REDUCE-HTN: Treatment of Resistant Hypertension Using a Radiofrequency Percutaneous Transluminal Angioplasty Catheter

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01541865
• Collaborator: (none)
• Enrollment: 146
• Locations: 26
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The Study objective is to assess the performance of the Vessix V2 Renal Denervation System for the treatment of uncontrolled hypertension using an innovative percutaneous Radio Frequency (RF) balloon catheter renal denervation device.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Device: Renal Denervation	N/A

Detailed Description

This study will evaluate the hypothesis that the Vessix V2 Renal Denervation System can be employed to reduce systolic and diastolic blood pressure at 6 months as compared to pre-treatment baseline blood pressures.

Patient blood pressure will be measured by in the office according to recognized international techniques and standards.

Procedural success shall be defined as ability to complete the renal denervation treatment using the V2 balloon catheter device and RF generator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Resistant Hypertension Using a Radiofrequency Percutaneous Transluminal Angioplasty Catheter (REDUCE-HTN) - POST MARKET APPROVAL CLINICAL SURVEILLANCE STUDY
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: Renal Denvervation All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.	Device: Renal Denervation; percutaneous renal denervation using the Vessix RF balloon catheter; Other Names: Vessix V2 Renal Denervation System

Outcome Measures

Primary Outcome Measures

1. Change in Systolic and Diastolic Blood Pressure at Six (6) Months as Measured by Office-based Blood Pressure Assessment [Baseline and 6 months]

   Change in systolic and diastolic blood pressure at six (6) months as measured by office-based blood pressure assessment following therapeutic renal denervation compared to baseline. Office blood pressure will be measured using a validated electronic device according to a standardized procedure. .

2. Change in Systolic and Diastolic Blood Pressure at Six (6) Months as Measured by 24-hour Ambulatory Blood Pressure [Baseline and 6 months]

   Change in systolic and diastolic blood pressure at six (6) months as measured by 24-hour ambulatory blood pressure monitoring (ABPM) following therapeutic renal denervation compared to baseline using a validated ABPM device.

Secondary Outcome Measures

1. Absence of Flow Limiting Stenosis in the Renal Artery [6 months]

   Absence of flow limiting stenosis in the renal artery at six (6) months follow up time point as measured by renal duplex ultrasound

2. Renal Artery Dissection or Perforation During the Procedure That Requires Stenting or Surgery [Duration of the procedure (average of 65 minutes)]

3. Renal Artery Infarction or Embolus [Duration of the procedure (average of 65 minutes)]

4. Cerebrovascular Accident (CVA) at Time of Procedure [Duration of the procedure (average of 65 minutes)]

5. Myocardial Infarction at Time of Procedure [Duration of the procedure (average of 65 minutes)]

6. Sudden Cardiac Death at Time of Procedure [Duration of the procedure (average of 65 minutes)]

7. Angiographically-documented Renal Stenosis Requiring an Intervention [2 Years]

8. Chronic Symptomatic Orthostatic Hypotension [2 Years]

9. Hypertensive Emergency Necessitating Hospital Admission (Unrelated to Medication and/or Non-compliance) [2 Years]

10. Reduction in Estimated Glomerular Filtration Rate (eGFR) >25% [2 Years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects who have provided written informed consent;

2. Subjects who are ≥ 18 years and ≤ 75 years of age;

3. Subjects who have Systolic Blood Pressure (SBP) ≥ 160 mm Hg based on an average of three (3) office-based blood pressure readings (seated) measured according to protocol;

4. Subjects with ≥ 3 anti-hypertensive drugs at maximally tolerated doses with stable regimen for at least 2 weeks prior to enrollment

5. Subjects with a estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m^2;

6. Suitable renal artery anatomy

7. Subjects who are willing and able to comply with all study procedures.

Exclusion Criteria:

1. Subjects with known/diagnosed secondary hypertension;

2. Subjects who are contraindicated for anticoagulation medications (heparin, aspirin, Angiomax, etc.), analgesic medications (morphine, fentanyl, etc.), anxiolytic medications (alprazolam, lorazepam, diazepam, etc.) or other medications required for an interventional procedure;

3. Subjects with known bleeding or hyper-coagulation disorders;

4. Subjects who have type 1 diabetes mellitus;

5. Subjects who have experienced a myocardial infarction, unstable angina pectoris, uncompensated heart failure, or a cerebrovascular accident within six (6) months prior to the screening visit, or have widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques;

6. Subjects who have planned percutaneous vascular or surgical intervention for any reason within the next 6 months;

7. Subjects who have hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous;

8. Subjects who have an implantable cardioverter defibrillator, pacemaker, or clinically significant abnormal electrocardiogram

9. Subjects who have any serious medical condition, which in the opinion of the investigator, may adversely affect patient safety or the efficacy of the procedure in the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia);

10. Subjects who are pregnant, nursing or planning to become pregnant;

11. Subjects who have a known, unresolved history of drug use or alcohol abuse/dependency;

12. Subjects who are currently enrolled in any investigational study wherein patient participation has not been completed;

13. Subjects who, for any reason, may not be able to understand or comply with instructions;

14. Subjects who are contraindicated for intravascular contrast material;

15. Subjects who are currently taking estrogen or any estrogen-like compound.

16. Subjects who have had a prior renal denervation procedure

17. Subjects with prior intervention to right or left renal artery;

18. Subjects with ≥ 30% renal artery stenosis

19. Subjects with severe femoral, renal, iliac or aortic calcification that may cause a potential complication at the time of the procedure;

20. Subjects in which the physician is unable to safely cannulate the renal artery;

21. Subjects in which the physician is unable to percutaneously access the femoral artery;

22. Subjects with one kidney.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Vincent's Hospital	Sydney	New South Wales	Australia	2010
2	The Prince Charles Hospital, Cardiology Clinical Research Centre	Brisbane	Queensland	Australia	4032
3	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
4	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
5	Monash Cardiovascular Research Centre (Monash Heart)	Clayton	Victoria	Australia	3168
6	AKH Linz	Linz		Austria	4020
7	Salzburger Landeskliniken Universitats Krankenhaus	Salzburg		Austria	A-5020
8	OLV Ziekenhuis	Aalst		Belgium
9	Cliniques Universiaires Saint-Luc	Brussels		Belgium
10	Hôpital Européen Georges Pompidou	Paris		France
11	Clinic Pasteur	Toulouse		France	F-31076
12	Zentralklinik Bad Berka GmbH	Bad Berka		Germany	99437
13	Kardiologische Praxis Main-Taunus	Bad Soden/Taunus		Germany	65812
14	Vascular Center Berlin, Ev. Königin Elisabeth Hospital	Berlin		Germany	10365
15	St. Vincenz Krankenhaus Abt. Kardiologie	Essen		Germany	45141
16	CardioVascular Center, Sankt Katharinen Krakenhaus	Frankfurt		Germany	60389
17	Hamburg University Cardiovascular Center	Hamburg		Germany	22527
18	Saarland University Hospital Department of Internal Medicine III Non-surgical Intensive Care, Cardiology and Angiology	Homburg/Saar		Germany	D-66421
19	University Leipzig	Leipzig		Germany	04109
20	German Heart Center Munich	Münich		Germany	80636
21	Academic Medical Center	Amsterdam		Netherlands	1105AZ
22	Erasmus Medical Center-Thorax Center	Rotterdam		Netherlands	3015CE
23	Auckland City Hospital	Grafton	Auckland	New Zealand	1023
24	Mercy Angiography Unit Ltd	Auckland		New Zealand	1023
25	University Hospital of Geneva, Cardiology Center	Geneva		Switzerland	1211
26	Switzerland University Hospital Clinic for Cardiology	Zürich		Switzerland	8091

Sponsors and Collaborators

• Boston Scientific Corporation

Investigators

• Principal Investigator: Horst Sievert, M.D., CardioVascular Center Frankfurt, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT01541865
• Other Study ID Numbers: CR002-020
• First Posted: Mar 1, 2012
• Last Update Posted: Nov 25, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Boston Scientific Corporation: hypertension, renal denervation, uncontrolled hypertension, medication resistant hypertension
• Additional relevant MeSH terms: Hypertension

