E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease |
Kronisk nyresygdom |
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E.1.1.1 | Medical condition in easily understood language |
Chronic kidney disease |
Kronisk nyresygdom |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to investigate whether dapagliflozin reduces LV mass in patients with chronic kidney disease compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to identify cardiovascular and renal biomarkers by which potential effects of dapagliflozin among patients with CKD can be attributed to. These include cardiac biomarkers, function and hemodynamics, metabolic, and renal parameters. Additional exploratory endpoints include measurement of depressive symptoms, quality of life, and cognitive impairment. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A subgroup of CKD patients undergoing dialysis will be included Title: The cardioprotective effects of dapagliflozin in CKD patients on dialysis Version: 9.1 Primary endpoints: - Change in LVMI assessed by echocardiography at 6 months
Secondary endpoints: - Change in residual kidney function - Change in NT-proBNP - Change in volume status assessed by bioimpedance analysis at 6 months - Change in blood pressure before and after hemodialysis (or 24h blood pressure) at 6 months - Change in ultrafiltration at 6 months - Numbers of intradialytic hypertensive episodes during treatment - Registration of antihypertensive or diuretics - Change in inferior vena cava diameter measured by echocardiography at 6 months - Change in weight at 6 months
- All endpoints stated in the overall population |
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E.3 | Principal inclusion criteria |
- Signed informed consent - ≥ 18 years of age For those not undergoing dialysis - Chronic Kidney Disease (CKD), defined as evidence of decreased eGFR (eGFR >=20 and <60 mL/min/1.73 m2) or evidence of albuminuria present for > 3 months if eGFR >60 at least 3 months before and at the time of screening - Stable treatment with clinically appropriate doses of ACEi/ARB among CKD patients with proteinuria and uptitrated to maximal recommended or tolerated dose for at least 4 weeks before randomization, if not medically contraindicated - For patients with type 2 diabetes: o Stable antihyperglycemic treatment > 30 days before screening - Female patients should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing one of the following methods of contraception throughout the study and for 30 days after study completion: Hormonal contraception (oral contraceptives, contraceptive implant, injectable birth control, contraceptive patch, or vaginal ring) or intrauterine device - Ability to understand and read Danish - For those undergoing hemodialysis: - Initation of hemodialysis within 1 year of the randomization visit
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E.4 | Principal exclusion criteria |
- Type 1 diabetes For patients with type 2 diabetes: - History of diabetic ketoacidosis
- History of organ transplant - Treatment with SGLT2 inhibitor within 8 weeks (not undergoing dialysis) or 4 weeks (undergoing dialysis) prior to enrolment - Known allergy or hypersensitivity to SGLT2 inhibitors or Placebo ingredients - Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks of enrolment - Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment - Any condition outside the renal and cardiovascular study area with a life expectancy of <2 years based on investigator’s clinical judgement For non-dialysis participants - Hepatic impairment (aspartate transaminase or alanine transaminase >3 times the upper limit of normal [ULN] or total bilirubin >2 times the ULN at the time of enrolment) For dialysis participants - Known hepatic impairment documented in the participants electronic health record - Known blood-borne diseases, such as Hepatitis A, B, C, D, and E, and Human immunodeficiency virus (HIV) types 1 and 2, Ebola, Lassa fever virus. - Female patients who are pregnant, lactating, or are considering becoming pregnant during the study or for 6 months after study completion - Participation in another clinical study with an investigational product within the last month prior to enrolment - Inability to understand or comply with the investigational product, procedures, and/or follow-up or any conditions that may prevent the participant to complete the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in LV mass index assessed by echocardiography |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in measurements of cardiac structure and function assessed by echocardiography - Change in measurements of cardiac and inflammatory biomarkers - Change in measurements of renal biomarkers - Change in measurements of metabolic biomarkers - Change in measurements of arterial stiffness assessed by applanation tonometry
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |