Beneficial effects of Amiloride on progression of Chronic Kidney Disease: A-CKD
- Trial ID
- 2022-500692-31-00
- Sponsor
- Odense University Hospital
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the potential **renoprotective** effects of the diuretic amiloride in patients with **chronic kidney disease** (CKD). The study aims to determine if amiloride can preserve kidney function, reduce cardiovascular morbidity and mortality, and delay the need for renal replacement therapy. This is clinically relevant as it addresses the progression of CKD, a condition that significantly impacts patient quality of life and healthcare resources. The study will investigate whether amiloride's off-target inhibition of urokinase-type plasminogen activator (uPA) contributes to these effects. Additionally, the study will analyze the role of aberrant urine uPA in filtration barrier injury and progressive, complement-mediated kidney tissue injury. The effect of amiloride treatment on tubular complement activation, as measured in urinary samples, and renal interstitial inflammation, assessed through various biomarkers, will also be evaluated.
Participants
The clinical trial focuses on individuals diagnosed with **chronic kidney disease (CKD)**, aiming to evaluate the effects of amiloride treatment on renal function and inflammation. The study population includes both male and female participants, aged 18 years and older, who are not considered part of a vulnerable population. Participants are required to have an estimated glomerular filtration rate (eGFR) between 25 and 60 mL/min/1.73m² and a urine albumin-to-creatinine ratio (UACR) of 300 mg/g or higher at screening. They must be on stable antihypertensive treatment for at least two weeks prior to the study and maintain specific blood pressure parameters. Women of childbearing potential are included only if they test negative for pregnancy at screening and agree to use contraception during the study. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the effects of **amiloride hydrochloride dihydrate** on the progression of **chronic kidney disease (CKD)**. This is a Phase 4, randomized, double-blind, placebo-controlled study. The trial aims to assess the renoprotective effects of amiloride by examining its impact on tubular complement activation and renal interstitial inflammation. The study will involve the administration of amiloride or placebo in tablet form, taken orally, with a maximum daily dose of 10 mg for amiloride and 2 mg for placebo. The maximum treatment period for amiloride is 7 days, while the placebo is administered for 1 day.
The trial is expected to run from September 1, 2023, to July 31, 2025. Participants will be involved in the study for a duration that includes a screening visit, multiple follow-up visits, and an end-of-study visit. The screening visit will confirm eligibility based on criteria such as age, clinical diagnosis of CKD, and stable antihypertensive treatment. Follow-up visits will monitor primary endpoints, including urine C3a, urine soluble C5-9-sTCC/MAC, KIM-1, and NGAL, as well as secondary endpoints like urine albumin/creatinine ratio, urine protein/creatinine ratio, and blood pressure. The end-of-study visit will conclude the participant's involvement and assess the overall outcomes of the treatment.
Participants are expected to remain in the study unless they meet conditions for early termination, such as adverse reactions, non-compliance with the study protocol, or withdrawal of consent. The trial will ensure that all procedures adhere to ethical standards, and participants will be required to provide informed consent before enrollment. The study's design and methodology aim to provide robust data on the potential benefits of amiloride in managing CKD, contributing to the understanding of its therapeutic role in this condition.
Treatment
The clinical trial involves the administration of **MODAMIDE 5 mg, comprimé**, which contains the active substance **amiloride hydrochloride dihydrate**. This experimental medication is presented in the form of a **tablet** and is administered **orally**. The maximum daily dose is set at **10 mg**, with a total maximum dose of **70 mg** over a treatment period of **7 days**. The medication is chemically synthesized and is not a pediatric formulation. The primary objective of the trial is to evaluate the renoprotective effects of amiloride in patients with chronic kidney disease, specifically focusing on its potential to inhibit urokinase-type plasminogen activator and its impact on tubular complement activation and renal interstitial inflammation.
In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is also in the form of a **coated tablet** and is administered **orally**. The maximum daily and total dose for the placebo is **2 tablets**, with a treatment period limited to **1 day**. The placebo is chemically inert and serves to provide a baseline for evaluating the effects of the active treatment. Participant compliance with the dosing schedule is monitored throughout the trial to ensure the integrity of the study results.
Efficacy
Efficacy in the clinical trial titled "Beneficial effects of Amiloride on progression of Chronic Kidney Disease: A-CKD" will be assessed using both primary and secondary endpoints. The primary endpoints include measurements of **urine C3a**, **urine soluble C5-9-sTCC/MAC**, **KIM-1**, and **NGAL**. These biomarkers will be evaluated to determine the effect of amiloride on tubular complement activation and renal interstitial inflammation in patients with chronic kidney disease. Secondary endpoints will focus on the urine albumin/creatinine ratio, urine protein/creatinine ratio, and blood pressure, providing additional insights into the treatment's impact on kidney function and cardiovascular health.
The trial will involve the administration of amiloride, with a maximum daily dose of 10 mg, and a placebo, both administered orally. The maximum treatment period for amiloride is set at 7 days. Efficacy parameters will be collected and analyzed at specified timepoints throughout the study duration, although specific timepoints are not detailed in the provided data. The study aims to evaluate the renoprotective effects of amiloride by inhibiting urokinase-type plasminogen activator and its role in filtration barrier injury and complement-mediated kidney tissue injury. The trial is categorized as a Phase 4 study, focusing on the therapeutic use of an approved medicinal product.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 18 years of age including at the time of signing the informed consent
- A clinical diagnosis of chronic kidney disease and: o eGFR ≥ 25 but < 60mL/min/1.73m2 at screening o UACR of ≥ 300mg/g at screening
- Participants must be on stable antihypertensive treatment 2 weeks before start of study drug and throughout study duration
- Office blood pressure at screening meeting (visit 1) > 110/65mmHg and < 150/90mmHg. If BP > 150/90mmHg at visit 1, screening phase can be prolonged to 12 weeks. # If the office blood pressure varies by approximately ±10 mmHg and is deemed acceptable by the investigator, the participant can be included.
- Capable of giving signed informed consent
- Women with childbearing potential can only be included if a pregnancy test is negative at the screening visit. Moreover, women should be using contraception during the study.
Exclusion Criteria
- Treatment with amiloride alone or use of other types of K-sparing diuretics will be avoided, MR antagonists (Spironolactone, eplerenone, finerenone)
- Evidence of current infection (CRP> 50 and temperature > 38◦C)
- History of unstable or rapidly progressing renal disease (eGFR decreasing > 5ml/min/1.73m2 the last 2 months)
- Severe hepatic insufficiency classified as Child-Pugh C
- Patients on hypertension treatment who is not on stable antihypertensive treatment 2 weeks before start of study drug.
- Pregnancy or breastfeeding participants
- Congestive heart failure NYHA class IV, unstable or acute congestive heart failure.
- Ongoing cancer treatment
- Recent cardiovascular events in a patient: - Less than two months post coronary artery revascularization. - Acute stroke or TIA within two months prior to screening - Acute coronary syndrome within two months prior to screening
- Lactose intolerance
- Patients who, in the judgement of the investigator may be at risk for dehydration.
- Known hypersensitivity to the study treatment (active substance or excipients)
- Known hypersensitivity to resonium
- Addison´s disease
- Gastric bypass operation
- Treatment with immunosuppressive therapy within 6 months prior to screening
- History of organ transplantation
- Participation in other interventional trials
- Plasma potassium > 4.9mmol/L
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Recruiting | 01 Sept 2023 | 40 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PLACEBO | Placebo | — | ORAL USE | 2 | 1 | SUB21402 |
MODAMIDE 5 mg, comprimé | Test | COMPRIMÉ | ORAL | 10 | 7 | PRD9041755 |