E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Kidney graft failure |
Primære formål
At undersøge om man i et randomiseret, placebokontrolleret, dobbeltblindet interventionsforsøg, kan bevare den glomerulære filtrationsrate hos nyretransplanterede patienter, ved tillæg af spironolakton til standardbehandling
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E.1.1.1 | Medical condition in easily understood language |
Failure of transplanted kidneys |
Formålet er at undersøge om tillæg af lægemiddel spironolakton, virker nyrebeskyttende og dermed kan bidrage til længere overlevelse af den transplanterede nyre. |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010185 |
E.1.2 | Term | Complications of transplanted kidney |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 whether renal function in kidney transplant patients can be preserved by the addition of spironolactone to standard treatment |
Ændring i Chrom EDTA clearance (mL/min) |
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E.2.2 | Secondary objectives of the trial |
1. Reduction of renal fibrosis – by morphological and molecular biological studies
2. Reduction of protein excretion in urine
3. Reduction of ambulatory bloodpressure
4. Reduction of number of cardiovascular events
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Ændring i døgnurinprotein (g/døgn)
Ændring i morfologisk renal fibrose undersøgelse af nyrebiopsi, se under patologivariable (vanlig instrukser fra Afdeling for Klinisk Patologi følges, beskrivelserne indeholder klassifikationer som noteres)
Ændring i renal fibrose vurderet ved molekylær biologiske metoder (specificeret under laboratorievariabler)
Ændring i systolisk og diastolisk blodtryk (mmHg), se appendiks blodtryk.
Ændring i kardiovaskulære events (antal tilfælde af AMI, Apopleksi, samt ændring i Hjerteinsuficiens (NYHA klassifikation)).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age > 18 years
2. Treated with a calcineurin inhibitor
3. Proteinuria < 3 g/day
4. Creatinine clearance ≥ 30 mL/min
5. Plasma potassium < 5.5 mmol/L
6. Negative pregnancy test at inclusion for women of childbearing potential and adequate contraception throughout the trial
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De nyretransplanterede patienter rekrutteres i ambulatorierne eller i forbindelse med nyretransplantation på nefrologisk afdeling Y, OUH
Inklusionskriterier
1. Alder > 18 år
2. Behandles med en calcineurinhæmmer
3. Proteinuri < 3 g/døgn
4. Creatnin clearance ≥ 30 ml/min
5. Kalium < 5.5 mmol/L
6. Negativ graviditetstest for fertile kvinder ved inklusionen, samt sikker antikonception under forsøget, dvs. p-piller, spiral eller depot gestagen. Intet ønske om graviditet.
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E.4 | Principal exclusion criteria |
1. Former intolerance of spironolactone
2. Already treated with spironolactone
3. Resonium or Digoxin treatment
4. Pregnancy or planned pregnancy
5. Clinically relevant organic, systemic or psychological disorder
6. Expectation of non-compliance
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Eksklusionskriterier
1. Tidligere intolerance over for spironolacton
2. Allerede i behandling med spironolacton
3. Kreatinin Clearance < 30 ml/min
4. Kalium ≥ 5.5 mmol/L
5. Resonium behandling
6. Digoxin behandling
7. Gravide eller patienter der har planlagt graviditet i under¬søgelsesperioden
8. Psykisk sygdom som gør, at pt. ikke kan gennemføre protokollen
9. Klinisk relevant organisk eller systemisk sygdom inkl. malign lidelse
10. Forventning om manglende samarbejde eller manglende forståelse af forsøget
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E.5 End points |
E.5.1 | Primary end point(s) |
Chrome-EDTA clearance |
Det primære ”endpoint” er ændringer i chrom EDTA clearance fra studiets begyndelse til afslutning. Primæranalysen af dette ”endpoint” udføres under anvendelse af ”LOCF approach”. Sammenligninger udføres på ændringer chrom EDTA clearance. Der anvendes ANCOVA som tager hensyn til behandlingseffekt, forsøgscenter og udgangsværdier |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
0, 1, 2 and 3 years |
Chrom-EDTA-clearence målinger er planlagt som årlig undersøgelse. Henholdsvis inklussionstidspunkt, efter 1,2 og 3 år. |
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E.5.2 | Secondary end point(s) |
• Changes in 24 hour urinary protein excretion
• Change in morphological renal fibrosis by microscopy of the kidney biopsy
• Changes in renal fibrosis assessed by molecular methods
• Changes in systolic and diastolic blood pressure
• Change in the number of cardiovascular events
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Sekundær effekt ”endpoints” omfatter de variable der er beskrevet under punkt E.2.2. Alle indsamlede data summeres per besøg og per behandling. Disse ”endpoints” vil blive sammenlignet på udgangsværdierne med ANCOVA der tager hensyn til behandlingseffekt, forsøgscenter og udgangsværdier |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
0, 1, 2 and 3 years |
Evulering af sekundære endpoints, foregår løbende igennem observationsperioden på 3 år. Der er indlagt kliniske kontroller hver 3.mdr, blod og urinprøver årlig samt faste protokolbiopsier afhængig af transplantationstidspunkt. Kan ses i protokolens observationsplan. |
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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 | 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) | 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 | 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 | 1 |
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 | 3 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |