AzTrials
AzTrials

HypertensionPhase 4NCT00224549

PHARES Study: Management of Resistant Hypertension

A Phase 4 study testing irbesartan, amlodipine and hydrochlorothiazide in people with Hypertension, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hypertension
What is being tested?
irbesartan, amlodipine and hydrochlorothiazide
How many people
180 participants
Where
1 siteFrance
Study dates
Apr 2005to Aug 2009
Phase
Phase 4
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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Investigation Clinical Center European Georges Pompidou Hospital

    Paris, Île-de-France Region, 75015

Other trials in France

About this study

Official title: Management of Resistant Hypertension -Pharmacokinetic Assessment of Different Antihypertensive Regimen -Comparison of Two Treatment Strategies: Increase Sodium Depletion or Combined Blockage of Renin-angiotensin System (RAS)

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.

Read the detailed description

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
Hypertension
Being tested
irbesartan, amlodipine and hydrochlorothiazide
Keywords
Resistant hypertension, Combined diuretic therapy, Combined RAS blockers
Medical subject headings
Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • irbesartan, amlodipine and hydrochlorothiazideDrug

    irbesartan, amlodipine and hydrochlorothiazide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean day-time systolic blood pressure (SBP) at week 12, measured with an average blood pressure measurement (ABPM) device

    Mean day-time systolic blood pressure (SBP) at week 12, measured with an average blood pressure measurement (ABPM) device

    Measured: at week 12

Secondary outcomes (11)

  1. Efficacy: mean day-time diastolic blood pressure (DBP) at week 12, mean 24 hours SBP and DBP at week 12 measured with an ABPM device

    hours SBP and DBP at week 12 measured with an ABPM device

    Measured: at week 12,

  2. Safety and tolerability:

    Safety and tolerability:

    Measured: during the study

  3. During the study BP will be evaluated every 4 weeks by home blood pressure measurement [HBPM] in order to detect hypotension)

    During the study BP will be evaluated every 4 weeks by home blood pressure measurement [HBPM] in order to detect hypotension)

    Measured: every 4 weeks

  4. Biological examinations:

    Biological examinations:

    Measured: during the study

  5. blood and urinary electrolytes with creatinemia at week 0, 4, 8, 10 and 12

    blood and urinary electrolytes with creatinemia at week 0, 4, 8, 10 and 12

    Measured: at week 0, 4, 8, 10 and 12

  6. brain natriuretic peptide (BNP), active renin, aldosterone at week 0 and 12

    brain natriuretic peptide (BNP), active renin, aldosterone at week 0 and 12

    Measured: at week 0 and 12

  7. Other explorations:

    Other explorations:

    Measured: during

  8. Treatment compliance (study drug accounting, N-acetyl-seryl-aspartyl-lysyl-proline [Ac SDKP] for angiotensin converting enzyme inhibitor [ACEi])

    Treatment compliance (study drug accounting, N-acetyl-seryl-aspartyl-lysyl-proline [Ac SDKP] for angiotensin converting enzyme inhibitor [ACEi])

    Measured: during the study

  9. Echocardiography (week 0 and 12)

    Echocardiography (week 0 and 12)

    Measured: week 0 and 12

  10. Endothelial function (week 0 and 12)

    Endothelial function (week 0 and 12)

    Measured: week 0 and 12

  11. Pharmacokinetics of drugs (week 0 and 12)

    Pharmacokinetics of drugs (week 0 and 12)

    Measured: week 0 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2005 (estimated)
  2. Study startApr 2005
  3. Primary completionAug 2009
  4. Study completionAug 2009

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00224549
Sponsor's protocol ID
P040407
Status last verified
Mar 2007
First submitted
16 Sep 2005
Last updated
28 Feb 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27755389

  • 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.

    PubMed 20339354

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing irbesartan, amlodipine and hydrochlorothiazide in people with Hypertension, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

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 2 inclusion and 8 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 28 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Mean day-time systolic blood pressure (SBP) at week 12, measured with an average blood pressure measurement (ABPM) device (time frame: at week 12). 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 NCT00224549, which also lists 2 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 28 Feb 2011.

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