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

NCT07259512 | Recruiting Phase 4

• 1 other identifier: 041/UN27.46/TA.04.19/KEP/EC/20
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease; Heart Failure With Reduced Ejection Fraction (HFrEF)

Keywords

Chronic Kidney Disease; HFrEF; Ramipril

Outcome Measures

Primary Outcomes (5)

• 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

Secondary Outcomes (4)

• 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

Study Arms (2)

Once-Daily Ramipril

EXPERIMENTAL

Participants receive ramipril 10 mg once daily for 30 days

Drug: Ramipril

Twice-Daily Ramipril

EXPERIMENTAL

Participants receive ramipril 5 mg twice daily for 30 days

Drug: Ramipril

Interventions

Ramipril DRUG

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

Also known as: ACE inhibitor

Once-Daily Ramipril; Twice-Daily Ramipril

Eligibility Criteria

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

You may qualify if:

• 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%)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Evi Liliek Wulandari: lead

Study Sites (1)

UNS Hospital

Kartasura, Central Java, Indonesia

RECRUITING

Related Publications (7)

• 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 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.

  PMID: 34072230 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.

  PMID: 35212585 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.

  PMID: 38958006 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.

  PMID: 28875746 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.

  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.

  PMID: 33238740 RESULT

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

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

Central Study Contacts

Evi L Wulandari, MD., Internist

CONTACT

(+62)821-3587-2749; evililiek@staff.uns.ac.id

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Consultant Internist (Internal Medicine Specialist)

Model Details: 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.

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: June 30, 2025
• Primary Completion: December 31, 2025
• Study Completion: January 31, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

ID (1)