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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Once-Daily Ramipril | Experimental | Participants receive ramipril 10 mg once daily for 30 days |
|
| Twice-Daily Ramipril | Experimental | Participants receive ramipril 5 mg twice daily for 30 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ramipril | Drug | Ramipril administered either as 10 mg once daily or 5 mg twice daily for 30 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma Renin Activity (PRA) | Change in plasma renin activity from baseline to day 30. | 30 days |
| Change in Malondialdehyde (MDA) | Change in plasma MDA levels as a biomarker of oxidative stress | 30 days |
| Change in Interleukin-6 (IL-6) | Change in serum IL-6 levels as a marker of systemic inflammation | 30 days |
| Change in Albuminuria | Change in albumin-creatinine ratio (ACR) from baseline to day 30 | 30 days |
| Change in Cystatin C | Change in serum cystatin C levels as a marker of glomerular filtration | 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Serum Creatinine | Change in serum creatinine concentration from baseline to day 30, measured by standard hospital laboratory methods | 30 days |
| Change in Estimated Glomerular Filtration Rate (eGFR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Evi L Wulandari, MD., Internist | Contact | (+62)821-3587-2749 | evililiek@staff.uns.ac.id |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNS Hospital | Recruiting | Kartasura | Central Java | Indonesia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32998798 | Result | Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020 Oct;98(4S):S1-S115. doi: 10.1016/j.kint.2020.06.019. No abstract available. | |
| 34072230 | Result | Ariton DM, Jimenez-Balado J, Maisterra O, Pujadas F, Soler MJ, Delgado P. Diabetes, Albuminuria and the Kidney-Brain Axis. J Clin Med. 2021 May 27;10(11):2364. doi: 10.3390/jcm10112364. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jun 30, 2025 |
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Participants are randomly assigned in parallel to one of two treatment groups: once-daily ramipril (10 mg every 24 hours) or twice-daily ramipril (5 mg every 12 hours). Each participant remains in the same assigned arm for the entire 30-day treatment period, and outcomes are assessed at baseline and day 30.
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Change in estimated glomerular filtration rate (eGFR) from baseline to day 30, calculated using the CKD-EPI equation
| 30 days |
| Change in Blood Pressure (Systolic and Diastolic) | Change in clinic-measured systolic and diastolic blood pressure from baseline to day 30 | 30 days |
| Incidence of Treatment-Related Adverse Events | Number and type of adverse events considered related to ramipril during 30 day treatment period (e.g. hyperkalemia), graded by severity | 30 days |
| 35212585 | Result | Kreiner FF, Kraaijenhof JM, von Herrath M, Hovingh GKK, von Scholten BJ. Interleukin 6 in diabetes, chronic kidney disease, and cardiovascular disease: mechanisms and therapeutic perspectives. Expert Rev Clin Immunol. 2022 Apr;18(4):377-389. doi: 10.1080/1744666X.2022.2045952. Epub 2022 Mar 1. |
| 38958006 | Result | Jakopin E, Knehtl M, Hojs NV, Bevc S, Piko N, Hojs R, Ekart R. Treatment of acute kidney injury with continuous renal replacement therapy and cytokine adsorber (CytoSorb(R)) in critically ill patients with COVID-19. Ther Apher Dial. 2024 Dec;28(6):941-950. doi: 10.1111/1744-9987.14182. Epub 2024 Jul 3. |
| 28875746 | Result | Nijst P, Verbrugge FH, Martens P, Bertrand PB, Dupont M, Francis GS, Tang WW, Mullens W. Plasma renin activity in patients with heart failure and reduced ejection fraction on optimal medical therapy. J Renin Angiotensin Aldosterone Syst. 2017 Jul-Sep;18(3):1470320317729919. doi: 10.1177/1470320317729919. |
| Result | Arifiyanto, A. Y., Dwi Laksono, A., Chalidyanto, D., Taniasari, N., & Kusumaningtyas, W. (2021). Factors Related to the Prevalenceof Chronic Kidney Disease in Indonesia:An Ecological Study. Indian Journal of Forensic Medicine & Toxicology, 15(3), 1867-1873. |
| 33238740 | Result | Tedeschi A, Agostoni P, Pezzuto B, Corra' U, Scrutinio D, La Gioia R, Raimondo R, Passantino A, Piepoli MF. Role of comorbidities in heart failure prognosis Part 2: Chronic kidney disease, elevated serum uric acid. Eur J Prev Cardiol. 2020 Dec;27(2_suppl):35-45. doi: 10.1177/2047487320957793. |
| Dec 2, 2025 |
| Prot_SAP_ICF_001.pdf |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D017257 | Ramipril |
| D000806 | Angiotensin-Converting Enzyme Inhibitors |
| ID | Term |
|---|---|
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011480 | Protease Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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