ADVANCE: Lessons from the run‐in phase of a large study in type 2 diabetes

BACKGROUND: ADVANCE is a major international trial assessing the effects of routine compared with more intensive blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes, among high-risk individuals with type 2 diabetes. We describe the experience of participants receiving active blood pressure lowering therapy during the run-in phase of the study, and the characteristics of participants who withdrew during this phase. METHODS: All participants potentially eligible for inclusion in ADVANCE underwent 6 weeks of therapy with fixed low-dose perindopril 2 mg and indapamide 0.625 mg combination daily, as part of an active run-in phase of the study. This treatment was provided in addition to the participants' existing therapeutic regimen, including other blood pressure lowering drugs. RESULTS: Of the 12 878 registered participants who entered the run-in phase, 11140 participants were randomized. Only 459 participants (3.6%) withdrew due to suspected intolerance of perindopril-indapamide. The mean blood pressure fell by an average of 8/3 mmHg from 145/81 mmHg (standard deviation 22/11 mmHg) to 137/78 (20/10). Participants who proceeded to randomization were broadly similar to those who withdrew during the run-in phase; however, some features suggest that those randomized were a higher risk group overall. CONCLUSIONS: A substantial fall in blood pressure was observed following 6 weeks of treatment with a fixed low-dose combination of perindopril-indapamide in a broad range of high-risk individuals with type 2 diabetes. Good tolerability and safety of the study drug was confirmed during the active run-in phase of the ADVANCE study.