Action in Diabetes and Vascular Disease Preterax and Diamicron-MR Controlled Evaluation (ADVANCE-ON)
The blood pressure lowering comparison of the ADVANCE trial has demonstrated a clear reduction in mortality and total vascular events, with a trend towards separately important reductions in major macrovascular events and major microvascular events.
The blood glucose lowering comparison of the ADVANCE trial aiming for an HbA1c of less than 6.5% demonstrated a clear reduction in microvascular and renal events and a trend towards reduction in all-cause mortality, cardiovascular death and macrovascular events during the last 12 - 18 months of follow-up.
Against this background the UKPDS (a smaller study of a patient group with on average less severe and more recently diagnosed diabetes) has recently reported post-trial benefits of a former period of intensive glucose control on death and macrovascular events. These post-trial benefits were achieved despite an early loss of between group differences in glycaemic control. As such, these long term benefits have been ascribed to a "metabolic memory" or "legacy" effect.
Whether the same benefits would be observed in patients with longer periods of hyperglycaemia and established vascular disease as studied in the ADVANCE trial remains unknown.
Aims
To examine the long term effects of the ADVANCE interventions (routine blood pressure lowering with perindopril-indapamide versus placebo and intensive glucose lowering with a gliclazide MR-based regimen versus standard glucose control) on the two primary clinical outcomes of death from any cause and major macrovascular events after the completion of randomised intervention.
Hypothesis: During post-trial follow-up and following completion of randomized intervention, there will be persistent or emerging health benefits in the ADVANCE participants that were initially assigned to the active intervention groups (perindopril-indapamide and intensive glucose control) as compared to those assigned to the control groups (placebo and standard glucose control).
Methods
- Post-trial observational study
- All ADVANCE sites
- All living ADVANCE participants
Phase One: Up to five years follow-up post-T2 (funded)
Phase Two: Up to 10 years follow-up post-T2 (subject to funding)
This study comprises the long-term post-trial follow-up of all surviving ADVANCE trial participants. During the ADVANCE trial, participants were assigned in a factorial design to:
- Routine additional blood pressure lowering compared to placebo and
- Intensive glucose control with a gliclazide MR-based regimen compared to standard glucose control.
The randomised interventions were discontinued at the completion of trial follow-up in 2008. Participants have since been returned to the care of their usual practitioners. It is anticipated that the patterns of blood pressure management and glucose control in the randomised groups will have converged since the completion of the trial and the cessation of the randomised interventions. The goal of this project is to determine whether there is a convergence of the levels of risk for clinical outcomes that matches the convergence of these exposure levels in the five to ten years following completion of the trial.
ADVANCE-ON is part funded by an unrestricted educational grant from Servier. Additional funding is being sought from research agencies, pharmaceutical companies and other industry sponsors around the world. Further funding will enable collection of additional data and extension of follow-up by a further five years.
Timeline
- Recruitment commenced: Q1 2010
- Recruitment completed: Q4 2010
- Phase one follow-up completed: Q4 2013
- Phase one results published: Q2 2014
- Phase two follow-up completed: Q4 2018
- Phase two results published: Q2 2019
Funding
ADVANCE-ON is part funded by an unrestricted educational grant from Servier. Additional funding is being sought from research agencies, pharmaceutical companies and other industry sponsors around the world. Further funding will enable collection of additional data and extension of follow-up by a further five years.
Study organisation
