ADVANCE: lessons from the run-in phase of a large study in type 2 diabetes

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.

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.

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.

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.