The purpose of this study is to see whether subjects with gout who receive febuxostat or allopurinol for up to 9 years have a higher rate of serious heart and blood vessel complications (major cardiovascular events). Examples of major cardiovascular events include heart attacks, strokes, and angina (chest pain due to narrowing of the blood vessels of the heart) that need to be treated urgently with a heart operation. The overall duration of the study is dependent on the number of predefined major cardiovascular events (MACE). The length of study is expected to be approximately 9 years in order to observe the required 624 MACE. The length of study participation for each subject will vary due to the event driven study design.
The purpose of this study is to see if subjects with gout who receive febuxostat or allopurinol, once daily (QD), have a higher rate of serious heart and blood vessel complications.
This is a phase 3B multicenter, randomized, double-blind, active-controlled study designed to evaluate the cardiovascular (CV) safety of febuxostat compared with allopurinol in subjects with gout and significant CV comorbidities. Approximately 7500 subjects, males 50 years of age or older or females 55 years of age or older (at least 2-years post-menopausal), with gout and health problems affecting the heart or blood vessels will take part in this study at approximately 450 study centers in North America.
This study will use competitive enrollment. This means that when a target number of subjects has entered the treatment phase of the study, all further screening of subjects will be closed. The length of the study is based on an ongoing review of study results. The participation will last a maximum of 9 years and will include a maximum 28 visits to the study center. Telephone contact will be made every 2 months for subjects who have discontinued the study drug for any reason, but who are asked to continue in the study to be followed for potential cardiovascular events. This study design is called a "Time to Event Study". All study subjects will continue to be followed until enough information has been gathered to determine the overall safety of the study drug.
Gout is caused by high levels of uric acid in the body, and is associated with a broad range of conditions including heart disease, chronic kidney disease and additional risk factors like obesity and high blood pressure. Hyperuricemia, which is defined as an elevation in serum urate levels, develops into gout when urate crystals form from supersaturated body fluids and settle in joints and other organs.
People with gout may also have a higher incidence of other conditions that may be associated with hyperuricemia, gout or both. This is supported by a growing body of research demonstrating that serum urate levels are an independent predictive factor for cardiovascular disease when the effects of other risk factors have been controlled.
This study will explore the cardiovascular safety of febuxostat to determine whether the use of febuxostat is associated with a moderate increase in the risk of serious adverse cardiovascular outcomes as compared to allopurinol.
Participation will last a maximum of 5 years and will include 15 to 20 visits to the study center.
- Febuxostat Drug
Other Names: Uloric; TMX-67 Intervention Desc: Febuxostat 40 mg or 80 mg (depending on serum uric acid levels), capsules, orally, once daily for up to 60 months. ARM 1: Kind: Experimental Label: Febuxostat 40 mg or 80 mg QD Description: (dependent on serum uric acid levels)
- Allopurinol Drug
Intervention Desc: Allopurinol 200 mg to 600 mg (depending on renal function), capsules, orally, once daily for up to 60 months. ARM 1: Kind: Experimental Label: Allopurinol 200 mg to 600 mg QD Description: (dependent on renal function)
- Allocation: Randomized
- Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Safety Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||First occurrence of any event in the predefined Major Adverse Cardiovascular Events Composite.||At first occurrence (up to 60 Months)||Yes|
|Secondary||First occurrence of any Antiplatelet Trialists' Collaborative Event.||At first occurrence (up to 60 Months)||Yes|
|Secondary||First occurrence of Cardiovascular Death death.||At first occurrence (up to 60 Months)||Yes|
|Secondary||First occurrence of Non-fatal Myocardial Infarction.||At first occurrence (up to 60 Months)||Yes|
|Secondary||First occurrence of Non-fatal stroke.||At first occurrence (up to 60 Months)||Yes|
|Secondary||First occurrence of Unstable Angina with Urgent Coronary Revascularization.||At first occurrence (up to 60 Months)||Yes|