E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease with albuminuria |
Kronisk nyresygdom med albuminuri |
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E.1.1.1 | Medical condition in easily understood language |
Chronic kidney disease with protein in the urine |
Kronisk nyresygdom med æggehvidestof i urinen |
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E.1.1.2 | Therapeutic area | Not possible to specify |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020647 |
E.1.2 | Term | Hyperkalemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001580 |
E.1.2 | Term | Albuminuria |
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 |
To investigate if concomitant treatment with Patiromer will lead to a greater reduction in albuminuria when compared to treatment without Patiromer in patients with chronic kidney disease, albuminuria and a history of hyperkalemia. This is based on the notion, that concomitant treatment with the potassium binder Patiromer will allow for more intensive treatment with inhibitors of the renin-angiotensin-aldosterone system (Losartan and/or Spironolactone) leading to reduction in albuminuria being an established surrogate marker of the progression of chronic kidney disease.
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At undersøge om samtidig behandling med Patiromer fører til en større reduktion i graden af albuminuri sammenlignet med behandling uden Patiromer hos patienter med kronisk nyresvigt, albuminuri og tendens til hyperkaliæmi.
Dette er baseret på antagelsen om, at samtidig behandling med kaliumbinderen Patiromer vil tillade mere intensiv behandling med hæmmere af renin-angiotensin-aldosteron-systemet (Losartan og/eller Spironolacton) førende til en reduktion i graden af albuminuri, som er en surrogat-markør for progression af kronisk nyresygdom. |
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E.2.2 | Secondary objectives of the trial |
The study will further investigate, if concomitant treatment with Patiromer and a more intensive treatment with inhibitors of the renin-angiotensin-aldosterone system (Losartan and/or Spironolactone) in patients with chronic kidney disease, albuminuria and a history of hyperkalemia will lead to changes in blood pressure control, kidney function, plasma-potassium, intake of potentially healthy, potasium rich foods such as fruit and vegetables, quality of life as well as a number of markers of cardiovascular health including left ventricular ejection fraction, pulse wave velocity, and cardiovascular biomarkers, when compared to patients not treated with Patiromer. Furthermore, the study will assess the safety of concomitant treatment with Patiromer and a more intensive treatment with inhibitors of the renin-angiotensin-aldosterone system (losartan and/or spironolactone) by comparing the incidence of severe hyperkalemia and acute renal failure. |
Studiet vil videre undersøge, om samtidig behandling med Patiromer og mere intensiv behandling med hæmmere af renin-angiotensin-aldosteron-systemet (Losartan og/eller Spironolacton) hos patienter med kronisk nyresvigt, albuminuri og tendens til hyperkaliæmi vil føre til ændringer i blodtrykskontrol, nyrefunktion, plasma-kalium, indtag af sunde, kaliumholdige fødevarer som frugt og grønt, livskvalitet og en række markører for kardiovaskulær sygdom, inklusiv venstre-ventrikel-ejection-fraction, pulsbølgehastighed og kardiovaskulære biomarkører, sammenlignet med patienter der ikke behandles med Patiromer. Envidere vil studiet undersøge sikkerheden af samtidig behandling med Patiromer og samtidig mere intensiv behandling med hæmmere af renin-angiotensin-aldosteron-systemet (Losartan og/eller Spironolacton) with at sammenligne incidensen af svær hyperkaliæmi og akut nyresvigt. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18-80 years 2. eGFR 25-60 mL/min/1.73 m2 3. Latest P-potassium > 4.5 mmol/L or b) P-kalium > 4.5 mmol/L at least twice within the last 24 months 4. Urine albumin creatinine ratio > 500 mg/g or 200mg/g and diabetes
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1. Alder 18-80 år 2. eGFR mellem 25-60 mL/min/1.73 m2 3. a) Seneste P-kalium > 4.5 mmol/L eller b) P-kalium > 4.5 mmol/L mindst 2 gange i løbet af de seneste 24 måneder 4. Urin albumin/kreatinin-ratio > 500 mg/g eller 200mg/g og diabetes
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E.4 | Principal exclusion criteria |
