Prevention of Diabetes and Hypertension

Summary

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.

Conditions

• Diabetes Mellitus
• Hypertension

Interventions

BEHAVIORAL

Diet

total fat \< 5%, saturated fat \< 10%, vegetables, fruit

BEHAVIORAL

Moderate exercise

30 min at least 5 times/week

DRUG

enalapril tablets

one Enalapril 10mg tablet once daily for four weeks. Subsequentely one Enalapril 20mg tablet once daily until the end of the randomized treatment phase

DRUG

placebo tablets

one Enalapril placebo tablet and one Losartan placebo tablet once daily until study end.

DRUG

Losartan Tablets

one Losartan 50mg tablet once daily for four weeks. Subsequentely one Losartan 100mg tablet once daily until the end of the randomized treatment phase.

Sponsors & Collaborators

• Italian Society of Hypertension

  collaborator OTHER

• Italian Society of General Practitioners

  collaborator UNKNOWN

• Yghea

  collaborator UNKNOWN

• Istituto Auxologico Italiano

  lead OTHER

Principal Investigators

• Alberto Zanchetti, MD · Istituto Auxologico Italiano. Milan. Italy

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2007-09-30

Primary Completion

2010-03-31

Completion

2010-03-31

Countries

• Italy

Study Locations