Clinical trial NCT07023016: Comparative Assessment of Efficacy & Safety of Sacubitril/Valsartan Versus Ramipril in Patients With Renal Dysfunction Hospitalized With Acute Decompensated Heart Failure
Official title: Comparative Assessment of Efficacy & Safety of Sacubitril/Valsartan Versus Ramipril in Patients With Renal Dysfunction Hospitalized With Acute Decompensated Heart Failure - CAESAR (a Randomized Controlled Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Decompensated Heart Failure (ADHF)
Chronic Kidney Disease (CKD)
Lead sponsor: National Heart Institute, Egypt
Sponsor class: OTHER_GOV
Collaborators: name: Cairo University Hospitals
First posted: 2025-06-15
Enrollment: 515
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Difference in mean eGFR (mL/min/1.73m2) between both groups at 12 weeks post-randomization.
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of patients in each group who develop worsening renal function throughout the study period.
timeFrame: 12 weeks
measure: Number of patients in each group who develop hyperkalemia throughout the study period.
timeFrame: 12 weeks
measure: Number of patients in each group who develop symptomatic hypotension throughout the study period.
timeFrame: 12 weeks
measure: Number of patients in each group who develop angioedema throughout the study period.
timeFrame: 12 weeks
measure: Difference between uACR levels (gm/mg) in each group at 12 weeks post-randomization.
timeFrame: 12 weeks
measure: Difference between NT-proBNP levels (pg/mL) in each group at 12 weeks post-randomization
timeFrame: 12 weeks
measure: Difference between LVEF (%) of each group at 12 weeks post-randomization
timeFrame: 12 weeks
Other outcomes:
measure: HF rehospitalization: this will include the total number of patients in each group who will require hospital re-admission for ADHF.
timeFrame: 12 weeks
measure: All-cause mortality: this will include the total number of deaths in each group regardless of the underlying cause.
timeFrame: 12 weeks
Locations:
city: Cairo
country: Egypt
facility: Cairo University Hospitals
city: Cairo
country: Egypt
facility: National Heart Institute
Study officials:
affiliation: Cairo University Hospitals
name: Hesham Salah Eldin Taha, MD
role: STUDY_DIRECTOR
affiliation: National Heart Institiute, Cairo - Egypt
name: Omar Younis, Msc
role: PRINCIPAL_INVESTIGATOR
References: