PRESERVE: Study of Renal Denervation in Patients With Heart Failure

• Sponsor: Adrian Hernandez (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01954160
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Medtronic (Industry)
• Enrollment: 5
• Locations: 12
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Congestive heart failure is a common disorder in which the heart cannot pump enough blood to meet the needs of the rest of the body. Poor sodium handling by the kidneys is a damaging effect of heart failure, and it leads to symptoms of congestion such as shortness of breath or ankle swelling. Recent studies suggest that reducing the nerve activity to a kidney could reduce sodium retention and blood pressure. An improvement in the way the kidneys handle sodium may reduce disease progression and decrease symptoms for heart failure patients.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: Symplicity Renal Denervation	Phase 2

Detailed Description

Over the past decades, clinical trials in HF have been unable to alter the natural history of cardio-renal compromise. Fluid retention accounts for the majority of admissions for acute decompensated heart failure, and salt and water removal using intravenous (IV) diuretics has been the mainstay of therapy applied to this population.1 Over 20% of hospitalized patients in the Acute Decompensated Heart Failure National Registry (ADHERE) had serum creatinine values greater than 2.0 mg/dL2 with the majority of congested patients presenting with significantly elevated systolic blood pressures rather than low-output states.1 Administration of IV loop diuretics further produces intravascular volume depletion and reduction in glomerular filtration rates3 as well as an increase in neurohormonal activation.4 This is true regardless of whether LVEF is impaired or preserved.5 However, despite relieving symptoms, acute drug administrations (such as adenosine receptor antagonists or natriuretic peptide analogues) for short durations have not changed the long-term cardio-renal outcomes in large clinical trials.

Recent recognition of different phenotypes of cardio-renal syndrome has provided better characterization of patient populations to evaluate specific treatment approaches or interventions.6 There is now greater appreciation that patients with congestive HF depend not only on an adequate glomerular function for renal glomerular filtration, but also on adequate tubular function for effective sodium handling that may or may not be dependent on glomerular filtration.7 Despite optimizing intracardiac filling pressures, many patients with August 28, 2013 Page 10 of 58 cardio-renal compromise remain symptomatic, complaining of breathlessness and fatigue often associated with concomitant increase in neurohormonal up-regulation (e.g. natriuretic peptides) and poor outcomes.8 Since the majority of patients present with hypertension, it points to the possibility that congestive HF is precipitated by heightened sympathetic drive.

Animal models have demonstrated that both blood pressure control and renal tubular function/glomerular filtration (as a function of renal blood flow) can be directly influenced by renal sympathetic nerve activity,9-12 which has evolved to provide cardiovascular support in the setting of hypovolemia or profound cardiovascular collapse. Specifically, HF animal models with denervated kidneys have demonstrated improvement in renal blood flow and natriuresis (with restoration of Na+-K+ ATPase at the loop of Henle, as well as epithelial sodium pumps at the distal tubules). However, our understanding of how persistently activated renal sympathetic outflow can lead to exaggerated neurohormonal up-regulation and chemoreceptor regulation in humans is still evolving. As heightened cardio-renal compromise leads to disease progression and congestive HF, it is conceivable that an approach to selectively modulate renal sympathetic outflow may improve cardio-renal compromise as well as the target mechanism leading to symptomatic improvement in at-risk patients.

By establishing the mechanistic role of renal sympathetic outflow in patients with impaired sodium handling as a contributor to congestion in HF, we may better understand why patients with HF develop symptoms, retain salt and water, and activate neurohormonal systems. This trial will be hypothesis generating and will serve to inform a larger clinical trial in patients with congestion related to HF.

The Data Safety and Monitoring Board (DSMB), an independent committee assigned by the sponsor to oversee the conduct and safety of this study, met on May 12, 2014 to review information that had become available from another study of the renal artery denervation procedure using the same investigational catheter as the PRESERVE study. Even though there were no concerns for the safety of subjects that had the renal artery denervation, the DSMB decided to stop the PRESERVE study.

Based upon agreement with the FDA, the protocol was amended to reduce subject participation from 52 weeks to 13 weeks and to only collect limited safety information.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Promotion of Renal Sodium Excretion by Renal Sympathetic Denervation in Congestive Heart Failure
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: Early Symplicity Renal Denervation Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit	Device: Symplicity Renal Denervation; Renal denervation
Other: Late Symplicity Renal Denervation Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit	Device: Symplicity Renal Denervation; Renal denervation

Outcome Measures

Primary Outcome Measures

1. Urine Sodium Excretion [13 Weeks following Renal Denervation]

   Within-subject comparison of increase in urine sodium excretion following saline loading before RSD and 13 weeks following RSD.

