HypertensionPhase 3PREVERNCT00971165
Diuretics and Angiotensin-Receptor Blocker Agents in Patients With Stage I Hypertension
A Phase 3 study testing losartan and Chlorthalidone plus amiloride in people with Hypertension and Cardiovascular Disease, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
Trial summary
High blood pressure is the major risk factor for Cardiovascular disease (CVD). 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Hypertension, Cardiovascular Disease
- What is being tested?
- losartan and Chlorthalidone plus amiloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 655 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients older than 40 years of age with stage I 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: A Comparison Between Diuretics and Angiotensin-receptor Blocker Agents in Patients With Stage I Hypertension: PREVER-treatment Study
High blood pressure is the major risk factor for Cardiovascular disease (CVD). 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 drug treatment of hypertension to prevent major cardiovascular events was consistently demonstrated in a large series of clinical trials controlled by placebo.
Read more
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 comparing diuretic with an ARB agent is therefore recommendable in Brazil, in order to support the decisions of the Health Secretary in regard to blood pressure agents supply for the Brazilian population. Such a study was demanded and funded by the Health and Technology Ministries in Brazil.
Read the detailed description
Cardiovascular disease (CVD) is already the leading cause of death in Brazil. The superiority of any particular agent among the groups of blood pressure-lowering drugs was investigated in various clinical trials. ALLHAT, the largest and better designed trial showed that chlorthalidone had similar efficacy to prevent fatal and non-fatal coronary events as an ACE inhibitor (lisinopril) and a calcium channel blocker agent (amlodipine). Chlorthalidone was superior to the other agents in the prevention of other cardiovascular outcomes, particularly heart failure. Amlodipine was superior to valsartan, an angiotensin-receptor blocker (ARB) agent, in the prevention of CHD and stroke. There is no head-to-head comparison between diuretics and ARB agents in the prevention of hard cardiovascular outcomes, and even the comparison of their blood pressure-lowering effects is scarcely described in the literature. Despite this, ARB agents are the leading brands in terms of profits in various countries in the world, including Brazil. This leadership is based on a strong commercial strategy, which includes the distortion of the evidences of clinical trials in favor of these drugs. The idea that they have blood pressure-independent effects is accepted by most, despite the evidences of better designed trials. The option by an ARB agent instead of a diuretic as the first line option in the public health system in Brazil would result in a large expenditure of resources, and there is a pressure to include them in the list of essential drugs provided by the government.
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.
Research questions
- Is losartan more efficacious and safe than the association of chlorthalidone with amiloride as the first option to control blood pressure in patients with stage I hypertension?
- Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the development of target-organ damage in patients with stage I hypertension?
- Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the occurrence of major cardiovascular events in patients with stage I hypertension?
Methods
Design: randomized, double-blind, clinical trial, controlled by an active treatment.
Eligible participants: patients older than 40 years of age with Stage I 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 plus amiloride up to 25 e 5 mg daily, versus losartan up to 100 mg daily. Amlodipine up to 10 mg daily and propranolol up to 160 mg/dia, in an open fashion, will be added if blood pressure is not controlled.
Outcomes:
Primary:
- Blood pressure variation and proportion of use of add-on drugs.
- Adverse events.
- Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
Secondary: fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine.
Follow-up and duration of the study: consultations for evaluation and enrollment and thereafter consultations at the 3th., 6th., 9th, 12th. and 18th. months.
- Conditions
- Hypertension, Cardiovascular Disease
- Being tested
- losartan, Chlorthalidone plus amiloride
- Keywords
- Hypertension, Chlorthalidone, Amiloride, Losartan, treatment
- Medical subject headings
- Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
losartanDrug
Oral losartan up to 100 mg daily fo 18 months
Chlorthalidone plus amilorideDrug
Also called diuretics
Oral Chlorthalidone plus amiloride up to 25 e 5 mg daily, once a day for 18 months
| Study group | Role | What they receive |
|---|---|---|
| Chlorthalidone plus amiloride | Active comparator | Oral Chlorthalidone plus amiloride up to 25 e 5 mg daily for 18 months Receives: Drug: Chlorthalidone plus amiloride |
| losartan | Experimental | Oral losartan up to 100 mg daily, once a day, for 18 month Receives: Drug: losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood pressure variation and proportion of use of add-on drugs
Measured: 18 months
Adverse events
Measured: 18 months
Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
Measured: 18 monyhs
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 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 655 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 Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00971165
- Sponsor's protocol ID
- GPPG08621-2
- 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, Bortolotto 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, Afiune Neto A, Scala LC, Mota M, Chaves H, Alves JG, Sobral Filho DC, Pereira e Silva R, Figueiredo Neto JA, Irigoyen MC, Castro I, Steffens AA, Schlatter R, de Mello RB, Mosele F, Ghizzoni F, Berwanger O. A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial. Trials. 2011 Feb 24;12:53. doi: 10.1186/1745-6215-12-53.