Study Results

Participant Flow

Recruitment Details	Enrollment of up to 150 subjects was planned; 146 subjects were enrolled at 23 centers in the Europe, Australia and New Zealand from February 22, 2012 to April 8, 2013.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Period Title: Overall Study
STARTED	146
COMPLETED	124
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Overall Participants	146
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (10.4)
Sex: Female, Male (Count of Participants)
Female	57 39%
Male	89 61%
Race/Ethnicity, Customized (participants) [Number]
White	135 92.5%
Black, Asian, Other	11 7.5%
Region of Enrollment (participants) [Number]
New Zealand	21 14.4%
Austria	13 8.9%
Netherlands	5 3.4%
Belgium	17 11.6%
Australia	31 21.2%
France	8 5.5%
Switzerland	2 1.4%
Germany	49 33.6%
Type 2 Diabetes (participants) [Number]
Type 2 Diabetes	41 28.1%
Non-Diabetic	105 71.9%
Coronary Artery Disease (participants) [Number]
Coronary Artery Disease	55 37.7%
No Coronary Artery Disease	91 62.3%
Congestive Heart Failure (participants) [Number]
Congestive Heart Failure	3 2.1%
No Congestive Heart Failure	143 97.9%
Dyslipidemia (participants) [Number]
Dyslipidemia	85 58.2%
No Dyslipidemia	61 41.8%
Baseline Systolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	182.4 (18.4)
Baseline Diastolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	100.2 (14.0)
Heart Rate (beats/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/min]	71.7 (14.8)
Estimated glomerular filtration rate (eGFR) (mL/min/1.73m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73m^2]	82.7 (22.5)
Serum Creatinine (micromol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micromol/L]	82.0 (20.0)
Number of Antihypertensive Medications per Patient (Antihypertensive Medications per Patient) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Antihypertensive Medications per Patient]	4.8 (1.5)
Antihypertensive Medications (participants) [Number]
Subjects on greater than or equal to 5 medications	79 54.1%
Subjects on 4 medications	38 26%
Subjects on 3 medications	26 17.8%
Subjects on 2 medications	3 2.1%

Outcome Measures

1. Primary Outcome

Title	Change in Systolic and Diastolic Blood Pressure at Six (6) Months as Measured by Office-based Blood Pressure Assessment
Description	Change in systolic and diastolic blood pressure at six (6) months as measured by office-based blood pressure assessment following therapeutic renal denervation compared to baseline. Office blood pressure will be measured using a validated electronic device according to a standardized procedure. .
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 3 participants were not evaluable.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	143
Systolic	-24.5 (22.1)
Diastolic	-10.3 (12.7)

2. Secondary Outcome

Title	Absence of Flow Limiting Stenosis in the Renal Artery
Description	Absence of flow limiting stenosis in the renal artery at six (6) months follow up time point as measured by renal duplex ultrasound
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 3 participants were not evaluable.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	143
Number [participants w/o flow limiting stenosis]	139 95.2%

3. Primary Outcome

Title	Change in Systolic and Diastolic Blood Pressure at Six (6) Months as Measured by 24-hour Ambulatory Blood Pressure
Description	Change in systolic and diastolic blood pressure at six (6) months as measured by 24-hour ambulatory blood pressure monitoring (ABPM) following therapeutic renal denervation compared to baseline using a validated ABPM device.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 76 participants were not evaluable at either the baseline or 6 month assessment.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	70
Systolic	-8.0 (14.6)
Diastolic	-5.7 (9.2)

4. Secondary Outcome

Title	Renal Artery Dissection or Perforation During the Procedure That Requires Stenting or Surgery
Time Frame	Duration of the procedure (average of 65 minutes)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	146
Number [participants]	0 0%

5. Secondary Outcome

Title	Renal Artery Infarction or Embolus
Time Frame	Duration of the procedure (average of 65 minutes)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	146
Number [participants]	0 0%

6. Secondary Outcome

Title	Cerebrovascular Accident (CVA) at Time of Procedure
Time Frame	Duration of the procedure (average of 65 minutes)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	146
Number [participants]	0 0%

7. Secondary Outcome

Title	Myocardial Infarction at Time of Procedure
Time Frame	Duration of the procedure (average of 65 minutes)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	146
Number [participants]	0 0%

8. Secondary Outcome

Title	Sudden Cardiac Death at Time of Procedure
Time Frame	Duration of the procedure (average of 65 minutes)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	146
Number [participants]	0 0%

9. Secondary Outcome

Title	Angiographically-documented Renal Stenosis Requiring an Intervention
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 22 participants were not evaluable.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	124
Number [participants]	1 0.7%

10. Secondary Outcome

Title	Chronic Symptomatic Orthostatic Hypotension
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 22 participants were not evaluable.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	124
Number [participants]	0 0%

11. Secondary Outcome

Title	Hypertensive Emergency Necessitating Hospital Admission (Unrelated to Medication and/or Non-compliance)
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 22 participants were not evaluable.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	124
Number [participants]	10 6.8%

12. Secondary Outcome

Title	Reduction in Estimated Glomerular Filtration Rate (eGFR) >25%
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat; all participants in the study were to undergo clinical follow up to provide the information needed for this endpoint; 25 participants were not evaluable.

Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
Measure Participants	121
Number [participants]	16 11%

Adverse Events

Time Frame	Adverse events were collect through the 2 year follow up visit.
Arm/Group Title	Renal Denervation
Arm/Group Description	All subjects who meet the inclusion criteria and are enrolled in this trial will be treated with the Vessix Renal Denervation System.
All Cause Mortality
	Renal Denervation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Renal Denervation
	Affected / at Risk (%)	# Events
Total	69/146 (47.3%)
Cardiac disorders
Myocardial Infarction	4/146 (2.7%)	6
Congestive Heart Failure	5/146 (3.4%)	8
Other Cardiac - Chest Pain/Angina	7/146 (4.8%)	8
Other Cardiac - Fibrillation	5/146 (3.4%)	5
Other Cardiac - Tachycardia	1/146 (0.7%)	1
Gastrointestinal disorders
Other - Gastrointestinal/Rectal	6/146 (4.1%)	7
General disorders
Other Neurological	2/146 (1.4%)	2
Other - Thoracic/Abdominal Pain	4/146 (2.7%)	4
Other - Hernia	1/146 (0.7%)	1
Other - Deconditioning post medical illness	1/146 (0.7%)	1
Other - Dementia	1/146 (0.7%)	1
Other - Nausea	1/146 (0.7%)	1
Other - Overdose	1/146 (0.7%)	1
Infections and infestations
Other Infectious/Inflammatory	9/146 (6.2%)	10
Other - Inflammation/Infection	10/146 (6.8%)	14
Metabolism and nutrition disorders
Other - Diabetes	5/146 (3.4%)	6
Musculoskeletal and connective tissue disorders
Other - Skeletal/Connective Tissue	13/146 (8.9%)	19
Psychiatric disorders
Other - Suicide Ideation	1/146 (0.7%)	1
Renal and urinary disorders
Renal Insufficiency	1/146 (0.7%)	1
Renal Failure	3/146 (2.1%)	3
Other - Hypertension	13/146 (8.9%)	21
Reproductive system and breast disorders
Unanticipated Adverse Events - Prolapsis Uteri	1/146 (0.7%)	1
Other - Priapismus	1/146 (0.7%)	1
Other - Prostate Carcinoma	1/146 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/146 (0.7%)	1
Other Pulmonary	7/146 (4.8%)	7
Other - Sleep Apnoea	1/146 (0.7%)	1
Surgical and medical procedures
Access Site Infection	2/146 (1.4%)	2
Clot or Thrombus Formation	1/146 (0.7%)	1
Hematoma	1/146 (0.7%)	1
Other Vascular - Stenosis	1/146 (0.7%)	1
Pseudoaneurysm	1/146 (0.7%)	1
Other - Flank Pain	1/146 (0.7%)	1
Other - Digestive (vomiting)	1/146 (0.7%)	1
Other - Hypertensive Crisis	4/146 (2.7%)	5
Other Cardiac - Hypertensive episode	1/146 (0.7%)	2
Acute Occlusion/Vessel Closure	1/146 (0.7%)	1
Stent Required	1/146 (0.7%)	1
Other - Elective Surgery	2/146 (1.4%)	2
Vascular disorders
Other Vascular - Carotid Stenosis	1/146 (0.7%)	1
Other Renal - Renal Calcification	1/146 (0.7%)	1
Stroke	2/146 (1.4%)	2
Other - Limb oedema/ Ulceration	2/146 (1.4%)	2
Other - Coronary Sub-Occlusion	1/146 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Renal Denervation
	Affected / at Risk (%)	# Events
Total	70/146 (47.9%)
General disorders
Pain	23/146 (15.8%)	23
Anaesthesia Related - Nausea/Vomiting	12/146 (8.2%)	14
Dizziness	16/146 (11%)	18
Hypertension	14/146 (9.6%)	14
Renal and urinary disorders
Reduced Kidney Function	9/146 (6.2%)	9
Skin and subcutaneous tissue disorders
Access Site Complications	20/146 (13.7%)	22
Hematoma	18/146 (12.3%)	19

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.