PHARES Study: Management of Resistant Hypertension

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Study Completion Date

2009-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to assess the efficacy of two different treatment regimens for treating resistant hypertension previously uncontrolled with at least 3 antihypertensive treatments. The study hypothesis is that these two regimens (one based on increasing diuretics and the other based on increasing renin angiotensin system blockage) may not differ in terms of efficacy.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Tested hypothesis: For essential resistant hypertension, a new regimen based on intensive RAS blockage is non inferior to the recommended regimen based on intensive sodium depletion.

Primary objective: To demonstrate non-inferiority (i.e difference between the two regimen less than 5 mmHg for the mean day-time SBP at week 12)

* One treatment arm including irbesartan 300 mg, hydrochlorothiazide (HCTZ) 12.5mg, amlodipine 5 mg, ramipril 10mg and bisoprolol 10 mg
* One treatment arm including irbesartan 300 mg, HCTZ 12.5mg, amlodipine 5 mg, spironolactone 25 mg, furosemide 40 mg and amiloride 5 mg.

Secondary objectives:

* To assess clinical and biological safety and efficacy of these regimen
* To evaluate predicted factors of controlled or uncontrolled BP
* To evaluate compliance to treatment
* To compare the cost of the different strategies
* To compare the two strategies in terms of endothelial function and left ventricular diastolic filling

Study design:

* Period 1 from week-4 to week 0 : 4-week treatment for all patients with irbesartan 300 mg, HCTZ 12.5mg, amlodipine 5 mg. At the end of this period, an ABPM will be performed: only patients with a mean day time SBP\>135 and/or DBP\>85 mmHg will be randomized for a further 3 months treatment
* Period 2 from week 0 to week 4: patients will be randomized in two groups, the first one receiving spironolactone 25mg and the second one receiving ramipril 5 mg as add-on therapy (on top of the previous tri-therapy).
* Period 3 from week 4 to week 8: Patients with BP controlled at week 4 (i.e mean home blood pressure measurement (HBPM) \<135/85 mmHg at week 4) remain on the same treatment. For those uncontrolled (i.e. mean HBPM \>135/85 mmHg at week 4), furosemide 20 mg will be added in the first group and ramipril will be titrated to 10 mg in the second group
* Period 4 from week 8 to week 10: Patients with BP controlled at week 8 (i.e. mean HBPM \<135/85 mmHg at week 8) remain on the same treatment. For those uncontrolled (i.e. mean HBPM \>135/85 mmHg at week 8), furosemide will be titrated to 40 mg in the first group and bisoprolol 5 mg will be added in the second group.
* Period 5 from week 10 to week 12 (end of the study): Patients with BP controlled at week 10 (i.e mean HBPM \<135/85 mmHg at week 10) remain on the same treatment. For those uncontrolled (i.e mean HBPM \> 135/85 mmHg at week 10), amiloride 5 mg will be added to the previous treatment in the first group and bisoprolol will be titrated to 10 mg in the second group.

Reasons for treatment discontinuation:

* Patient decision
* Informed consent withdrawal
* SBP\>180 mmHg or \<100 mmHg (HBPM) whatever the time during the trial
* Adverse events related to treatment or not

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypertension

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Resistant hypertension Combined diuretic therapy Combined RAS blockers

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

irbesartan, amlodipine and hydrochlorothiazide

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Primary hypertension
* Resistant hypertension defined by mean day-time SBP \> 135 mmHg and DBP \> 85 mmHg (determined with ABPM device) after a standardized 4-week regimen including irbesartan, amlodipine and HCTZ.

Exclusion Criteria

* Secondary hypertension
* Unstable angina, history of stroke or coronary heart disease (coronary by-pass or angioplasty) in the previous 3 months
* History of cough with ACEi or gynecomastia with antialdosterones
* Heart failure (New York Heart Association \[NYHA\] III-IV)
* Contraindication to beta blockers because of bronchopathy or auriculoventricular block
* Diabetes mellitus (type 1 or 2) with HbA1C \> 8%
* Renal failure with creatinine clearance \< 40ml/min (COCKROFT evaluation)
* Arm circumference \> 42 cm

Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Department of Clinical Research of developpement

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Guillaume BOBRIE, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Investigation Clinical Center European Georges Pompidou Hospital

Paris, Île-de-France Region, France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

Mendes M, Dubourg J, Blanchard A, Bergerot D, Courand PY, Forni V, Frank M, Bobrie G, Menard J, Azizi M. Copeptin is increased in resistant hypertension. J Hypertens. 2016 Dec;34(12):2458-2464. doi: 10.1097/HJH.0000000000001106.

Reference Type DERIVED

PMID: 27755389 (View on PubMed)

Frank M, Peyrard S, Bobrie G, Azizi M. Method of mean value calculation as an additional source of variability in ambulatory blood pressure measurement. Am J Hypertens. 2010 Jul;23(7):725-31. doi: 10.1038/ajh.2010.47. Epub 2010 Mar 25.