Hypertension Prevention in Pre-Hypertensive Individuals
Condition: Pre-hypertension; Hypertension; Cardiovascular Disease
MeSH terms: Hypertension; Cardiovascular Diseases; Prehypertension
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Chlorthalidone plus amiloride; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral Chlorthalidone 12.5 mg plus amiloride 2.5 mg, once a day for 18 months; Oral placebo once a day, for 18 months
Other intervention name(s): diuretic
Intervention MeSH terms: Chlorthalidone; Amiloride; Diuretics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: hypertension; diuretics