Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)

NCT ID: NCT02539810

Last Updated: 2018-01-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-07-31

Brief Summary

The ANDORRA study is a, multicenter, prospective, open, randomized, controlled blinded endpoint trial (PROBE) comparing two treatment strategies (renal artery stenting + standardized and optimized medical treatment [SOMT] versus SOMT alone) of 12 months duration in patients with confirmed resistant hypertension (RH) and angiographically proven grade III unilateral or bilateral atherosclerotic renal artery stenosis (ARAS) ≥ 60%.

Detailed Description

All eligible patients diagnosed with RH on office BP measurements and unilateral or bilateral ARAS ≥60% on a non-invasive test (CT-angiogram or MR-angiogram) will receive a standardized optimized triple antihypertensive treatment for 4 weeks. After 4 weeks, patients with confirmed RH by ABPM (daytime ABPM ≥ 135 or 85 mmHg) and no clinically significant increase in plasma creatinine from baseline (< 30%) will undergo a renal angiogram to confirm the degree of ARAS ≥60% in diameter.

Immediately after the renal angiography, all patients will undergo flow fractional reserve (FFR) measurements. Once FFR measurements have been done and all criteria are met, patients will be randomized in the angiography room to either renal artery stenting + SOMT (stenting group) versus SOMT (control group) whatever the results of the FFR in a 1:1 ratio. Both groups will continue the SOMT during follow-up.

The SOMT will be prescribed from the inclusion visit until the 6 month-visit after randomization. After randomization, the antihypertensive treatment will be adapted according to the results of home BP (HBP) at monthly visits starting 2 months after randomization. After the 6-month visit, the antihypertensive treatment adaptation will be left at the discretion of the physician in charge of the patient.

Conditions

Hypertension; Hypertension Resistant to Conventional Therapy; Angiographically Proven Grade III Unilateral or Bilateral Atherosclerotic Renal Artery Stenosis (ARAS) Greater Than or Equal to 60 Percent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Renal artery stenting

Renal artery angioplasty plus stenting and standardized and optimized medication regimen.

Patients are treated with renal artery stenting plus a standardized optimal medical treatment, including the antihypertensive treatment which is adapted every month starting two month after randomization on the basis of home BP monitoring results at follow-up visits.

Group Type: EXPERIMENTAL

Renal artery Angioplasty plus stenting.

Intervention Type: DEVICE

renal artery stenting

Anti hypertensive, statin and antiplatelet medication.

Intervention Type: DRUG

Slow release indapamide 1.5 mg/d (or furosemide 40 mg/d if eGFR is \< 30 mL/min/1.73m²) + irbesartan 300 mg/d + amlodipine 10 mg/d + aspirin 75 mg/d (or clopidogrel 75 mg/d in case of allergy or gastrointestinal intolerance to aspirin) + atorvastatin 20 mg/d. After randomization, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d and spironolactone 12.5 to 25 mg/d, will be sequentially added from months two to five in both groups if home blood pressure remains more than or equal to 135/85 mm Hg.

standardized and optimized medication regimen

Patients are treated with a standardized optimal medical treatment including the antihypertensive treatment which is adapted every month starting two month after randomization on the basis of home BP monitoring results at follow-up visits.

Group Type: ACTIVE_COMPARATOR

Anti hypertensive, statin and antiplatelet medication.

Intervention Type: DRUG

Slow release indapamide 1.5 mg/d (or furosemide 40 mg/d if eGFR is \< 30 mL/min/1.73m²) + irbesartan 300 mg/d + amlodipine 10 mg/d + aspirin 75 mg/d (or clopidogrel 75 mg/d in case of allergy or gastrointestinal intolerance to aspirin) + atorvastatin 20 mg/d. After randomization, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d and spironolactone 12.5 to 25 mg/d, will be sequentially added from months two to five in both groups if home blood pressure remains more than or equal to 135/85 mm Hg.

Interventions

Renal artery Angioplasty plus stenting.

renal artery stenting

Intervention Type: DEVICE

Anti hypertensive, statin and antiplatelet medication.

Slow release indapamide 1.5 mg/d (or furosemide 40 mg/d if eGFR is \< 30 mL/min/1.73m²) + irbesartan 300 mg/d + amlodipine 10 mg/d + aspirin 75 mg/d (or clopidogrel 75 mg/d in case of allergy or gastrointestinal intolerance to aspirin) + atorvastatin 20 mg/d. After randomization, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d and spironolactone 12.5 to 25 mg/d, will be sequentially added from months two to five in both groups if home blood pressure remains more than or equal to 135/85 mm Hg.

