Background. Antihypertensive therapy with ß-blockers (ßBs) and diureticts (Ds) is accompanied
by a higher incidence of diabetes mellitus (DM) than therapy with ACE-inhibitors (ACEIs) or
angiotensin-receptor blockers (ARBs). Whether this difference is due to an antidiabetogenic
action of ACEIs and ARBs or to the fact that these agents are free of the diabetogenic
activity of ßBs and Ds is unknown. Prevention of DM as well as of HT is of primary health
concern.
Objectives. The primary objective of PHIDIAS is to test whether in individuals with
components of metabolic syndrome making them predisposed to DM and HT, addition of either an
ACEI or an ARB to periodically reinforced lifestyle counselling can reduce 1) onset of DM and
2) onset of HT significantly more than lifestyle plus placebo. Secondary objectives are 1)
comparing the antidiabetogenic effects of ACEI and ARB, and 2) investigating whether the
effects of ACEI and ARB on DM and HT persist at least 6 months after treatment withdrawal.
Methods. PHIDIAS is a prospective, double-blind, placebo-controlled 3-arm comparison trial.
300 general practitioners (members of SIMG with the assistance of hospital centres of SIIA)
will randomise 6000 untreated individuals aged 40-75 years, with SBP 130-139 or DBP 85-89
mmHg, fasting glucose (FG) 100-125 mg/dl, waist circumference >= 102 (M) or >= 88 cm (W), to
three blinded treatments, given in addition to lifestyle advise: 1) Placebo; 2) the ACE
Enalapril (10 mg, then 20 mg od); 3) the ARB Losartan (50 mg, then 100 mg od).Double-blind
treatment will be maintained until 500 cases of DM are observed (presumably average of 36
months) (Treatment Phase: control visits, BP, FG every 6 months). This will be followed by a
6-month Withdrawal Phase (active treatment substituted by placebo). Primary outcomes are DM
(FG >= 126 mg/dl) and HT (SBP >= 140 or DBP >= 90 mmHg) on 2 consecutive visits. PHIDIAS will
be governed by a Steering Committee assisted by a blinded Event Adjudicating Committee and an
independent DMSB.
Expected results. The sample size is adequate (alfa 5%, power 90%) to evaluate whether
incident DM (expected rate 3.5%/year) or incident HT is reduced 25% by ACEI and ARB versus
placebo (primary hypothesis) and whether either the ACEI or the ARB reduces incident DM by
30% more than the other agent.
Phase:
Phase 4
Details
Lead Sponsor:
Istituto Auxologico Italiano
Collaborators:
Italian Society of General Practitioners Italian Society of Hypertension Yghea