Clinical trial NCT02539810: Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)
Official title: Optimum and Stepped Care Standardised Antihypertensive Treatment With or Without Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis. ANDORRA TRIAL
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
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
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2015-09-03
Enrollment: 4
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Inclusion criteria for the renal angiogram procedure:

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

Inclusion criteria for the randomization:

* 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

Primary outcomes:
measure: Mean change in diurnal systolic blood pressure assessed by ambulatory BP monitoring (ABPM)
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Adverse events of renal artery stenting
timeFrame: Baseline to 12 months
measure: Change in average 24-hour and nighttime Systolic Blood Pressure by ABPM
timeFrame: Baseline to 12 months
measure: Change in average 24-hour, daytime and nighttime diastolic Blood Pressure by ABPM
timeFrame: Baseline to 12 months
measure: Change in Systolic/diastolic Blood Pressure by home blood pressure monitoring
timeFrame: Baseline to 12 months
measure: Change in office Systolic/diastolic Blood Pressure
timeFrame: Baseline to 12 months
measure: Antihypertensive medication score
timeFrame: Baseline to 12 months
measure: Detection of the drugs in urine by LC-MS/MS
timeFrame: Baseline to 12 months
measure: Renal artery restenosis in patients of the stenting group assessed by duplex ultrasound and/or renal CTA
timeFrame: Baseline to 12 months
measure: Adverse cardiovascular (CV) events
timeFrame: Baseline to 12 months
measure: Change in plasma creatinine and eGFR
timeFrame: Baseline to 12 months
measure: Clinical renal events: renal death, progressive renal insufficiency (i.e. need for dialysis), need for permanent renal replacement therapy, need of target vessel stenting in the SOMT group (number of crossovers)
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Nice
country: France
facility: Hopital Pasteur
state: Alpes-Maritimes
city: Bordeaux
country: France
facility: Hopital Saint Andre - CHU Bordeaux
state: Gironde
city: Toulouse
country: France
facility: Hopital Rangueil - CHU Toulouse
state: Haute-Garonne
city: Montpellier
country: France
facility: Hopital Lapeyronie - CHU Montpellier
state: Herault
city: Dinard
country: France
facility: Hopital Arthur Gardiner
state: Ille-et-Vilaine
city: Rennes
country: France
facility: Hopital Pontchaillou - CHU Rennes
state: Ille-et-Vilaine
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste
state: Isere
city: La Tronche
country: France
facility: Hopital Michallon - CHU Grenoble
state: Isere
city: Vandoeuvre les Nancy
country: France
facility: Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu
state: Meurthe-et-Moselle
city: Vandoeuvre les Nancy
country: France
facility: Hopital de Brabois
state: Meurthe-et-Moselle
city: Lille
country: France
facility: Hopital Cardiologique - CHRU Lille
state: Nord
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
state: Puy-de-Dome
city: Lyon
country: France
facility: Hopital de la Croix-Rousse - CHU Lyon
state: Rhone
city: Paris
country: France
facility: Hopital de la Pitie Salpetriere
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou (HEGP)
Study officials:
affiliation: HEGP - APHP
name: Michel AZIZI
role: PRINCIPAL_INVESTIGATOR
References: