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

Phase 2

Completed

• Conditions: Acute Decompensated Heart Failure (ADHF); Chronic Kidney Disease (CKD)
• Interventions: Drug: Sacubitril / Valsartan; Drug: Ramipril (ACE-inhibitor)

• Registration Number: NCT07023016
• Lead Sponsor: National Heart Institute, Egypt

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-01
• Primary Completion: 2025-02-28
• Study Completion: 2025-02-28
• Status Verified: 2025-06
• Study First Submitted: 2025-06-08
• Study First Submitted QC: 2025-06-08
• Study First Posted: 2025-06-15
• Last Update Submitted: 2025-06-17
• Last Update Posted: 2025-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 515

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sacubitril / Valsartan	Sacubitril / Valsartan	-
Ramipril	Ramipril (ACE-inhibitor)	-

Primary Outcome Measures

Name	Time	Method
Difference in mean eGFR (mL/min/1.73m2) between both groups at 12 weeks post-randomization.	12 weeks

Secondary Outcome Measures

Name	Time	Method
Number of patients in each group who develop worsening renal function throughout the study period.	12 weeks	Defined as a 50% increase in the serum creatinine level (mg/dL) from baseline and/or a drop in eGFR by more than 25 ml/min/1.73m2.
Number of events in each group for hyperkalemia throughout the study period.	12 weeks	Defined as a rise in serum potassium level to ≥ 5.5 mEq/L .
Number of events in each group for symptomatic hypotension throughout the study period.	12 weeks	Defined as the subjective sense of dizziness or lightheadedness, blurred, or fading of vision, fainting, fatigue, difficulty concentrating and/or nausea in the presence of a BP of 90/60mmHg or lower.
Number of events in each group for angioedema throughout the study period.	12 weeks	Defined as a swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal tissues.
Difference between NT-proBNP levels (pg/mL) in each group at 12 weeks post-randomization	12 weeks
Difference between LVEF (%) of each group at 12 weeks post-randomization	12 weeks
Difference between uACR levels (gm/mg) in each group at 12 weeks post-randomization.	12 weeks

Trial Locations

Locations (2)

Cairo University Hospitals; 🇪🇬 Cairo, Egypt

National Heart Institute; 🇪🇬 Cairo, Egypt