Comparative Effects of Single Versus Twice-Daily Ramipril Dosing on Renal Function in Patients With Chronic Kidney Disease and Heart Failure With Reduced Ejection Fraction: Evaluation of Plasma Renin Activity, Malondialdehyde, Interleukin-6, Albuminuria, and Cystatin C
Overview
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Evi Liliek Wulandari
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Change in Plasma Renin Activity (PRA)
Overview
Brief Summary
This study compares the effects of once-daily versus twice-daily ramipril dosing on renal function in chronic kidney disease (CKD) patients with heart failure with reduced ejection fraction (HFrEF). Outcomes include changes in plasma renin activity, malondialdehyde, interleukin-6, albuminuria, and cystatin C after 30 days of therapy.
Detailed Description
Chronic kidney disease (CKD) frequently coexists with heart failure with reduced ejection fraction (HFrEF), characterized by neurohormonal activation, inflammation, oxidative stress, and progressive renal deterioration. Activation of the renin-angiotensin-aldosterone system (RAAS) contributes significantly to both renal and cardiac dysfunction. Ramipril, an ACE inhibitor, is widely recommended for CKD with albuminuria and HFrEF. However, discrepancies exist in guidelines regarding once-daily versus twice-daily administration. These differences may influence RAAS suppression effectiveness and patient adherence.
This randomized, double-blind, parallel assignment clinical trial investigates the impact of once-daily (10 mg every 24 hours) versus twice-daily (5 mg every 12 hours) ramipril dosing on renal biomarkers in CKD patients with HFrEF. Outcomes include plasma renin activity (PRA), malondialdehyde (MDA), interleukin-6 (IL-6), albuminuria, and cystatin C measured over a 30-day treatment period. The study aims to provide scientific evidence to support optimal ramipril dosing strategies that improve renal outcomes among patients with CKD and reduced ejection fraction heart failure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Female or Male with age \>18 years old
- •Patients with a diagnosis of CKD stage 3-5 non-dialysis with low ejection fraction heart failure (ejection fraction \< 40%)
Exclusion Criteria
- •Receiving hemodialysis therapy
- •History of intolerance to ACE inhibitors
- •Refractory hyperkalemia
- •Pregnancy
- •History of angioedema to ACE inhibitors
- •Receiving sacubitril-valsartan therapy
- •Receiving ARB therapy
- •Hypotension with blood pressure \<90/60, or patients in shock.
Arms & Interventions
Once-Daily Ramipril
Participants receive ramipril 10 mg once daily for 30 days
Intervention: Ramipril (Drug)
Twice-Daily Ramipril
Participants receive ramipril 5 mg twice daily for 30 days
Intervention: Ramipril (Drug)
Outcomes
Primary Outcomes
Change in Plasma Renin Activity (PRA)
Time Frame: 30 days
Change in plasma renin activity from baseline to day 30.
Change in Malondialdehyde (MDA)
Time Frame: 30 days
Change in plasma MDA levels as a biomarker of oxidative stress
Change in Interleukin-6 (IL-6)
Time Frame: 30 days
Change in serum IL-6 levels as a marker of systemic inflammation
Change in Albuminuria
Time Frame: 30 days
Change in albumin-creatinine ratio (ACR) from baseline to day 30
Change in Cystatin C
Time Frame: 30 days
Change in serum cystatin C levels as a marker of glomerular filtration
Secondary Outcomes
- Change in Serum Creatinine(30 days)
- Change in Estimated Glomerular Filtration Rate (eGFR)(30 days)
- Change in Blood Pressure (Systolic and Diastolic)(30 days)
- Incidence of Treatment-Related Adverse Events(30 days)
Investigators
Evi Liliek Wulandari
Principal Investigator, Consultant Internist (Internal Medicine Specialist)
Universitas Sebelas Maret