Prevention of Diabetes and Hypertension (PHIDIAS)

This study has been terminated.
(Because of delay in approval of the protocol by a number of Ethics Commitees the trial was terminated on March 4, 2010. No patient had received any study drug.)
Sponsor:
Collaborators:
Italian Society of Hypertension
Italian Society of General Practitioners
Yghea
Information provided by:
Istituto Auxologico Italiano
ClinicalTrials.gov Identifier:
NCT00456963
First received: April 4, 2007
Last updated: July 4, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Hypertension
Behavioral: Diet
Behavioral: Moderate exercise
Drug: enalapril tablets
Drug: placebo tablets
Drug: Losartan Tablets
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Prevention of Hypertension Incidence and Diabetes Italian Assessment Study. Therapeutic Strategies of Prevention of Diabetes and Hypertension in Subjects With Metabolic Syndrome and High-Normal Blood Pressure.

Resource links provided by NLM:


Further study details as provided by Istituto Auxologico Italiano:

Primary Outcome Measures:
  • Time to first event of: new diabetes or initiation of any antidiabetic treatment during the treatment period of the trial [ Designated as safety issue: No ]
  • new hypertension or initiation of any antihypertensive treatment during the treatment period of the trial. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first event (during the treatment phase) of: new diabetes or new hypertension, which comes first [ Designated as safety issue: No ]
  • major cardiovascular events (myocardial infarction, stroke, cardiovascular death, heart failure, new documented angina, [ Designated as safety issue: No ]
  • revascularization procedures ) plus death by non-cardiovascular causes [ Designated as safety issue: No ]
  • variations of SBP and DBP during the treatment phase and, separately, during the withdrawal phase [ Designated as safety issue: No ]
  • variations fasting blood glucose during the treatment phase and, separately, during the withdrawal phase [ Designated as safety issue: No ]
  • estimated creatinine clearance lower than 60 ml/min in subjects with values >= 60 ml/min at baseline [ Designated as safety issue: No ]
  • serious adverse effects. Incidence at the end of the final 6-month withdrawal phase of:new diabetes [ Designated as safety issue: No ]
  • new hypertension [ Designated as safety issue: No ]
  • variations of SBP and DBP [ Designated as safety issue: No ]
  • variations of fasting blood glucose. [ Designated as safety issue: No ]

Estimated Enrollment: 3000
Study Start Date: September 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diet, exercise and Enalapril
one Enalapril 10mg tablet and one Losartan placebo tablet once daily for four weeks. Subsequentely one Enalapril 20mg tablet and one Losartan placebo tablet once daily until the end of the randomized treatment phase. After this one Enalapril placebo tablet and one Losartan placebo tablet once daily for six months.
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
Active Comparator: Diet, Exercise and Losartan
one Losartan 50mg tablet and one Enalapril placebo tablet once daily for four weeks. Subsequentely one Losartan 100mg tablet and one Enalapril placebo tablet once daily until the end of the randomized treatment phase. After this one Losartan placebo tablet and one Enalapril placebo tablet once daily for six months.
Behavioral: Diet
total fat < 5%, saturated fat < 10%, vegetables, fruit
Behavioral: Moderate exercise
30 min at least 5 times/week
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.
Placebo Comparator: Diet, exercise and Placebo
one Enalapril placebo tablet and one Losartan placebo tablet once daily until study end.
Behavioral: Diet
total fat < 5%, saturated fat < 10%, vegetables, fruit
Behavioral: Moderate exercise
30 min at least 5 times/week
Drug: placebo tablets
one Enalapril placebo tablet and one Losartan placebo tablet once daily until study end.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00456963

Locations
Italy
Istituto Auxologico Italiano.
Milan, Italy, 20145
Sponsors and Collaborators
Istituto Auxologico Italiano
Italian Society of Hypertension
Italian Society of General Practitioners
Yghea
Investigators
Principal Investigator: Alberto Zanchetti, MD Istituto Auxologico Italiano. Milan. Italy
  More Information

Publications:

Responsible Party: Professor Alberto Zanchetti, Istituto Auxologico Italiano
ClinicalTrials.gov Identifier: NCT00456963     History of Changes
Other Study ID Numbers: FARM5JYE9K
Study First Received: April 4, 2007
Last Updated: July 4, 2011
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Istituto Auxologico Italiano:
angiotensin converting enzyme inhibitors
angiotensin receptor blockers
diabetes
hypertension
therapeutic strategies

Additional relevant MeSH terms:
Hypertension
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Enalapril
Enalaprilat
Losartan
Angiotensin Receptor Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers

ClinicalTrials.gov processed this record on August 28, 2014