E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal failure and left ventricular hypertrophy |
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E.1.1.1 | Medical condition in easily understood language |
Kidney failure and enlarged heart |
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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 |
This study is split into two phases. Phase 1: is a dose finding study. The objective here is to find the minumum dose of allopurinol that will give an average 41% reduction in blood urate levels
Phase 2 is the Main Trial. The primary objective here will be to see if Allopurinol can reverse harmful thickening of the heart muscle wall in patients undergoing dialysis. |
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E.2.2 | Secondary objectives of the trial |
• To determine if there is a change in the efficiency of the hearts pumping capacity with allopurinol in dialysis patients compared with placebo. •To determine if there is a difference in how healthy the blood vessels are with allopurinol compared with placebo in patients with ESRD •To determine if there are changes in blood tests which indicate inflammation in ESRD with allopurinol compared with placebo. •To assess, if there are changes in Blood pressure control with allopurinol compared with placebo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• are aged 18 to 80 years • end stage renal disease (CKD stage 5 eGFR <15ml/min /1.73m2) • been on haemodialysis for at least 3 months. • For main study also require echocardiographic LVH according to the ASE (American Society of Echocardiography) criteria of LVM ≥115g/m2 for men and >95g/m2 for women. • All concomitant medication will be allowed and continued unchanged unless clinically indicated during the study.
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E.4 | Principal exclusion criteria |
• Known heart failure • Left Ventricular Ejection Fraction <45%, • already had gout or on allopurinol, • severe hepatic disease • or on azathioprine, 6 mercaptopurine, theophylline or warfarin. • malignancy or other life threatening diseases, • pregnant or lactating women • any contraindication to MRI (claustrophobia, metal implants). • with a planned (relative) kidney transplant, • Aged less than 18 or over 80 years • Above ankle amputees • Patients who have participated in any other clinical trial within the previous 30 days will be excluded. • Patients who are unable to give informed consent will also be excluded from this trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome of the pilot study is to determine the minimum dose of allopurinol to induce an average 41% decrease in serum urate levels.
The primary outcome in the main trial is to determine if allopurinol, induces a change in Left ventricular Mass Index in patients with ESRD when compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For the pilot study this can be 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weks or 6 weeks .
For the main trial primary outcome is at 12 months |
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E.5.2 | Secondary end point(s) |
1. To determine if there is a change in LV end systolic volume, LV end diastolic volume or LV ejection factor with allopurinol in ESRD patients compared with placebo. 2. To determine if there is a difference endothelial function with allopurinol compared with placebo, measured by FMD and PWA 3. To determine if there are changes in inflammatory blood markers, in ESRD with allopurinol compared with placebo. 4. To assess, if there are changes in BP control as measured by clinic BP and 24hr BP monitoring with allopurinol compared with placebo
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- 12 months 2- 9 months and 12 months 3- 6 months,9 months, 12 months 4- 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 | No |
E.6.3 | Therapy | No |
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 | Yes |
E.8.1.5 | Parallel group | No |
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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Last visit of last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |