Pre-hypertensionPhase 3PREVERNCT00970931
Hypertension Prevention in Pre-Hypertensive Individuals
A Phase 3 study testing Chlorthalidone plus amiloride in people with Pre-hypertension and Hypertension, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
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. Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pre-hypertension, Hypertension, Cardiovascular Disease
- What is being tested?
- Chlorthalidone plus amiloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 730 participants
- Where
- 2 sitesBrazil
- Study dates
- Jul 2010to Sep 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- individuals with 30 to 70 years of age with pre-hypertension
Who cannot join
- low life expectancy
- other indications for the use of diuretics, such as cardiovascular disease
- intolerance to the study drugs
- pregnancy
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital de Clínicas de Porto Alegre, UFRGS
Porto Alegre, Rio Grande do Sul, 90035 903
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
About this study
Official title: Prevention of Hypertension in Patients With Pre-hypertension: PREVER-prevention Study
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.
Read the 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.
- Conditions
- Pre-hypertension, Hypertension, Cardiovascular Disease
- Being tested
- Chlorthalidone plus amiloride, placebo
- Keywords
- hypertension, diuretics
- Medical subject headings
- Prehypertension, Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chlorthalidone plus amilorideDrug
Also called diuretic
Oral Chlorthalidone 12.5 mg plus amiloride 2.5 mg, once a day for 18 months
placeboDrug
Oral placebo once a day, for 18 months
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Not described Receives: Drug: placebo |
| chlortalidone-amiloride | Experimental | Not described Receives: Drug: Chlorthalidone plus amiloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of hypertension, by blood pressure ≥ 140/90 mmHg in individuals without diabetes or ≥ 135/85 mmHg in participants with diabetes.
Measured: 18 months
Adverse events.
Measured: 18 months
Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG
Measured: 18 months
Secondary outcomes (1)
fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2009 (estimated)
- Study startJul 2010
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pre-hypertensionStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 730 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Financiadora de Estudos e Projetos
- Responsible party
- Principal investigator, Flávio Danni Fuchs, Hospital de Clinicas de Porto Alegre
- Investigators
- Flávio D Fuchs, MD, PhD, Study chair, Hospital de Clínics de Porto AlegreSandra C Fuchs, MD, PhD, Study director, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00970931
- Sponsor's protocol ID
- GPPG08621-1
- Acronym
- PREVER
- Status last verified
- Feb 2015
- First submitted
- 2 Sep 2009
- Last updated
- 12 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nobrega 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, Brandao 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.
PubMed 21375762Fuchs FD, Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, Scala LCN, Vilela-Martin JF, Moreira LB, Chaves H, Mota Gomes M, de Sousa MR, Silva RPE, Castro I, Cesarino EJ, Sousa ALL, Alves JG, Steffens AA, Brandao AA, Bortolotto LA, Afiune Neto A, Nobrega AC, Franco RS, Sobral Filho DC, Nobre F, Schlatter R, Gus M, De David CN, Rafaelli L, Sesin GP, Berwanger O, Whelton PK. Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial. J Hypertens. 2018 Apr;36(4):933-938. doi: 10.1097/HJH.0000000000001624.
PubMed 29227377Fuchs 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, Brandao AA, Consolim-Colombo FM, de Alencastro PR, Neto AA, Nobrega 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):e004248. doi: 10.1161/JAHA.116.004248.
PubMed 27965209
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Hypertension in Patients With Pre-hypertension: PREVER-prevention Study
- ClinicalTrials.gov ID
- NCT00970931
- Acronym / sponsor ID
- PREVER / GPPG08621-1
- Conditions
- Pre-hypertension, Hypertension, Cardiovascular Disease
- Keywords
- hypertension, diuretics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 730 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Financiadora de Estudos e Projetos
- Study start
- Jul 2010
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 3 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: placebo |
| chlortalidone-amiloride | Experimental | Drug: Chlorthalidone plus amiloride |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- individuals with 30 to 70 years of age with pre-hypertension
Key exclusion criteria (4 listed)
- low life expectancy
- other indications for the use of diuretics, such as cardiovascular disease
- intolerance to the study drugs
- pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chlorthalidone plus amilorideAlso: diureticOral Chlorthalidone 12.5 mg plus amiloride 2.5 mg, once a day for 18 months | Drug | chlortalidone-amiloride |
| placeboOral placebo once a day, for 18 months | Drug | placebo |
Primary outcome
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
1 secondary outcome
fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2015.
- Background: PubMed 21375762Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nobrega 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, Brandao 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.
- Derived from this study: PubMed 29227377Fuchs FD, Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, Scala LCN, Vilela-Martin JF, Moreira LB, Chaves H, Mota Gomes M, de Sousa MR, Silva RPE, Castro I, Cesarino EJ, Sousa ALL, Alves JG, Steffens AA, Brandao AA, Bortolotto LA, Afiune Neto A, Nobrega AC, Franco RS, Sobral Filho DC, Nobre F, Schlatter R, Gus M, De David CN, Rafaelli L, Sesin GP, Berwanger O, Whelton PK. Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial. J Hypertens. 2018 Apr;36(4):933-938. doi: 10.1097/HJH.0000000000001624.
- Derived from this study: PubMed 27965209Fuchs 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, Brandao AA, Consolim-Colombo FM, de Alencastro PR, Neto AA, Nobrega 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):e004248. doi: 10.1161/JAHA.116.004248.
Related trials for Pre-hypertension
RecruitingObservational study
Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Preeclampsia
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
RecruitingPhase 3
A Study of Orforglipron in Participants With Overweight at Risk of Development of Obesity-Related Complications or Progression to Class 1 Obesity
Overweight, Prediabetic State
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruitingPhase 2
Furosemide vs Placebo in Severe Preeclampsia Postpartum
Severe Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flávio D Fuchs, MD, PhD study chair
Hospital de Clínics de Porto Alegre
Sandra C Fuchs, MD, PhD study director
Hospital de Clinicas de Porto Alegre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chlorthalidone plus amiloride in people with Pre-hypertension and Hypertension, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00970931, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2015.