Hypertension Prevention in Pre-Hypertensive Individuals (PREVER)

Tracking Information
First Submitted Date ICMJE	September 2, 2009
First Posted Date ICMJE	September 3, 2009
Last Update Posted Date	February 12, 2015
Study Start Date ICMJE	July 2010
Actual Primary Completion Date	September 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 2, 2009)	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 ]; Adverse events. [ Time Frame: 18 months ]; Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG [ Time Frame: 18 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00970931 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 2, 2009)	fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine [ Time Frame: 18 months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Hypertension Prevention in Pre-Hypertensive Individuals
Official Title ICMJE	Prevention of Hypertension in Patients With Pre-hypertension: PREVER-prevention Study
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; Does an association of low doses of chlorthalidone and amiloride reduce the incidence of hypertension in individuals with pre-hypertension?; Does an association of low doses of chlorthalidone and amiloride reduce the incidence of cardiovascular events in patients with pre-hypertension?; 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: Incidence of hypertension, by blood pressure ≥ 140/90 mmHg in individuals without diabetes or ≥ 135/85 mmHg in participants with diabetes.; Adverse events.; Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition ICMJE	Pre-hypertension; Hypertension; Cardiovascular Disease
Intervention ICMJE	Drug: Chlorthalidone plus amiloride Oral Chlorthalidone 12.5 mg plus amiloride 2.5 mg, once a day for 18 months Other Name: diuretic; Drug: placebo Oral placebo once a day, for 18 months
Study Arms	Placebo Comparator: placebo Intervention: Drug: placebo; Experimental: chlortalidone-amiloride Intervention: Drug: Chlorthalidone plus amiloride
Publications *	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.; Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, Scala LC, Whelton PK, Mosele F, de Mello RB, Vilela-Martin JF, Moreira LB, Chaves H, Mota Gomes M, de Sousa MR, Silva RP, Castro I, Cesarino EJ, Jardim PC, Alves JG, Steffens AA, Brandão AA, Consolim-Colombo FM, de Alencastro PR, Neto AA, Nóbrega AC, Franco RS, Sobral Filho DC, Bordignon A, Nobre F, Schlatter R, Gus M, Fuchs FC, Berwanger O, Fuchs FD. Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial. J Am Heart Assoc. 2016 Dec 13;5(12). pii: e004248.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 11, 2015)	730
Original Estimated Enrollment ICMJE; (submitted: September 2, 2009)	1250
Actual Study Completion Date	September 2014
Actual Primary Completion Date	September 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	30 Years to 70 Years (Adult, Senior)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Brazil
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00970931
Other Study ID Numbers ICMJE	GPPG08621-1
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Flávio Danni Fuchs, Hospital de Clinicas de Porto Alegre
Study Sponsor ICMJE	Hospital de Clinicas de Porto Alegre
Collaborators ICMJE	Financiadora de Estudos e Projetos
Investigators ICMJE	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
PRS Account	Hospital de Clinicas de Porto Alegre
Verification Date	February 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP