Hypertension Prevention in Pre-Hypertensive Individuals

Phase 3

Completed

• Conditions: Pre-hypertension; Cardiovascular Disease; Hypertension
• Interventions: Drug: placebo; Drug: Chlorthalidone plus amiloride

• Registration Number: NCT00970931
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2009-09-02
• Study First Submitted QC: 2009-09-02
• Study First Posted: 2009-09-03
• Study Start: 2010-07
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Status Verified: 2015-02
• Last Update Submitted: 2015-02-11
• Last Update Posted: 2015-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 730

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	-
chlortalidone-amiloride	Chlorthalidone plus amiloride	-

Primary Outcome Measures

Name	Time	Method
Incidence of hypertension, by blood pressure ≥ 140/90 mmHg in individuals without diabetes or ≥ 135/85 mmHg in participants with diabetes.	18 months
Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG	18 months
Adverse events.	18 months

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Hospital de Clínicas de Porto Alegre, UFRGS; 🇧🇷 Porto Alegre, RS, Brazil

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil