E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic symptomatic hyperuricaemic |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10018627 |
E.1.2 | Term | Gout |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition 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 objective of the study is to compare the cardiovascular safety profile of febuxostat versus allopurinol when taken for an average of 3 years in patients over 60 years with chronic hyperuricaemia in conditions where urate deposition has already occurred |
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E.2.2 | Secondary objectives of the trial |
The secondary study objectives are to evaluate other cardiovascular adverse events for both products. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Febuxostat and Allopurinol blood pressure study (Fall-BP), protocol version 1.0, 12-09-13
Sub-study involving 300 randomised FAST patients to determine the effect of febuxostat in comparison with allopurinol on blood pressure as measured by home blood pressure monitoring.
2. The Differential Effect of Febuxostat vs Allopurinol on Left Ventricular Hypertrophy (LVH Substudy), version 1.0 (04-06-14).
Sub-study will use cardiac MRI scans to establish the prevalence of LVH in gout patients and to determine whether treatment with febuxostat will lead to regression of LVH compared to treatment with allopurinol. It will recruit 300 FAST patients in Scotland
3. The Quality of Life (QoL) in Patients with Gout FAST Substudy, Protocol version 1.0 (04-06-14)
Sub-study is a longitudinal QOL assessment of a large number of patients with gout who are receiving optimal treatment with both febuxostat and allopurinol. The QOL sub-study will involve FAST patients completing two short questionnaires (the Gout Assessment Questionnaire and the SF-36 general quality of life questionnaire) around the time of the screening visit for FAST and repeated at their 12 and 24 month annual follow ups. It will involve 800 FAST patients |
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E.3 | Principal inclusion criteria |
1. Male or female patients aged 60 years or over with a least one additional risk factor. *Risk Factors Age ≥70 years (male) or ≥75 years (female) Smoking (current or within the last 2 years) Diabetes mellitus Impaired glucose tolerance Hypertension (SBP > 140mmHg and/or DBP > 90mmHg) or on antihypertensive therapy Dyslipidaemia (investigator opinion) CKD Stage 1-3 Microalbuminuria or proteinuria Family history of coronary heart disease or stroke in first degree relative at age <55 years Inflammatory arthritis (investigator opinion – including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) Chronic NSAID therapy (investigator opinion) Peripheral vascular disease Previous CV event (MI CVA or transient ischaemic attack) Peripheral vascular disease (Investigator / clinical opinion) Chronic obstructive pulmonary disease (COPD) 2. Patients who, in the opinion of the recruiting physician, require treatment for chronic hyperuricaemia where urate deposition has already occurred. 3. Patients who have received ≥90 days treatment with allopurinol, or ≥3 allopurinol prescriptions, within the previous 6 months. 4. Patients, who in the opinion of the study recruiting physician or site coordinator, are eligible for treatment with either allopurinol or febuxostat. 5. Patients who are willing to give permission for their paper and electronic medical records, hospitalisation data, prescribing data, and (in the event of their death) their death certification data to be accessed and abstracted by trial investigators. 6. Patients who are willing to be contacted and interviewed by trial investigators or delegates (suitably trained research nurses), should the need arise (e.g., for adverse event assessment and to determine whether an episode of acute gout has occurred). |
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E.4 | Principal exclusion criteria |
1. Patients who have any contraindication to febuxostat or allopurinol (with reference to the summary of product characteristics). 2. Patients with severe renal impairment (eGFR <30 ml/min as defined by the Cockroft-Gault formula according to creatinine, age, sex and body weight. 3. Patients with moderate or severe hepatic impairment i.e. cirrhosis with clinical and/or biological decompensation (i.e. ascitis, lower limb oedema, icterus or increased prothrombin time >2X reference value) 4. Patients with a life-threatening co-morbidity or with a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol. 5. Patients with malignancy, including haematological malignancy. 6. Patients who have experienced either a myocardial infarction or stroke. 7. Patients whose behaviour or lifestyle would render them less likely to comply with study medication (i.e., abuse of alcohol, substance misuse, debilitating psychiatric conditions or inability to provide informed consent). 8. Patients with an acute gout flare or who are within 14 days of the resolution of a gout flare. 9. Patients currently participating in another clinical trial or who have participated in a trial in the previous 3 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis will be time to event and the endpoint will be the first occurrence of hospitalisation or death due to one or more APTC (Anti-Platelet Trialists’ Collaboration) primary events: • non-fatal myocardial infarction • non-fatal stroke • cardiovascular death |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from randomisation to first occurence of any event |
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E.5.2 | Secondary end point(s) |
:• Hospitalisation for non-fatal MI • Hospitalisation for non-fatal stroke • Cardiovascular death • All cause mortality • Hospitalisation for heart failure • Hospitalisation for unstable, new or worsening angina • Hospitalisation for coronary revascularisation • Hospitalisation for cerebral revascularisation • Hospitalisation for transient ischeamic attack (TIA) • Hospitalisation for non-fatal cardiac arrest • Hospitalisation for venous and peripheral arterial vascular thrombotic event • Hospitalisation for arrhythmia with no evidence of ischaemia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints (in rank order of importance) will be evaluated using a time to event analysis The following endpoints will be evaluated as an incidence rate: • Cardiovascular mortality • APTC events in each treatment arm |
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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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | 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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The end of the trial will be determined by the steering committee and this will occur when more than the required number of primary endpoints has accrued |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 1 |