PubMed 21349192Fuchs FD, Scala LCN, Vilela-Martin JF, Whelton PK, Poli-de-Figueiredo CE, Pereira E Silva R, Gus M, Bortolotto LA, Consolim-Colombo FM, Schlatter RP, Cesarino JE, Castro I, Figueiredo Neto JA, Chaves H, Steffens AA, Alves JG, Brandao AA, de Sousa MR, Jardim PC, Moreira LB, Franco RS, Gomes MM, Afiune Neto A, Fuchs FC, Sobral Filho DC, Nobrega AC, Nobre F, Berwanger O, Fuchs SC. Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial. Acta Diabetol. 2021 Feb;58(2):215-220. doi: 10.1007/s00592-020-01611-8. Epub 2020 Oct 13.
PubMed 33047257Fuchs FD, Scala LC, Vilela-Martin JF, de Mello RB, Mosele F, Whelton PK, Poli-de-Figueiredo CE, de Alencastro PR, E Silva RP, Gus M, Bortolotto LA, Schlatter R, Cesarino EJ, Castro I, Neto JA, Chaves H, Steffens AA, Alves JG, Brandao AA, de Sousa MR, Jardim PC, Moreira LB, Franco RS, Gomes MM, Neto AA, Fuchs FC, Filho DC, Nobrega AC, Nobre F, Berwanger O, Fuchs SC. Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial. J Hypertens. 2016 Apr;34(4):798-806. doi: 10.1097/HJH.0000000000000837.
PubMed 26938814
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
- A Comparison Between Diuretics and Angiotensin-receptor Blocker Agents in Patients With Stage I Hypertension: PREVER-treatment Study
- ClinicalTrials.gov ID
- NCT00971165
- Acronym / sponsor ID
- PREVER / GPPG08621-2
- Conditions
- Hypertension, Cardiovascular Disease
- Keywords
- Hypertension, Chlorthalidone, Amiloride, Losartan, treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 655 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.
High blood pressure is the major risk factor for Cardiovascular disease (CVD). 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 drug treatment of hypertension to prevent major cardiovascular events was consistently demonstrated in a large series of clinical trials controlled by placebo.
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 comparing diuretic with an ARB agent is therefore recommendable in Brazil, in order to support the decisions of the Health Secretary in regard to blood pressure agents supply for the Brazilian population. Such a study was demanded and funded by the Health and Technology Ministries in Brazil.
Detailed description
Cardiovascular disease (CVD) is already the leading cause of death in Brazil. The superiority of any particular agent among the groups of blood pressure-lowering drugs was investigated in various clinical trials. ALLHAT, the largest and better designed trial showed that chlorthalidone had similar efficacy to prevent fatal and non-fatal coronary events as an ACE inhibitor (lisinopril) and a calcium channel blocker agent (amlodipine). Chlorthalidone was superior to the other agents in the prevention of other cardiovascular outcomes, particularly heart failure. Amlodipine was superior to valsartan, an angiotensin-receptor blocker (ARB) agent, in the prevention of CHD and stroke. There is no head-to-head comparison between diuretics and ARB agents in the prevention of hard cardiovascular outcomes, and even the comparison of their blood pressure-lowering effects is scarcely described in the literature. Despite this, ARB agents are the leading brands in terms of profits in various countries in the world, including Brazil. This leadership is based on a strong commercial strategy, which includes the distortion of the evidences of clinical trials in favor of these drugs. The idea that they have blood pressure-independent effects is accepted by most, despite the evidences of better designed trials. The option by an ARB agent instead of a diuretic as the first line option in the public health system in Brazil would result in a large expenditure of resources, and there is a pressure to include them in the list of essential drugs provided by the government.
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.
Research questions
- Is losartan more efficacious and safe than the association of chlorthalidone with amiloride as the first option to control blood pressure in patients with stage I hypertension?
- Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the development of target-organ damage in patients with stage I hypertension?
- Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the occurrence of major cardiovascular events in patients with stage I hypertension?
Methods
Design: randomized, double-blind, clinical trial, controlled by an active treatment.
Eligible participants: patients older than 40 years of age with Stage I 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 plus amiloride up to 25 e 5 mg daily, versus losartan up to 100 mg daily. Amlodipine up to 10 mg daily and propranolol up to 160 mg/dia, in an open fashion, will be added if blood pressure is not controlled.
Outcomes:
Primary:
- Blood pressure variation and proportion of use of add-on drugs.
- Adverse events.
- Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.
Secondary: fatal or major cardiovascular events: myocardial infarction, stroke, coronary interventions, heart failure, duplication of creatinine.
Follow-up and duration of the study: consultations for evaluation and enrollment and thereafter consultations at the 3th., 6th., 9th, 12th. and 18th. months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chlorthalidone plus amiloride | Active comparator | Drug: Chlorthalidone plus amilorideOral Chlorthalidone plus amiloride up to 25 e 5 mg daily for 18 months |
| losartan | Experimental | Drug: losartanOral losartan up to 100 mg daily, once a day, for 18 month |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients older than 40 years of age with stage I 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 |
|---|---|---|
| losartanOral losartan up to 100 mg daily fo 18 months | Drug | losartan |
| Chlorthalidone plus amilorideAlso: diureticsOral Chlorthalidone plus amiloride up to 25 e 5 mg daily, once a day for 18 months | Drug | Chlorthalidone plus amiloride |
Primary outcome
Blood pressure variation and proportion of use of add-on drugs
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 monyhs
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 21349192Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nobrega AC, Poli-de-Figueiredo CE, Mion D, Bortolotto 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, Afiune Neto A, Scala LC, Mota M, Chaves H, Alves JG, Sobral Filho DC, Pereira e Silva R, Figueiredo Neto JA, Irigoyen MC, Castro I, Steffens AA, Schlatter R, de Mello RB, Mosele F, Ghizzoni F, Berwanger O. A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial. Trials. 2011 Feb 24;12:53. doi: 10.1186/1745-6215-12-53.
- Derived from this study: PubMed 33047257Fuchs FD, Scala LCN, Vilela-Martin JF, Whelton PK, Poli-de-Figueiredo CE, Pereira E Silva R, Gus M, Bortolotto LA, Consolim-Colombo FM, Schlatter RP, Cesarino JE, Castro I, Figueiredo Neto JA, Chaves H, Steffens AA, Alves JG, Brandao AA, de Sousa MR, Jardim PC, Moreira LB, Franco RS, Gomes MM, Afiune Neto A, Fuchs FC, Sobral Filho DC, Nobrega AC, Nobre F, Berwanger O, Fuchs SC. Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial. Acta Diabetol. 2021 Feb;58(2):215-220. doi: 10.1007/s00592-020-01611-8. Epub 2020 Oct 13.
- Derived from this study: PubMed 26938814Fuchs FD, Scala LC, Vilela-Martin JF, de Mello RB, Mosele F, Whelton PK, Poli-de-Figueiredo CE, de Alencastro PR, E Silva RP, Gus M, Bortolotto LA, Schlatter R, Cesarino EJ, Castro I, Neto JA, Chaves H, Steffens AA, Alves JG, Brandao AA, de Sousa MR, Jardim PC, Moreira LB, Franco RS, Gomes MM, Neto AA, Fuchs FC, Filho DC, Nobrega AC, Nobre F, Berwanger O, Fuchs SC. Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial. J Hypertens. 2016 Apr;34(4):798-806. doi: 10.1097/HJH.0000000000000837.
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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 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 losartan and Chlorthalidone plus amiloride in people with Hypertension and Cardiovascular Disease, 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. 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?
Blood pressure variation and proportion of use of add-on drugs (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 NCT00971165, 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.