Beneficial effects of Amiloride on progression of Chronic Kidney Disease: A-CKA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

10 Oct 2024 → ongoing

Decision date (initial)

2023-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The aim is to preserve kidney function, avoid excess cardiovascular morbidity and mortality and renal replacement therapy in chronic kidney disease. The study objectives are to test if the diuretic amiloride exerts unrecognized renoprotective effects by off-target inhibition of urokinase-type plasminogen activator, uPA. Moreover, to analyze the role of aberrant urine urokinase-type plasminogen activator for filtration barrier injury and progressive, complement-mediated kidney tissue injury
The objective it to evaluate the effect of amiloride treatment in patients with chronic kidney disease in regard to tubular complement activation measured in urinary samples and evaluate renal interstitial inflammation (by various biomarkers). Additionally, an inhibitory effect on proteases may protect the kidney by reducing the growth potential of bacterial proliferation

Conditions and MedDRA coding

Chronic kidney disease (CKD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant must be 18 years of age including at the time of signing the informed consent
2. 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
3. Participants must be on stable antihypertensive treatment 2 weeks before start of study drug and throughout study duration
4. 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.
5. Capable of giving signed informed consent
6. 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 19

1. Treatment with amiloride alone or use of other types of K-sparing diuretics will be avoided, MR antagonists (Spironolactone, eplerenone, finerenone)
2. Evidence of current infection (CRP> 50 and temperature > 38◦C)
3. History of unstable or rapidly progressing renal disease (eGFR decreasing > 5ml/min/1.73m2 the last 2 months)
4. Severe hepatic insufficiency classified as Child-Pugh C
5. Patients on hypertension treatment who is not on stable antihypertensive treatment 2 weeks before start of study drug.
6. Pregnancy or breastfeeding participants
7. Congestive heart failure NYHA class IV, unstable or acute congestive heart failure.
8. Ongoing cancer treatment
9. 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
10. Lactose intolerance
11. Patients who, in the judgement of the investigator may be at risk for dehydration.
12. Known hypersensitivity to the study treatment (active substance or excipients)
13. Known hypersensitivity to resonium
14. Addison´s disease
15. Gastric bypass operation
16. Treatment with immunosuppressive therapy within 6 months prior to screening
17. History of organ transplantation
18. Participation in other interventional trials
19. Plasma potassium > 4.9mmol/L

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Urine C3a
2. Urine soluble C5-9-sTCC/MAC
3. KIM-1
4. NGAL

Secondary endpoints 3

1. Urine albumin/creatinine ratio
2. Urine protein/creatinine ratio
3. Blood pressure

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Gitte Rye Hinrichs

Public contact point

Organisation

Odense University Hospital

Contact name

Gitte Rye Hinrichs

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications