Randomized controlled trial evaluating the impact of mineralocorticoid receptor blockade by eplerenone on echocardiographic abnormalities among kidney graft recipient under calcineurin inhibitors. KT-CANOPY : Cardiac improvement by eplerenone among patients under cyclosporine or tacrolimus for kidney transplantation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHRU De Nancy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-03-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health (PHRC IR 2019)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the impact of 36 weeks administration of eplerenone on a hierarchical composite endpoint including major cardiovascular events and cardiac structural changes in kidney transplant recipients for more than one year, receiving calcineurin inhibitors.

Secondary objectives 9

1. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on left ventricular systolic and diastolic cardiac function.
2. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on peripheral blood pressure
3. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on natriuretic peptides
4. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on biomarkers of fibrosis
5. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on endothelial dysfunction
6. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on graft function
7. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on the risk of severe hyperkalaemia
8. To assess the impact of 36 weeks administration of eplerenone in kidney transplant recipients for more than one year, receiving calcineurin inhibitors on the risk of acute renal failure
9. Evaluate the association of biological characteristics with echocardiographic characteristics (in both randomized and non-randomized patients).

Conditions and MedDRA coding

kidney transplantation

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Men or women ≥ 18 years of age.
2. Person who has undergone a prior clinical examination suitable for the clinical trial.
3. Renal transplant patient for at least one year.
4. Patient on long-term ciclosporin or tacrolimus therapy.
5. Patient with a clinical and biological situation stable for at least three months: no change in treatment with a potential impact on blood pressure for 3 months (excluding immunosuppressive therapy) and no acute graft rejection diagnosed within 3 months
6. Patient with a GFR estimated according to the CKD-EPI formula ≥40ml/min/1.73m2 less than one month old.
7. Patient with peripheral SBP≥110mmHg, regardless of whether or not antihypertensive treatment (including ACE inhibitor or sartan) is being used.
8. With the following echocardiographic abnormalities on trans-thoracic echocardiography performed at inclusion: - Indexed LV mass > 88 g/m2 in women or > 102 g/m2 in men, - And/or Left atrial volume > 34 ml/m2.
9. Patient signed informed consent.
10. Patient affiliated to a social security scheme or beneficiary of such a scheme.

Exclusion criteria 25

1. Patient transplanted more than 5 years.
2. Patient in permanent atrial fibrillation.
3. Patient with valve disease grade 3 or higher.
4. A patient whose risk of mortality is considered to be very high in the following year.
5. Patients with documented kalaemia ≥ 5mmol/L in the month before or on long-term potassium chelating resins.
6. Blood bicarbonate level < 20mmol/L with or without documented supplementation in the month before.
7. Patient under mineralocorticoid receptor antagonist or with formal indication to receive this treatment.
8. Patient receiving another potassium-sparing diuretic.
9. Patients receiving a combination of ACE inhibitors and sartan.
10. Patients treated with digoxin.
11. Left ventricular ejection fraction <40% on echocardiography at inclusion.
12. Planned ligature of the arteriovenous fistula in the coming year.
13. Known hypersensitivity or allergy to eplerenone and its excipients.
14. Patients with severe hepatic impairment (Child-Pugh class C).
15. Patient treated with a potent CYP3A4 inhibitor (e.g. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone).
16. Patients with known galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome.
17. Patients with a contraindication to Kayexalate: history of hypersensitivity to polystyrene sulphonate resins, obstructive intestinal pathology or laxative treatment with sorbitol.
18. A woman of childbearing age without an effective contraceptive device : A woman is considered to be of childbearing age, i.e., fertile, from the onset of her first menstruation until she becomes menopausal, unless she is permanently sterile. An effective contraceptive method is considered to be: estrogen-progestogen hormonal contraception that inhibits ovulation, administered orally, intravaginally, or transdermally; or progestogen-only hormonal contraception that inhibits ovulation, administered orally, by injection, or implant; or intrauterine device (IUD) or hormonal IUD; or tubal ligation; or male partner with vasectomy; or sexual abstinence.
19. Women wishing to become pregnant within 12 months.
20. Patient taking part in other therapeutic interventional research.
21. Pregnant woman, parturient or breast-feeding mother
22. Minor child (not emancipated)
23. An adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
24. Persons deprived of their liberty by a judicial or administrative decision.
25. Patient unable to express consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hierarchized composite criterion evaluated at 36 weeks (win ratio method), including in order of priority: 1/ Death or hospitalization for heart failure or acute coronary syndrome, 2/ Variation in indexed left ventricular mass (LVMi) (with a precision of 5 g/m² allowing patients with a difference in variation LVMi between randomization and 36 weeks of less than 5 g/m² to be considered as tied), 3/Variation in indexed left atrial volume.

Secondary endpoints 9

1. Evolution o f parameters of systolic function (LVEF, strain), remodeling (left ventricular and atrial volumes) and filling pressures (E/e', deceleration time, PAPs) at 36 weeks
2. Evolution of peripheral systolic blood pressure (pSBP in mmHg), peripheral diastolic blood pressure (pDBP in mmHg), peripheral pulse pressure (pPP in mmHg) at 36 weeks
3. Evolution of Nt-ProBNP concentration at randomisation, 12 and 36 weeks.
4. Evolution of collagen biomarkers (PICP and PIIINP) performed at randomisation, at 12 weeks and at 36 weeks
5. Evolution of Biological markers of endothelial dysfunction (endothelin, soluble endothelium selectin (sE-selectin), von Willebrand factor) performed at randomization, at 12 weeks, at 36 weeks
6. Graft function assessed with serum creatinine (micromol/L) with estimation of glomerular filtration rate (eGFR in mL/min/1.73m2) according to the CKD-EPI formula, as well as proteinuria measured by the proteinuria/creatininuria ratio (mg/g). The percentage of patients with GFR ≥ 90, 60-89, 45-59, 30-44, 15-29, <15ml/min/1.73m2 will also be assessed, as well as the percentage of patients with proteinuria/creatininuria ratio <500; 500-1000, 1000-2000, 2000-3000, >3000mg/g at 36Weeks
7. The occurrence of hyperkalaemia between 5 - 5.49; 5.5 - 6; >6mmol/L during 36 weeks follow-up
8. The risk of acute renal failure defined by an increase in creatinine > 50% during follow-up for 36 weeks
9. The echocardiographic characteristics: parameters of systolic function (LVEF, strain), remodeling (ventricular and left atrial volumes), and filling pressures (E/e', deceleration time, PAPs).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

Sponsor organisation

CHRU De Nancy

Address

Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034

City

Nancy Cedex

Postcode

54035

Country

France

Scientific contact point

Organisation

CHRU De Nancy

Contact name

Dr Nesrine BAILI

Public contact point

Organisation

CHRU De Nancy

Contact name

Dr Nesrine BAILI

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 7 files

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

Application history

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