E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Left ventricular hypertrophy in hypertension |
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E.1.1.1 | Medical condition in easily understood language |
Enlarged heart associated with previous high blood pressure |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049773 |
E.1.2 | Term | Left ventricular hypertrophy |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015488 |
E.1.2 | Term | Essential hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular 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 |
The primary research objective is to test if allopurinol can reduce thickening of the heart muscle in patients with treated high blood pressure. |
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E.2.2 | Secondary objectives of the trial |
The secondary research objectives are to find out if allopurinol improves stiffness of arteries in patients with treated high blood pressure. We also aim to find out if adding allopurinol to the participants current high blood pressure treatment improves blood pressure control. Additionally the participants blood tests will be checked to see if there are any changes in markers of inflammation whilst on allopurinol. The MRI scans will be compared against ECG measurements (ECGs can be tolerated by all patients whilst MRIs may not, so if the MRI scan findings are duplicated on the ECG it will help with future assessments of the effect of allopurinol in patients with treated high BP). Finally the MRI scans will also be checked to see if there are any other improvements in the health of the heart, in addition to the primary objective of seeing if it may improve the effect of thickening of the heart. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• are aged over 18 years • previously diagnosed with essential hypertension • been on stable antihypertensive therapy for at least 3 months prior to study screening •have screening ABPM (or home based BP monitoring if ABPM not tolerated) with daytime average systolic <135mmHg •have screening echocardiography based diagnosis of LVH based on ASE criteria (males >115g/m2, females >95g/m2)
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E.4 | Principal exclusion criteria |
• documented intolerance to allopurinol • left Ventricular Ejection Fraction <45% on echocardiography screening • severe aortic stenosis on echocardiography screening • already had gout or currently on allopurinol • severe hepatic disease • renal disease; CKD class 3B or worse • on azathioprine, 6 mercaptopurine, or theophylline • malignancy (receiving active treatment) or other life threatening diseases • pregnant or lactating women • any contraindication to MRI (claustrophobia, metal implants) • patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days will be excluded. • patients who are unable to give informed consent • any other considered by a study physician to be inappropriate for inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is to determine if allopurinol induces a change in Left Ventricular Mass Index in patients with treated hypertension when compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year for primary endpoint |
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E.5.2 | Secondary end point(s) |
1: change in LV Mass, LV end systolic volume, LV end diastolic volume or LV ejection factor 2; difference in endothelial function measured by Flow mediated dilatation and Pulse Wave Analysis. 3: changes in inflammatory and other blood markers 4: changes in BP control as measured by 24hr BP monitoring |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1; 1 year 2; 9 month and 1 year 3; 1 year 4; 1 year |
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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 | 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 | 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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |