Diuretics and Angiotensin-Receptor Blocker Agents in Patients With Stage I Hypertension
Information source: Hospital de Clinicas de Porto Alegre
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Cardiovascular Disease
Intervention: losartan (Drug); Chlorthalidone plus amiloride (Drug)
Phase: Phase 3
Sponsored by: Hospital de Clinicas de Porto Alegre
Official(s) and/or principal investigator(s):
Flávio D Fuchs, MD, PhD, Study Chair, Affiliation: Hospital de Clínicas de Porto Alegre
Sandra C Fuchs, MD, PhD, Phone: 55-5133597621, Email: firstname.lastname@example.org
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.
Official title: A Comparison Between Diuretics and Angiotensin-receptor Blocker Agents in Patients With Stage I Hypertension: PREVER-treatment Study
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Blood pressure variation and proportion of use of add-on drugs
Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
Secondary outcome: fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine
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
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
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?
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.
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
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.
Minimum age: 40 Years.
Maximum age: N/A.
- patients older than 40 years of age with stage I hypertension
- low life expectancy
- other indications for the use of diuretics, such as cardiovascular disease
- intolerance to the study drugs
Locations and Contacts
Sandra C Fuchs, MD, PhD, Phone: 55-5133597621, Email: email@example.com
Hospital de Clínicas de Porto Alegre, UFRGS, Porto Alegre, RS 90035 903, Brazil; Recruiting
Sandra C Fuchs, MD, PhD, Phone: 55 5133597621, Email: firstname.lastname@example.org
Leila B Moreira, MD, PhD, Phone: 55 5133597695, Email: email@example.com
Sandra C Fuchs, MD,PhD, Principal Investigator
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-903, Brazil; Recruiting
Sandra C Fuchs, MD PhD, Phone: 55-51-33598449, Email: firstname.lastname@example.org
Leila B Moreira, MD PhD, Phone: 55-51-33597695, Email: email@example.com
Sandra C Fuchs, MD PhD, Principal Investigator
Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nóbrega AC, Poli-de-Figueiredo CE, Mion D, Bortolotto L, Consolim-Colombo F, Nobre F, Coelho EB, Vilela-Martin JF, Moreno H Jr, Cesarino EJ, Franco R, Brandão AA, de Sousa MR, Pinho Ribeiro AL, Jardim PC, Neto AA, Scala LC, Mota M, Chaves H, Alves JG, Sobral Filho DC, E Silva RP, Figueiredo Neto JA, Irigoyen MC, Castro I, Steffens AA, Schlatter R, de Mello RB, Mosele F, Ghizzoni F, Berwanger O. A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial. Trials. 2011 Feb 24;12:53.
Starting date: July 2010
Last updated: April 20, 2011