Diuretics and Angiotensin-Receptor Blocker Agents in Patients With Stage I Hypertension (PREVER)

February 11, 2015 updated by: Flávio Danni Fuchs, Hospital de Clinicas de Porto Alegre

A Comparison Between Diuretics and Angiotensin-receptor Blocker Agents in Patients With Stage I Hypertension: PREVER-treatment Study

High blood pressure is the major risk factor for Cardiovascular disease (CVD). The prevalence of hypertension in Brazil was established in population-based studies conducted in different cities and States, varying from 22.3 to 44% of adults.

The benefit of drug treatment of hypertension to prevent major cardiovascular events was consistently demonstrated in a large series of clinical trials controlled by placebo.

Diuretics are at least as efficacious as other blood pressure-lowering drugs, are well tolerated, have longer duration of action and the advantage of very low cost to be used in a population intervention. Chlorthalidone is the more efficacious agent. Its main limitation is to induce hypokalemia in a proportion of patients, an adverse effect that can be antagonized by a potassium-sparing diuretic, as amiloride.

A study comparing diuretic with an ARB agent is therefore recommendable in Brazil, in order to support the decisions of the Health Secretary in regard to blood pressure agents supply for the Brazilian population. Such a study was demanded and funded by the Health and Technology Ministries in Brazil.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cardiovascular disease (CVD) is already the leading cause of death in Brazil. The superiority of any particular agent among the groups of blood pressure-lowering drugs was investigated in various clinical trials. ALLHAT, the largest and better designed trial showed that chlorthalidone had similar efficacy to prevent fatal and non-fatal coronary events as an ACE inhibitor (lisinopril) and a calcium channel blocker agent (amlodipine). Chlorthalidone was superior to the other agents in the prevention of other cardiovascular outcomes, particularly heart failure. Amlodipine was superior to valsartan, an angiotensin-receptor blocker (ARB) agent, in the prevention of CHD and stroke. There is no head-to-head comparison between diuretics and ARB agents in the prevention of hard cardiovascular outcomes, and even the comparison of their blood pressure-lowering effects is scarcely described in the literature. Despite this, ARB agents are the leading brands in terms of profits in various countries in the world, including Brazil. This leadership is based on a strong commercial strategy, which includes the distortion of the evidences of clinical trials in favor of these drugs. The idea that they have blood pressure-independent effects is accepted by most, despite the evidences of better designed trials. The option by an ARB agent instead of a diuretic as the first line option in the public health system in Brazil would result in a large expenditure of resources, and there is a pressure to include them in the list of essential drugs provided by the government.

This is a nation-based trial, with 24 clinical centers distributed in 9 States. A Coordinating Committee is responsible for the elaboration of this proposal and for the main decisions of the trial. The organizational chart of the study will include an executive Committee, a safety committee, outcome committee, lab and EKG centers, and the research units.

Research questions

  1. Is losartan more efficacious and safe than the association of chlorthalidone with amiloride as the first option to control blood pressure in patients with stage I hypertension?
  2. Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the development of target-organ damage in patients with stage I hypertension?
  3. Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the occurrence of major cardiovascular events in patients with stage I hypertension?

Methods

Design: randomized, double-blind, clinical trial, controlled by an active treatment.

Eligible participants: patients older than 40 years of age with Stage I hypertension.

Exclusion criteria: low life expectancy, other indications for the use of diuretics, such as cardiovascular disease, intolerance to the study drugs, pregnancy.

Random allocation: by a computer generated list, stratified by center.

Interventions: Chlorthalidone plus amiloride up to 25 e 5 mg daily, versus losartan up to 100 mg daily. Amlodipine up to 10 mg daily and propranolol up to 160 mg/dia, in an open fashion, will be added if blood pressure is not controlled.

Outcomes:

Primary:

  1. Blood pressure variation and proportion of use of add-on drugs.
  2. Adverse events.
  3. Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.

Secondary: fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine.

Follow-up and duration of the study: consultations for evaluation and enrollment and thereafter consultations at the 3th., 6th., 9th, 12th. and 18th. months.

Study Type

Interventional

Enrollment (Actual)

655

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • RS
      • Porto Alegre, RS, Brazil, 90035-903
        • Hospital de Clínicas de Porto Alegre
      • Porto Alegre, RS, Brazil, 90035 903
        • Hospital de Clínicas de Porto Alegre, UFRGS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients older than 40 years of age with stage I hypertension

Exclusion Criteria:

  • low life expectancy
  • other indications for the use of diuretics, such as cardiovascular disease
  • intolerance to the study drugs
  • pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Chlorthalidone plus amiloride
Oral Chlorthalidone plus amiloride up to 25 e 5 mg daily for 18 months
Drug: Chlorthalidone plus amiloride
Oral Chlorthalidone plus amiloride up to 25 e 5 mg daily, once a day for 18 months
Other Names:
  • diuretics
Experimental: losartan
Oral losartan up to 100 mg daily, once a day, for 18 month
Drug: losartan
Oral losartan up to 100 mg daily fo 18 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Blood pressure variation and proportion of use of add-on drugs
Time Frame: 18 months
18 months
Adverse events
Time Frame: 18 months
18 months
Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
Time Frame: 18 monyhs
18 monyhs

Secondary Outcome Measures

Outcome Measure
Time Frame
fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine
Time Frame: 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital de Clinicas de Porto Alegre

Collaborators

Financiadora de Estudos e Projetos

Investigators

  • Study Chair: Flávio D Fuchs, MD, PhD, Hospital de Clínicas de Porto Alegre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

September 2, 2009

First Submitted That Met QC Criteria

September 2, 2009

First Posted (Estimate)

September 3, 2009

Study Record Updates

Last Update Posted (Estimate)

February 12, 2015

Last Update Submitted That Met QC Criteria

February 11, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GPPG08621-2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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