PHARES Study: Management of Resistant Hypertension

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