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

Primary Purpose

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

Status
Terminated
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Renal artery Angioplasty plus stenting.
Anti hypertensive, statin and antiplatelet medication.
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Pasteur
  • Hopital Saint Andre - CHU Bordeaux
  • Hopital Rangueil - CHU Toulouse
  • Hopital Lapeyronie - CHU Montpellier
  • Hopital Arthur Gardiner
  • Hopital Pontchaillou - CHU Rennes
  • Groupe Hospitalier Mutualiste
  • Hopital Michallon - CHU Grenoble
  • Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu
  • Hopital de Brabois
  • Hopital Cardiologique - CHRU Lille
  • CHU Clermont-Ferrand
  • Hopital de la Croix-Rousse - CHU Lyon
  • Hopital de la Pitie Salpetriere
  • Hopital Europeen Georges Pompidou (HEGP)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Renal artery stenting

standardized and optimized medication regimen

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Mean change in diurnal systolic blood pressure assessed by ambulatory BP monitoring (ABPM)

Secondary Outcome Measures

Adverse events of renal artery stenting
Change in average 24-hour and nighttime Systolic Blood Pressure by ABPM
Change in average 24-hour, daytime and nighttime diastolic Blood Pressure by ABPM
Change in Systolic/diastolic Blood Pressure by home blood pressure monitoring
Change in office Systolic/diastolic Blood Pressure
Antihypertensive medication score
Detection of the drugs in urine by LC-MS/MS
Renal artery restenosis in patients of the stenting group assessed by duplex ultrasound and/or renal CTA
Adverse cardiovascular (CV) events
Change in plasma creatinine and eGFR
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)

Full Information

First Posted
July 28, 2015
Last Updated
January 24, 2018
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France
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1. Study Identification

Unique Protocol Identification Number
NCT02539810
Brief Title
Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)
Acronym
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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Study Start Date
September 2015 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
July 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Renal artery stenting
Arm Type
Experimental
Arm Description
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.
Arm Title
standardized and optimized medication regimen
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Renal artery Angioplasty plus stenting.
Other Intervention Name(s)
RA Stent
Intervention Description
renal artery stenting
Intervention Type
Drug
Intervention Name(s)
Anti hypertensive, statin and antiplatelet medication.
Other Intervention Name(s)
SOMT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mean change in diurnal systolic blood pressure assessed by ambulatory BP monitoring (ABPM)
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Adverse events of renal artery stenting
Time Frame
Baseline to 12 months
Title
Change in average 24-hour and nighttime Systolic Blood Pressure by ABPM
Time Frame
Baseline to 12 months
Title
Change in average 24-hour, daytime and nighttime diastolic Blood Pressure by ABPM
Time Frame
Baseline to 12 months
Title
Change in Systolic/diastolic Blood Pressure by home blood pressure monitoring
Time Frame
Baseline to 12 months
Title
Change in office Systolic/diastolic Blood Pressure
Time Frame
Baseline to 12 months
Title
Antihypertensive medication score
Time Frame
Baseline to 12 months
Title
Detection of the drugs in urine by LC-MS/MS
Time Frame
Baseline to 12 months
Title
Renal artery restenosis in patients of the stenting group assessed by duplex ultrasound and/or renal CTA
Time Frame
Baseline to 12 months
Title
Adverse cardiovascular (CV) events
Time Frame
Baseline to 12 months
Title
Change in plasma creatinine and eGFR
Time Frame
Baseline to 12 months
Title
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)
Time Frame
Baseline to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel AZIZI
Organizational Affiliation
HEGP - APHP
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Pasteur
City
Nice
State/Province
Alpes-Maritimes
ZIP/Postal Code
06002
Country
France
Facility Name
Hopital Saint Andre - CHU Bordeaux
City
Bordeaux
State/Province
Gironde
ZIP/Postal Code
33075
Country
France
Facility Name
Hopital Rangueil - CHU Toulouse
City
Toulouse
State/Province
Haute-Garonne
ZIP/Postal Code
31059
Country
France
Facility Name
Hopital Lapeyronie - CHU Montpellier
City
Montpellier
State/Province
Herault
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Arthur Gardiner
City
Dinard
State/Province
Ille-et-Vilaine
ZIP/Postal Code
35800
Country
France
Facility Name
Hopital Pontchaillou - CHU Rennes
City
Rennes
State/Province
Ille-et-Vilaine
ZIP/Postal Code
35033
Country
France
Facility Name
Groupe Hospitalier Mutualiste
City
Grenoble
State/Province
Isere
ZIP/Postal Code
38028
Country
France
Facility Name
Hopital Michallon - CHU Grenoble
City
La Tronche
State/Province
Isere
ZIP/Postal Code
38700
Country
France
Facility Name
Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu
City
Vandoeuvre les Nancy
State/Province
Meurthe-et-Moselle
ZIP/Postal Code
54500
Country
France
Facility Name
Hopital de Brabois
City
Vandoeuvre les Nancy
State/Province
Meurthe-et-Moselle
ZIP/Postal Code
54511
Country
France
Facility Name
Hopital Cardiologique - CHRU Lille
City
Lille
State/Province
Nord
ZIP/Postal Code
59037
Country
France
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
State/Province
Puy-de-Dome
ZIP/Postal Code
63000
Country
France
Facility Name
Hopital de la Croix-Rousse - CHU Lyon
City
Lyon
State/Province
Rhone
ZIP/Postal Code
69004
Country
France
Facility Name
Hopital de la Pitie Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hopital Europeen Georges Pompidou (HEGP)
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

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

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