Intervention Type: DRUG

Other Intervention Names

RA Stent; SOMT

Eligibility Criteria

Inclusion Criteria

• Age: 40 to 80 Years
• Men or women
• Supine office BP ≥ 140 and/or 90 mmHg at screening despite a stable medication regimen including full tolerated doses of 3 or more anti-hypertensive treatments of different classes, including a diuretic.
• Unilateral or bilateral ARAS of a main renal artery ≥60% diagnosed by renal CT- angiogram (or MR-angiogram if there is a contraindication to perform CT) performed in the year before
• One or two functional kidney(s) ≥ 70 mm in pole-to-pole length
• eGFR ≥ 20 ml/min/1.73 m² (MDRD formula)
• Signed informed consent
• Social insurance coverage

• RH confirmed by daytime ABPM ≥ 135 or 85 mmHg after 1 month treatment with SOMT at Visit V1.

• Unilateral or bilateral ARAS of a main renal artery ≥ 60% confirmed on renal angiogram by Quantitative Vascular Analysis (QVA)
• Increase in plasma creatinine < 30% after 4-week SOMT

Exclusion Criteria

• Fibromuscular dysplasia of renal artery or other non-atherosclerotic renal artery stenosis
• Other secondary form of hypertension excluded on the basis of a clinical, hormonological and/or imaging work-up
• Restenosis after a previous renal angioplasty or stenting
• Only a stenosis of an accessory renal artery supplying <1/2 of the ipsilateral renal parenchyma
• Additional indication of ARAS stenting (Malignant hypertension, ≥ 30% increase in plasma creatinine after renin angiotensin system (RAS) blocker or after RAS blocker and diuretic administration, flash pulmonary edema)
• Kidney pole-to-pole length < 70 mm
• Vascular disease precluding access for stenting
• Abrupt vessel closure or dissection after diagnostic angiography
• Contraindication to renal artery stenting according the notice for use of the stents
• eGFR < 20 ml/min/1.73 m² (MDRD)
• History of transient ischemic accident (TIA) or cerebrovascular accident (CVA) during the 3 months prior to visit 1
• History of acute heart failure or heart failure (NYHA class III-IV) within the 3 months prior to visit 1
• History of myocardial infarction, unstable angina, coronary bypass or percutaneous coronary angioplasty during the 3 months prior to visit 1
• Abdominal aortic aneurysm with indication for surgery or EVAR (Endovascular Aneurysm Repair)
• Known history of cholesterol embolism
• Brachial circumference of ≥ 42 cm
• Severe contrast media allergy, not amenable to pre-treatment
• Allergy to aspirin or clopidogrel
• Atrial fibrillation
• Comorbid condition causing life expectancy ≤ 3 years
• Unlikely to co-operate in the study and/or poor compliance anticipated by the investigator
• Participant not affiliated to the French social security
• Pregnancy or breastfeeding
• Guardianship for incapacity

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel AZIZI

Role: PRINCIPAL_INVESTIGATOR

HEGP - APHP

Locations

Hopital Pasteur

Nice, Alpes-Maritimes, France

Hopital Saint Andre - CHU Bordeaux

Bordeaux, Gironde, France

Hopital Rangueil - CHU Toulouse

Toulouse, Haute-Garonne, France

Hopital Lapeyronie - CHU Montpellier

Montpellier, Herault, France

Hopital Arthur Gardiner

Dinard, Ille-et-Vilaine, France

Hopital Pontchaillou - CHU Rennes

Rennes, Ille-et-Vilaine, France

Groupe Hospitalier Mutualiste

Grenoble, Isere, France

Hopital Michallon - CHU Grenoble

La Tronche, Isere, France

Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Hopital de Brabois

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Hopital Cardiologique - CHRU Lille

Lille, Nord, France

CHU Clermont-Ferrand

Clermont-Ferrand, Puy-de-Dome, France

Hopital de la Croix-Rousse - CHU Lyon

Lyon, Rhone, France

Hopital de la Pitie Salpetriere

Paris, , France

Hopital Europeen Georges Pompidou (HEGP)

Paris, , France

Countries

France

Other Identifiers

P140914

Identifier Type: OTHER

Identifier Source: secondary_id

P140914

Identifier Type: -

Identifier Source: org_study_id