E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease with concurrent hypertension and diabetes. |
Chronische nierinsufficientie bij hypertensie en diabetes mellitus. |
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E.1.1.1 | Medical condition in easily understood language |
Chonic kidney disease with concurrent high blood pressure and diabetes. |
Chronische nierschade bij hoge bloeddruk en suikerziekte. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
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 |
To compare the antiproteinuric effect of sacubitril/valsartan and valsartan in patients with stage 3 or stage 4 CKD, with concurrent hypertension and diabetes. |
Het vergelijken van het antiproteinurische effect van sacubitril/valsartan en valsartan in patiënten met chronische nierinsufficientie, hypertensie en diabetes mellitus. |
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E.2.2 | Secondary objectives of the trial |
To compare the effects on ambulatory blood pressure, eGFR, number of AEs and SAEs, parameters of kidney damage, renin-angiotensin-aldosterone system and natriuretic peptide system. |
Het vergelijken van het effect op ambulante bloeddruk, eGFR, aantal AEs en SAEs, parameters van nierschade, renine-angiotensine-aldosteron systeem en natriuretisch peptide systeem. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age > 18 years • Chronic kidney disease stage 3 or 4 (eGFR 15-60 ml/min/1.73m2) • Residual proteinuria during RAAS blockade (≥ 1 g/day) • Diabetes mellitus type 2 • Hypertension (office systolic blood pressure > 140 mmHg OR use of any anti-hypertensive drug) |
Leeftijd > 18 jaar • Chronische nierinsufficientie stadium 3 of 4 (eGFR 15-60 ml/min/1.73m2) • Resterende proteinuria onder RAAS blokkade (≥ 1 g/day) • Diabetes mellitus type 2 • Hypertensie (spreekkamer systolische bloed druk > 140 mmHg OF use of gebruik van antihypertensieve medicatie)
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E.4 | Principal exclusion criteria |
• SBP >180 mmHg at screening • Not possible to withdraw ACEi or ARB • Known intolerance or contraindication for ARB • History of angioedema • Nephrotic syndrome • Rapidly declining kidney function with high likelihood of dialysis or transplantation in the coming 4 months • Use of immunosuppressive drugs • Kidney transplant recipients • Pregnant or breastfeeding women • Life expectancy < 6 months • Inability to adhere to study protocol (due to language, incapacitated subjects, subjects with intellectual disability)
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• Systolische bloeddruk >180 mmHg bij screening • Niet mogelijk om ACEi of ARB te stoppen • Bekende intolerantie of contraindicatie voor ARB • Voorgeschiedenis van angio-oedeem • Nephrotisch syndroom • Snel le achteruitgang nierfunctie waarvoor waarschijnlijk niertransplantatie nodig in de komende 4 maanden • Gebruik van immunosuppressiva • Niertransplantaat ontvangers • Vrouwen die zwanger zijn of borstvoeding geven • Levensverwachting < 6 maanden • Onvermogen om het studieprotocol na te leven (door taalgebreken, verminderd bewustzijn, intellectuele achterstand)
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the reduction in 24-hour proteinuria of sacubitril/valsartan or valsartan in patients with stage 3 or stage 4 CKD, with concurrent hypertension and diabetes. |
Het vergelijken van antiproteinurische effect van sacubitril/valsartan en valsartan in patiënten met chronische nierinsufficientie, hypertensie en diabetes mellitus. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
Niet van toepassing |
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E.5.2 | Secondary end point(s) |
Effects on ambulatory blood pressure, eGFR, number of AEs and SAEs, parameters of kidney damage, renin-angiotensin-aldosterone system and natriuretic peptide system. |
Het vergelijken van het effect op ambulante bloeddruk, eGFR, aantal AEs en SAEs, parameters van nierschade, renine-angiotensine-aldosteron systeem en natriuretisch peptide systeem. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
Niet van toepassing |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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LVLS |
Laatste bezoek van laatste deelnemer. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |