Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents.Intervention Trial
Status:
Unknown status
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
Summary
Background: In patients with type 2 diabetes inadequately controlled with metformin, two main
therapeutic options are equally plausible: add-on a sulfonylurea (SU) or a thiazolidinedione
(TZD). Since the two classes of drugs clearly differ in terms of mechanisms of action, side
effects, economic costs and cardiovascular risk factors profile, a direct comparison of the
two therapeutic strategies would be most appropriate.
Aims: 1) To evaluate the effects of add-on pioglitazone as compared with add-on a SU on the
incidence of cardiovascular events in type 2 diabetic patients inadequately controlled with
metformin; 2) To compare the two treatments in terms of glycemic control, safety, and
economic costs.
Methods: multicentre, randomised, open label, parallel group trial of 48 months duration.
Eligible participants (type 2 diabetic males and females, aged 50-75 years, BMI 20-45 Kg/m2,
in treatment for the last two months with metformin 2 gr/die in monotherapy and with HbA1c >
=7.0% and <= 9.0%) will be randomized to add-on: a SU - glibenclamide (5-15 mg/die),
gliclazide (30-120 mg/die), glimepiride (2-6 mg/die), chosen according to local practice - or
pioglitazone (15-45 mg/die). A HbA1c value > 8.0 % on two consecutive occasions will lead to
addition of insulin to ongoing oral therapy.
Primary efficacy outcome: a composite endpoint of all-cause mortality, non fatal MI
(including silent MI), non fatal stroke, and unplanned coronary revascularization.
Secondary outcomes. Principal secondary outcome: a composite ischemic endpoint of sudden
death, fatal and non fatal acute MI (including silent MI), fatal and non fatal stroke, major
amputations (above ankle), endovascular or surgical intervention on the coronary, leg or
carotid arteries.
Other secondary outcomes
- a composite cardiovascular end point including the primary end point plus hospitalization
for heart failure, endovascular or surgical intervention on the coronary, leg or carotid
arteries, silent MI, angina - by WHO criteria and confirmed by a new electrocardiogram
abnormality - intermittent claudication with an ankle/brachial index lower than 090; events
of heart failure; a microvascular endpoint including: plasma creatinine increase of 2 times
above the baseline value or creatinine clearance reduction of 20ml/min/1. 73m2 or development
of overt nephropathy (dialysis or plasma creatinine >3,3 mg/dl) or macroalbuminuria; glycemic
control (changes from baseline in HBA1c, time to failure of glycemic control, i.e., HBA1c
>8.0% on two consecutive occasions three months apart); major CV risk factors (lipids, blood
pressure, microalbuminuria, inflammation markers, waist circumference); safety and side
effects; direct and indirect costs.
Data regarding CV endpoints, safety, tolerability, and study conduct will be monitored and
analyzed by an independent committee, and will be not available to the study investigators
until the closing of data collection. Efficacy end points will be analyzed on an
intention-to-treat basis.
Phase:
Phase 4
Details
Lead Sponsor:
Italian Society of Diabetology
Collaborators:
Associazione Medici Diabetologi (AMD) Associazione Nazionale Medici Cardiologi Ospedalieri