Single and Twice-daily Dosing of Ramipril on Renal Function in Chronic Kidney Disease Patients With Reduced Ejection Fraction Heart Failure

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Ramipril
  Ramipril administered either as 10 mg once daily or 5 mg twice daily for 30 days

Первичные конечные точки

• Change in Plasma Renin Activity (PRA) [Срок оценки: 30 days]
• Change in Malondialdehyde (MDA) [Срок оценки: 30 days]
• Change in Interleukin-6 (IL-6) [Срок оценки: 30 days]
• Change in Albuminuria [Срок оценки: 30 days]
• Change in Cystatin C [Срок оценки: 30 days]

Вторичные конечные точки (4)

• Change in Serum Creatinine [Срок оценки: 30 days]
• Change in Estimated Glomerular Filtration Rate (eGFR) [Срок оценки: 30 days]
• Change in Blood Pressure (Systolic and Diastolic) [Срок оценки: 30 days]
• Incidence of Treatment-Related Adverse Events [Срок оценки: 30 days]

Критерии участия

Критерии включения

• 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%)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Индонезия · 1 центр

• UNS Hospital — Kartasura

Публикации

• 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. PMID 32998798
• 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. PMID 34072230
• 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. PMID 35212585
• 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. PMID 38958006
• 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. PMID 28875746
• 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.
• 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. PMID 33238740

Идентификаторы

NCT: NCT07259512 · 041/UN27.46/TA.04.19/KEP/EC/20

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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