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

NCT07023016 | Completed Phase 2 DMC

• 1 other identifier: MD-464-2023
• Study Type: interventional
• Target: 515
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Decompensated Heart Failure (ADHF); Chronic Kidney Disease (CKD)

Outcome Measures

Primary Outcomes (1)

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

  12 weeks

Secondary Outcomes (7)

• Number of patients in each group who develop worsening renal function throughout the study period.

  12 weeks

• Number of events in each group for hyperkalemia throughout the study period.

  12 weeks

• Number of events in each group for symptomatic hypotension throughout the study period.

  12 weeks

• Number of events in each group for angioedema throughout the study period.

  12 weeks

• Difference between uACR levels (gm/mg) in each group at 12 weeks post-randomization.

  12 weeks

Other Outcomes (2)

• HF rehospitalization: this will include the total number of patients in each group who will require hospital re-admission for ADHF.

  12 weeks

• All-cause mortality: this will include the total number of deaths in each group regardless of the underlying cause.

  12 weeks

Study Arms (2)

Sacubitril / Valsartan

EXPERIMENTAL

Drug: Sacubitril / Valsartan

Ramipril

ACTIVE COMPARATOR

Drug: Ramipril (ACE-inhibitor)

Interventions

Sacubitril / Valsartan DRUG

Patients will receive sacubitril/valsartan at an initial dose of 24/26 mg Bid.

Sacubitril / Valsartan

Ramipril (ACE-inhibitor) DRUG

Patients will receive ramipril at an initial dose of 2.5 mg Bid.

Ramipril

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Heart Institute, Egypt: lead
• Cairo University: collaborator

Study Sites (2)

Cairo University Hospitals

Cairo, Egypt

Location

National Heart Institute

Cairo, Egypt

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

sacubitril and valsartan sodium hydrate drug combination; Ramipril; Angiotensin-Converting Enzyme Inhibitors

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Hesham Salah Eldin Taha, MD

  Cairo University

  STUDY DIRECTOR

• Omar Younis, Msc

  National Heart Institiute, Cairo - Egypt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiology Researcher

Study Record Dates

• First Submitted: June 8, 2025
• First Posted: June 15, 2025
• Study Start: November 1, 2023
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

EG (2)