Prevention of Diabetes and Hypertension

• Status: Terminated
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Istituto Auxologico Italiano
• Collaborators: Italian Society of General Practitioners; Italian Society of Hypertension; Yghea
• Treatments: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Enalaprilat; Losartan

Criteria

Inclusion Criteria:

• Men or women of any racial background

• Age >= 40 years and <= 75 years

• SBP>= 130 mmHg and < 140 mmHg or DBP >= 85 mmHg and < 90 mmHg, average of screening and randomisation visits (in absence of any antihypertensive medication)

• FG >=100 mg/dl (5.6 mmol/l) and < 126 mg/dl (7.0 mmol/l) between screening and randomisation (in absence of any antidiabetic medication)

• Waist circumference >= 102 cm in men and >= 88 cm in women.

Exclusion Criteria:

• SBP >= 140 mmHg or DBP >= 90 mmHg

• Any antihypertensive, antidiabetic or antiobesity medication at the time of or during the 6 months previous to randomisation

• Any current or previous cardiovascular or renal disease requiring continuous administration of Ds, ßBs, ACEIs, ARBs, CAs, and any other antihypertensive medication

• Any medical condition preventing adherence to lifestyle measures included in the protocol

• Hepatic disease as AST (SGOT) or ALT (SGPT) values equal or greater than two times the upper limit of normal

• Chronic renal dysfunction as serum creatinine > 2.0 mg/dl

• Any gastrointestinal disorder interfering with drug absorption

• Known allergy or contraindications to ACEIs or ARBs

• Pregnant or lactating women; women in reproductive age not using recognized contraceptive methods

• Malignancy within the last 5 years

• Clinically significant autoimmune disorders

• Drug abuse or alcohol abuse within the last 5 years

• History of noncompliance to medical regimens

• Incapacity or unwillingness to sign the informed consent

• Participation in any investigational clinical trial within the last 3 months