Hypertension Prevention in Pre-Hypertensive Individuals

Hypertension Clinical Trial

— PREVER  

Official title:

Prevention of Hypertension in Patients With Pre-hypertension: PREVER-prevention Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00970931
• Other study ID #: GPPG08621-1
• Status: Completed
• Phase: Phase 3
• First received: September 2, 2009
• Last updated: February 11, 2015
• Start date: July 2010
• Est. completion date: September 2014

Study information

• Verified date: February 2015
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 730
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Hypertension
• Pre-hypertension
• Prehypertension

Intervention

Drug:
• Chlorthalidone plus amiloride
Oral Chlorthalidone 12.5 mg plus amiloride 2.5 mg, once a day for 18 months
• placebo
Oral placebo once a day, for 18 months

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS
Brazil	Hospital de Clínicas de Porto Alegre, UFRGS	Porto Alegre	RS

Sponsors (2)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Financiadora de Estudos e Projetos

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nóbrega AC, Poli-de-Figueiredo CE, Mion D, Bortoloto L, Consolim-Colombo F, Nobre F, Coelho EB, Vilela-Martin JF, Moreno H Jr, Cesarino EJ, Franco R, Brandão AA, de Sousa MR, Ribeiro AL, Jardim PC, Neto AA, Scala LC, Mota M, Chaves H, Alves JG, Filho DC, Pereira e Silva R, Neto JA, Irigoyen MC, Castro I, Steffens AA, Schlatter R, de Mello RB, Mosele F, Ghizzoni F, Berwanger O. Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial. Trials. 2011 Mar 5;12:65. doi: 10.1186/1745-6215-12-65. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of hypertension, by blood pressure = 140/90 mmHg in individuals without diabetes or = 135/85 mmHg in participants with diabetes.		18 months	No
Primary	Adverse events.		18 months	Yes
Primary	Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG		18 months	No
Secondary	fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine		18 months	No