Hypertension Prevention in Pre-Hypertensive Individuals (PREVER)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
FINEP
Information provided by (Responsible Party):
Flávio Danni Fuchs, Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier:
NCT00970931
First received: September 2, 2009
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

The incidence of hypertension in individuals with pre-hypertension was 80% in ten years in a study conducted in Southern Brazil. The effectiveness of non-drug interventions to prevent hypertension is low in the long term. It may be hypothesized that a population-based drug intervention could reduce relevantly the burden of hypertension and cardiovascular disease.

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 with this objective is therefore recommendable in Brazil, in order to support a plan of precocious intervention in individuals with pre-hypertension. Such a study was demanded and funded by the Health and Technology Ministries in Brazil.


Condition Intervention Phase
Pre-hypertension
Hypertension
Cardiovascular Disease
Drug: Chlorthalidone plus amiloride
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Hypertension in Patients With Pre-hypertension: PREVER-prevention Study

Resource links provided by NLM:


Further study details as provided by Hospital de Clinicas de Porto Alegre:

Primary Outcome Measures:
  • Incidence of hypertension, by blood pressure ≥ 140/90 mmHg in individuals without diabetes or ≥ 135/85 mmHg in participants with diabetes. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Adverse events. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 1250
Study Start Date: July 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo Drug: placebo
Oral placebo once a day, for 18 months
Experimental: chlortalidone-amiloride Drug: Chlorthalidone plus amiloride
Oral Chlorthalidone 12.5 mg plus amiloride 2.5 mg, once a day for 18 months
Other Name: diuretic

Detailed Description:

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 Cardiovascular disease (CVD) is already the leading cause of death in Brazil. High blood pressure is the major risk factor for CVD. The risks start at blood pressure values as lower as 115/75 mmHg but increase exponentially and confer higher absolute risks with blood pressure higher than 140/90 mmHg. 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 treatment of individuals with pre-hypertension and cardiovascular disease was demonstrated in several clinical trials. In face of the higher incidence of hypertension in individuals with pre-hypertension, the low effectiveness of non-drug interventions and the risks for cardiovascular events and end-organ damage at lower blood pressure levels, it may be advisable to start blood pressure drugs at low doses at this point of the inexorable elevation of blood pressure with aging.

Research questions

  1. Does an association of low doses of chlorthalidone and amiloride reduce the incidence of hypertension in individuals with pre-hypertension?
  2. Does an association of low doses of chlorthalidone and amiloride reduce the incidence of cardiovascular events in patients with pre-hypertension?
  3. 2. Does an association of low doses of chlorthalidone and amiloride reduce the incidence of target-organ damage in patients with pre-hypertension?

Methods

Design: randomized, double-blind, clinical trial, controlled by placebo.

Eligible participants: individuals with 30 to 70 years of age with pre-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 12.5 mg plus amiloride 2.5 mg or identical placebo.

Primary outcomes:

  1. Incidence of hypertension, by blood pressure ≥ 140/90 mmHg in individuals without diabetes or ≥ 135/85 mmHg in participants with diabetes.
  2. Adverse events.
  3. Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • individuals with 30 to 70 years of age with pre-hypertension

Exclusion Criteria:

  • low life expectancy
  • other indications for the use of diuretics, such as cardiovascular disease
  • intolerance to the study drugs
  • pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00970931

Locations
Brazil
Hospital de Clínicas de Porto Alegre, UFRGS
Porto Alegre, RS, Brazil, 90035 903
Hospital de Clínicas de Porto Alegre
Porto Alegre, RS, Brazil, 90035-903
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
FINEP
Investigators
Study Chair: Flávio D Fuchs, MD, PhD Hospital de Clínics de Porto Alegre
Study Director: Sandra C Fuchs, MD, PhD Hospital de Clínicas de Porto Alegre
  More Information

No publications provided by Hospital de Clinicas de Porto Alegre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Flávio Danni Fuchs, Dr., Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier: NCT00970931     History of Changes
Other Study ID Numbers: GPPG08621-1
Study First Received: September 2, 2009
Last Updated: December 2, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Hospital de Clinicas de Porto Alegre:
hypertension
diuretics

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Prehypertension
Vascular Diseases
Amiloride
Chlorthalidone
Diuretics
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Antihypertensive Agents

ClinicalTrials.gov processed this record on April 23, 2014