normal reference values within 10 days prior to randomization
9. Systolic blood pressure should be at protocol defined range at randomization (Visit 3), with no change to antihypertensive treatments in previous 3 weeks.
10. Male or female of non-childbearing potential.
11. All participants must follow protocol defined contraceptives procedures.
Participants are excluded from the study if any of the following criteria apply
1. 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
2. Participants with currently decompensated HF requiring hospitalization for optimization of HF treatment and are not on stable HF therapy at the time of enrollment
3. HF due to cardiomyopathies
4. High output HF e.g., due to hyperthyroidism or Pagets disease.
5. HF due to pericardial disease, congenital heart disease or clinically significant uncorrected primary cardiac valvular disease or planned cardiac valve repair or replacement.
6. Participants with uncontrolled diabetes mellitus (Glycated hemoglobin >10%).
7. Participants with Type 1 diabetes mellitus.
8. Intermittent or persistent 2nd or 3rd degree atrioventricular block, sinus node dysfunction with clinically significant bradycardia or sinus pauses, not treated with a pacemaker.
9. History of any life-threatening cardiac dysrhythmia or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter
10. 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.
11. 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 or is planned to undergo any cardiovascular surgery during the study.
12. Heart transplantation or left ventricular assist device at any time or if these are planned
13. Kidney or any organ transplantation or if these are planned.
14. Medical conditions associated with development of hyperkalaemia (Addisons disease).
15. History or ongoing allergy/hypersensitivity, to sodium-glucose co-transporter-2 inhibitor (SGLT2i e.g., dapagliflozin, empagliflozin).
16. Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to randomisation.
17. 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.
18. Participants with newly detected pathological laboratory values or an ongoing disease condition
19. 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
20. Previous randomization in the present study
21. Prior medical treatment with an mineralocorticoid receptor antagonist where the medication was taken within 90 days prior to screening
22. 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 Evaluating the effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACRTimepoint: Baseline (Day 1) until Week 12 (Day 85)
- Secondary Outcome Measures
Name Time Method Assessment of the dose-response relationship of dapagliflozin (10 mg) alone and 3 doses of AZD9977 (A, B, or C) combined with dapagliflozin (10 mg) on UACR.Timepoint: Baseline (Day 1) until Week 12 (Day 85)