E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
heart transplant recipients in follow-up |
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E.1.1.1 | Medical condition in easily understood language |
heart transplant recipients in follow-up |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 main goal of this study is to evaluate the effect of oral dapagliflozin on renal function in cardiac allograft recipients. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess the impact of treatment on: i) weight, ii) proteinuria in the subset of patients with an albumin / creatinine ratio in the urine > 30, and iii) blood levels of glycated haemoglobin (HbA1c) in patients with diabetes mellitus, as well as iv) safety. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be screened for eligibility during routine follow-up more than 1 year after heart transplant. All the following conditions must apply prior to administering the investigational medicinal product: Heart transplant recipient for ≥ 1 year. Age ≥ 18 years. Informed consent obtained and documented according to Good Clinical Practice (GCP), and national/regional regulations. Estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2 as assessed by the MDRD formula. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: Contraindications to study medication. Estimated GFR < 25 ml/min/m2 Type I diabetes Severe liver failure (Child-Pugh’s score C) Life expectancy reduced to < 2 years as judged by the investigator Unresolved malignant disease Failure to obtain written informed consent SGL2 inhibitor treatment over the four weeks prior to randomisation Pregnancy Breast-feeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the slope of the eGFR from 2 weeks to end-of-treatment (12 months), calculated as the difference in eGFR from two weeks to 12 months after start of the intervention. The eGFR is calculated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) formula. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From 2 weeks to end-of-treatment (12 months) |
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E.5.2 | Secondary end point(s) |
Baseline-adjusted body weight The change in the albumin / creatinine ratio in the urine from baseline to end-of-treatment in patients with a baseline ratio > 30 mg/g at baseline The change in the blood level of glycated haemoglobin (HbA1c) in patients with diabetes mellitus
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From 2 weeks to end-of-treatment (12 months) |
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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 | Yes |
E.6.3 | Therapy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Yes |
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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The investigational medicinal products will be administered once daily for one year. No other study-specific intervention will be provided. Beyond the first year, the patients are invited to enter the open-label follow-up phase, where the code for the individual patient is opened, and patients who were originally allocated to dapagliflozin will be encouraged to continue treatment; whereas patients assigned to placebo will continue standard-of-care treatment. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |