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

December 2, 2025 updated by: Evi Liliek Wulandari

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Indonesia
    • Central Java
      • Kartasura, Central Java, Indonesia
        • Recruiting
        • UNS Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Once-Daily Ramipril
Participants receive ramipril 10 mg once daily for 30 days
Drug: Ramipril
Ramipril administered either as 10 mg once daily or 5 mg twice daily for 30 days
Other Names:
  • ACE inhibitor
Experimental: Twice-Daily Ramipril
Participants receive ramipril 5 mg twice daily for 30 days
Drug: Ramipril
Ramipril administered either as 10 mg once daily or 5 mg twice daily for 30 days
Other Names:
  • ACE inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Plasma Renin Activity (PRA)
Time Frame: 30 days
Change in plasma renin activity from baseline to day 30.
30 days
Change in Malondialdehyde (MDA)
Time Frame: 30 days
Change in plasma MDA levels as a biomarker of oxidative stress
30 days
Change in Interleukin-6 (IL-6)
Time Frame: 30 days
Change in serum IL-6 levels as a marker of systemic inflammation
30 days
Change in Albuminuria
Time Frame: 30 days
Change in albumin-creatinine ratio (ACR) from baseline to day 30
30 days
Change in Cystatin C
Time Frame: 30 days
Change in serum cystatin C levels as a marker of glomerular filtration
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Creatinine
Time Frame: 30 days
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)
Time Frame: 30 days
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)
Time Frame: 30 days
Change in clinic-measured systolic and diastolic blood pressure from baseline to day 30
30 days
Incidence of Treatment-Related Adverse Events
Time Frame: 30 days
Number and type of adverse events considered related to ramipril during 30 day treatment period (e.g. hyperkalemia), graded by severity
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Evi Liliek Wulandari

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2025

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

January 31, 2026

Study Registration Dates

First Submitted

November 20, 2025

First Submitted That Met QC Criteria

November 20, 2025

First Posted (Estimated)

December 2, 2025

Study Record Updates

Last Update Posted (Actual)

December 10, 2025

Last Update Submitted That Met QC Criteria

December 2, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 041/UN27.46/TA.04.19/KEP/EC/20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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