A rotation study of different albuminuria lowering drug classes to study individual drug response in diabetic and non diabetic CKD
- Conditions
- Chronic Kidney DiseaseMedDRA version: 21.1Level: LLTClassification code 10009119Term: Chronic renal failureSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2017-004641-25-IT
- Lead Sponsor
- IVERSITY MEDICAL CENTER GRONINGE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 46
eGFR > 30 and < 90 ml/min/1.73m2
Albuminuria = 100 mg/24 hour and = 3500 mg/24 hour
Serum potassium = 5.0 mmol/L
Treatment with ACEi or ARB
Age = 18 years
Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26
Diagnosis of type 1 diabetes mellitus
Urinary protein excretion > 3500 mg/24 hour
Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis
Indication for immunosuppressants as per the treating physician’s judgment.
Receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment.
Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
Diabetes type 2 patients with recent (last 6 months) of hyperosmolar hyperglicemic state who are prone to development redistributive hyperkalemia (movement of potassium out of the cells)
Pregnant women and women of child-bearing potential who are not using reliable contraception
Cardiovascular disease: myocardial infarction, angina pectoris, percutanous transluminal coronary angioplasty, coronary artery bypass grafting, stroke, heart failure (NYHA I-IV) < 6 months before inclusion
Uncontrolled blood pressure (office blood pressure > 160 / 100 mmHg)
History of autonomic dysfunction (e.g. history of fainting or clinically significant orthostatic hypotension)
History of amputations
eGFR change > 30% in the last six months before study randomization
Current therapy with renin inhibitor or MRA
Concomitant treatment with ACEi and ARB
Intolerance or contraindications to drugs inhibiting the Renin-Angiotensin-Aldosterone System (RAAS). Cyclosporine A, tacrolimus, trimethoprim due to increased risk of hyperkalemia in combination with eplerenone. Ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazadone, lithium, amiodarone, diltiazem, verapamil due to increase in toxicity when combined with eplerenone. Rifampicin, carbamazepine, phenytoin, phenobarbital due the risk of decreased eplerenone efficacy.
Participation in any clinical investigation within 3 months prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing
History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the correlation between individual albuminuria lowering responses of the MRA eplerenone, SGLT2 inhibitor dapagliflozin and their combination in patients with chronic kidney disease ;Secondary Objective: To determine the correlation between office/home blood pressure-lowering responses of eplerenone, dapaglifozin and their combination.<br>To determine which patients characteristics predict the albuminuria and blood pressure response to eplerenone, dapagliflozin and their combination;Primary end point(s): Correlation between individual albuminuria response between eplerenone and dapagliflozin.;Timepoint(s) of evaluation of this end point: 24 weeks which corresponds to the sum of the three treatment periods plus the three wash-out periods
- Secondary Outcome Measures
Name Time Method Secondary end point(s): the degree of correlation in either office or home blood pressure-lowering responses with eplerenone and dapagliflozin<br>; Correlation between selected biomarkers of interest at baseline such as NT-proBNP and change in albuminuria from baseline during interventions;Timepoint(s) of evaluation of this end point: 24 weeks which corresponds to the sum of the three treatment periods plus the three wash-out periods; 24 weeks which corresponds to the sum of the three treatment periods plus the three wash-out periods