1. Intolerance or allergic to Losartan, Spironolactone or Patiromer 2. Previous renal transplant recipient or active on the waiting ling 3. End stage renal disease (defined as the need for dialysis or renal transplantation) 4. Any condition that currently or through the duration of the study would require specific immunosuppressive therapy 5. Pregnancy 6. Regular use of Trimethoprim and/or NSAIDs 7. Disseminated cancer disease 8. Addisons disease 9. History of heart failure defined as Ejection Fraction (EF) < 40% or currently receiving treatment at a heart failure clinic or similar 10. Porphyria 11. Severe constipation requiring daily and chronic use of laxatives and/or previous recurrent ileus (> 1 incident in the past 10 years without curative treatment 12. Fructose intolerance 13. Galactose intolerance 14. A history of severe liver insufficiency (Child–Pugh score B-C) 15. SGLT2-inhibitor treatment initated ≤ 30 days prior to inclusion
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1. Intolerance eller allergi over for både ACE-I og Losartan eller Spironolacton eller patiromer 2. Tidligere nyretransplantation eller aktiv på venteliste til nyretransplantation 3. ESRD (defineret som behov for dialyse eller nyretransplantation) 4. Enhver lidelse der aktuelt eller forventeligt i løbet af studiet vil kræve specifik immundæmpende behandling 5. Graviditet eller manglende mulighed for at bruge sikker antikonception, dvs. spiral eller hormonel (p-piller, implantat, transdermal depotplaster, vaginalring eller depotinjektion) 6. Regelmæssigt behov for brug af trimethoprim og/eller NSAID-præparater 7. Dissemineret cancer-sygdom 8. Addisons Sygdom 9. Hjertesvigt defineret som kendt Ejection Fraction (EF) < 40% eller pågående behandlingsforløb i hjertesvigtsklinik eller tilsvarende. 10. Porfyri. 11. Svær opstipation med behov for kronisk og fast laksantiabehandling og/eller tidligere og recidiverende ileus-tilstand (> 1 tilfælde de seneste 10 år , som ikke er kurativt behandlet) 12. Fruktoseintolerans 13. Galactoseintolerans 14. Svær leverinsufficiens (Child–Pugh score B-C) 15. Behandling med SGLT2-hæmmer opstartet ≤ 30 dage forud for inklusion
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E.5 End points |
E.5.1 | Primary end point(s) |
The difference in the change in albuminuria (urinary albumin/creatinine ratio) between patients assigned to treatment with Patiromer and patients not assigned to Patiromer as evaluated by the average of 2 morning spot urine samples. |
Forskellen mellem ændringen i graden af albuminuri (Urin-albumin/kreatinin ratio) vurderet ud fra gennemsnittet af 2 morgen spot-urin målinger hos patienter randomiseret til behandling med Patiromer sammenlignet med patienter radomiseret til behandling uden Patiromer. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization to end of study (52 weeks)
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Fra randomisering til studiets afslutning (52 uger)
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E.5.2 | Secondary end point(s) |
1. The difference in amount of albuminuria between the two groups evaluated by a spot urine sample and a 24h urine collection at the end of treatment. 2. The difference in the change of albuminuria between the two groups evaluated by a 24h urine collection from randomization to the end of trial 3. The difference in the extent of treatment with inhibitors of the renin-angiotensin-aldosterone-system (Losartan and/or Spironolactone) between the two groups at the end of trial. 4. The difference in the change of the extent of treatment with inhibitors of the renin-angiotensin-aldosterone-system (Losartan and/or Spironolactone) between the two groups from randomization to the end of trial. 5. The difference in renal function (eGFR and urine-creatinine-clearance) between the two groups and the end of treatment. 6. The difference in the change in renal function (eGFR and urine-creatinine-clearance) between the two groups from randomization to the end of treatment. 7. The difference in blood pressure (ambulatory and 24h) between the two groups at the end of treatment. 8. The difference in the change in blood pressure (ambulatory and 24h) between the two groups from randomization to the end of treatment. 9. The difference in pulse-wave-velocity between the two groups at the end of treatment. 10. The difference in the change in pulse-wave-velocity between the two groups from randomization to the end of treatment. 11. The difference in left-ventricular function (ejection fraction) between the two groups at the end of treatment. 