Evaluating the short-term renal and systemic effects of Dapagliflozin in non-diabetic patients with stage IV CKD at risk of ESKD because of severe renal insufficiency and persistent proteinuria: A prospective, randomized, double-blind, placebo-controlled, cross-over study
- Conditions
- on-diabetic stage IV Chronic Kidney Disease (CKD)MedDRA version: 21.1Level: LLTClassification code 10009119Term: Chronic renal failureSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Male diseases of the urinary and reproductive systems [C12]
- Registration Number
- EUCTR2021-000726-10-IT
- Lead Sponsor
- IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 32
1Provision of informed consent prior to any study specific procedures
2Male or female more than 18 year old
3Non-diabetic Stage-IV CKD
4Fasting blood glucose = 125 mg (= 6.9 mmol/l) and HbA1C =6.4% (= 47 mmol/mol)58 without treatment with oral blood glucose lowering medications and/or insulin
5Two-hour plasma glucose <200 mg/dl during 75-g oral glucose tolerance test (OGTT)58
6Persistent proteinuria (24-hour urinary protein excretion = 0.5 grams in at least two consecutive evaluations >1 week apart) despite RAS inhibitor therapy with ACE inhibitors and/or ARBs (or without RAS inhibitors in patients with specific contraindications to these medications)
7eGFR 15 to 30 ml/min/1.73 m2 by CKD-Epi equation
8Blood pressure <150/90 mmHg without changes in blood pressure lowering medications over the last four weeks before the randomization
9Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
10Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of dapagliflozin\placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
11Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of IMP to prevent pregnancy in a partner.
12Subjects who are blood donors should not donate blood during the study and for 3 months following their last dose of dapagliflozin\placebo.
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 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16
1Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2Participation in another clinical study with an investigational product during the last month
3Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2-inhibitor associated reduction in sodium pool and kidney perfusion pressure)
4Rapidly progressive kidney disease (e GFR reduction = 30% over the last three months) and expected risk of progression to end stage kidney failure and need of renal replacement therapy by dialysis or transplantation during the study period.
5Active systemic autoimmune diseases;
6Concomitant treatment with steroids or any other immunosuppressive agent
7Hypersensitivity to the active principle (dapagliflozin) or any of the excipients (e.g. lactose);
8Severe/unstable heart failure with or without decreased systolic function requiring hospitalization or changes in pharmacological therapy over the last three months
9Uncontrolled hypertension (BP >150/90 mmHg despite optimized pharmacological treatment and diet or symptomatic hypotension
10Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening
11Known to have tested positive for human immunodeficiency virus
12Drug or alcohol abuse
13Inability to fully understand the possible risks and benefits related to study participation
14If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period;
15 If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
16Participation in another interventional clinical trial within the 4 weeks prior to screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method