Acute Decompensated Heart Failure (ADHF), Chronic Kidney Disease (CKD)
Conditions
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.
Interventions
Patients will receive sacubitril/valsartan at an initial dose of 24/26 mg Bid.
Patients will receive ramipril at an initial dose of 2.5 mg Bid.
Sponsors
Cairo University
National Heart Institute, Egypt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in mean eGFR (mL/min/1.73m2) between both groups at 12 weeks post-randomization. | 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Other
| Measure | Time frame |
|---|---|
| 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 |
Countries
Egypt
Outcome results
None listed