12. The difference in the change in left-ventricular function (ejection fraction) between the two groups from randomization to the end of treatment. 13. The difference in cardiac biomarkers between the two groups at the end of treatment. 14. The difference in the change in cardiac biomarkers between the two groups from randomization to the end of treatment. 15. The difference in P-potassium between the two groups at the end of treatment. 16. The difference in the number of episodes with severe hyperkalemia (P-potassium > 6.2mmol/L) between the two groups from randomization to the end of treatment. 17. The difference in the number of episodes with acute renal failure between the two groups from randomization to the end of treatment. 18. The difference in the amount of fruit and vegetables in the diet between the two groups at the end of treatment. 19. The difference in the change in amount of fruit and vegetables in the diet between the two groups from randomization to the end of treatment. 20. The difference in the change the quality of life between the two groups from randomization to the end of treatment. |
1. Forskel i graden af albuminuri mellem de to interventionsgrupper vurderet ud fra hhv. spoturinmåling (jfr. ovenfor) og en døgnurin-opsamling ved behandlingens afslutning. 2. Forskel i ændringen i albuminuri mellem de to interventionsgrupper vurderet ud fra en døgnurin-opsamling fra randomisering til behandlingens afslutning. 3. Forskel i omfanget af behandling med hæmmere af renin-angiotensin-aldosteron-systemet (losartan og/eller spironolakton) mellem de to interventionsgrupper ved behandlingens afslutning. 4. Forskel i ændringen i omfanget af behandling med hæmmere af renin-angiotensin-aldosteron-systemet(Losartan og/eller Spironolakton) mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 5. Forskel i nyrefunktion (eGFR hhv. urin-kreatinin clearance) mellem de to interventionsgrupper ved behandlingens afslutning. 6. Forskel i ændringen i nyrefunktion (eGFR hhv. urin-kreatinin clearance) mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 7. Forskel i blodtryk (konsulationsblodtryk hhv. døgnblodtryk) mellem de to interventionsgrupper ved behandlingens afslutning. 8. Forskel i ændringen i blodtryk (konsulationsblodtryk hhv. døgnblodtryk) mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 9. Forskel i pulsbølgehastighed mellem de to interventionsgrupper ved behandlingens afslutning. 10. Forskel i ændringen i pulsbølgehastighed mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 11. Forskel i venstre ventrikelfunktion (ejection fraction) mellem de to interventionsgrupper ved behandlingens afslutning. 12. Forskel i ændringen venstre ventrikelfunktion (ejection fraction) mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 13. Forskel i kardielle biomarkører mellem de to interventionsgrupper ved behandlingens afslutning. 14. Forskel i ændringen kardielle biomarkører mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 15. Forskel i P-kalium mellem de to interventionsgrupper ved behandlingens afslutning. 16. Forskel i antallet af episoder med svær hyperkaliæmi (P-kalium >6.2 mmol/L) mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 17. Forskel i antallet af episoder med akut nyresvigt mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 18. Forskel i indtagelsen af frugt og grønt mellem de to interventionsgrupper ved behandlingens afslutning. 19. Forskel i ændringen indtagelsen af frugt og grønt antallet mellem de to interventionsgrupper fra randomisering til behandlingens afslutning. 20. Forskel i ændringen i livskvalitet mellem de to interventionsgrupper fra randromisering til behandlingens afslutning. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
: At the end of treatment (52 weeks after randomization) 2, 4, 6, 8, 10, 12, 14, 16, 17, 19, 20: From randomization to the end of treatment (52 weeks) |
1, 3, 5, 7, 9, 11, 13, 15, 18: Ved studiets afslutning (52 uger efter randomisering) 2, 4, 6, 8, 10, 12, 14, 16, 17, 19, 20: Fra randomisering til studiets afslutning (52 uger)
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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 | 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 | Yes |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard klinisk praksis (uden Patiromer) |
Standard clinical care (without Patiromer) |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |