Comparative Assessment of Efficacy & Safety of Sacubitril/Valsartan Versus Ramipril in Patients With Renal Dysfunction Hospitalized With Acute Decompensated Heart Failure (CAESAR)

National Heart Institute, Egypt

Status and phase

Completed

Phase 3

Phase 2

Conditions

Acute Decompensated Heart Failure (ADHF)

Chronic Kidney Disease (CKD)

Treatments

Drug: Ramipril (ACE-inhibitor)

Drug: Sacubitril / Valsartan

Study type

Interventional

Funder types

Other

Identifiers

NCT07023016

MD-464-2023

Details and patient eligibility

About

Sacubitril/valsartan is an established medication for heart failure. However, data still lags in its use in heart failure patients with chronic kidney disease. Sacubitril/valsartan is manufacturer-labeled for use in patients with eGFR < 30 ml/min/1.73 m2 at an initial dose of 24/26mg twice daily. However, to the best of our knowledge, the concept of sacubitril/valsartan or ACEi in patients with chronic kidney disease & presenting with decompensated heart failure has not yet been explored fully.

Enrollment

515 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: All the following should be met:

Acute decompensated heart failure (ADHF)
Left ventricular ejection fraction (LVEF) below 40%
Renal dysfunction; defined as eGFR of 30mL/min/1.73m2 to less than 60mL/min/1.73m2 in relation to the level of urinary albumin/creatinine ratio (uACR) based on the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for the evaluation and management of CKD.
A minimum blood pressure (BP) ≥ 105/60 mmHg.
Independent of any inotropic or vasopressor support in the previous 24 hours before inclusion and randomization.
No more than 72 hours had passed since admission to the heart failure unit.
Patients should have had a New York Heart Association (NYHA) functional class II-IV, in addition to symptoms of volume overload at the time of presentation to the emergency room.

Exclusion Criteria:

Patients who were on sacubitril/valsartan or ACEI/ angiotensin receptor blocker (ARB) prior to inclusion.
Patients with AKI on presentation OR in the last 3 months OR had ≥ 2 hospital admissions in the last 12 months for AKI.
History of known or suspected hypersensitivity, contraindications, or intolerance to any of the study drugs including ACEI, ARB or sacubitril (neprilysin inhibitor).
Requirement for double treatment with both ACEI and ARB.
Serum potassium (K+) level ≥ 5.0 mmol/L at randomization.
A recent major adverse cardiovascular/cerebrovascular event within 1 month (acute coronary syndrome, stroke, transient ischemic attack, etc.).
Patients with hemodynamically significant primary valvular lesion.
Known hepatic impairment with a model for end-stage liver disease (MELD) score >10. 23
History of malignancy of any organ system within the past year with a life expectancy < 1 year.