Secondary Outcome Measures

1. Urine Volume [13 Weeks following Renal Denervation]

   Urine volume following furosemide therapy after sodium loading.

2. 24-hour Urine Sodium Excretion [13 Weeks following Renal Denervation]

   Difference in 24-hour urine sodium excretion, compared between pre-RSD and 13 weeks after RSD.

3. Glomerular Filtration Rate [13 Weeks following Renal Denervation]

   Estimated Glomerular Filtration Rate (GFR) by creatinine and cystatin C

4. Serum Cystatin C [13 Weeks following Renal Denervation]

   Study terminated early, endpoints not measured

5. Blood Urea Nitrogen (BUN) Level [13 Weeks following Renal Denervation]

   Study terminated early, endpoints not measured

6. Creatinine Clearance From 24-hour Urine Creatinine [13 Weeks following Renal Denervation]

   Study terminated early, endpoints not measured

7. Urine Albumin [13 Weeks following Renal Denervation]

   Urine albumin

8. Renal Resistive Index [13 Weeks following Renal Denervation]

   Intra-renal hemodynamics as measured by Renal Resistive Index (RRI) by renal Doppler ultrasonography Study terminated early, endpoints not measured

9. Left Ventricular End Systolic Volume [13 Weeks following Renal Denervation]

   Echo: Left ventricular end systolic volume Study terminated early, endpoints not measured

10. Left Ventricular Ejection Fraction [13 Weeks following Renal Denervation]

    Echo: Left Ventricular Ejection Fraction Study terminated early, endpoints not measured

11. Global Longitudinal Strain [13 Weeks following Renal Denervation]

    Echo: Global longitudinal strain Study terminated early, endpoints not measured

12. LV End Systolic Dimension (LVESd) [13 Weeks following Renal Denervation]

    Echo: LV end systolic dimension (LVESd)

13. LV End Diastolic Dimension (LVEDd) [13 Weeks following Renal Denervation]

    Echo: LV end diastolic dimension (LVEDd)

14. Left Atrial Size [13 Weeks following Renal Denervation]

    Echo: Left Atrial size

15. Plasma N-terminal Pro-brain Natriuretic Peptide [13 Weeks following Renal Denervation]

16. Resting Plasma Norepinephrine [13 Weeks following Renal Denervation]

17. Resting Urine Norepinephrine [13 Weeks following Renal Denervation]

18. Plasma Renin Activity [13 Weeks following Renal Denervation]

19. Plasma Aldosterone [13 Weeks following Renal Denervation]

20. 6 Minute Walk Test [13 Weeks following Renal Denervation]

21. Kansas City Cardiomyopathy Questionnaire Score [13 Weeks following Renal Denervation]

22. Patient Global Assessment [13 Weeks following Renal Denervation]

23. New York Heart Association (NYHA) Functional Classification [13 Weeks following Renal Denervation]

24. Heart Rate Variability [13 Weeks following Renal Denervation]

    Heart rate variability indices by Holter

25. Tissue Doppler Indices [13 Weeks following Renal Denervation]

    Echo: Tissue Doppler indices

26. Left Ventricular End Diastolic Volume [13 Weeks following Renal Denervation]

    Echo: Left Ventricular End Diastolic Volume

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, aged 21-80 years old.

• History of chronic HF (>6 months) with current NYHA II-III symptoms.

• Left Ventricular Ejection Fraction ≤40% on a clinically indicated echocardiogram obtained within 6 months prior to informed consent.

• Requires daily loop diuretic (≥40mg furosemide per day, or equivalent) to maintain euvolemia (absence of congestive signs including jugular venous distension with Jugular Venous Pressure > 7cm H20, ≥ moderate (2+) peripheral edema, S3).

• Optimized medical therapy for HF. Patients will be receiving guideline-recommended therapy (per the 2013 ACCF/AHA HF Guidelines) including angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker, beta-blockers, and aldosterone antagonists without changes in heart failure medication regimen (including diuretics) for previous 14 days.

• Systolic blood pressure (BP) ≥110 mmHg at time of informed consent.

• Able to maintain stable medications for 52 weeks.

• Suitable renal artery anatomy for Renal Sympathetic Denervation (RSD) procedure. All of the following criteria must be met, based on the screening renal Doppler ultrasound:

• ≥ 20mm treatable length in each renal artery,

• Diameter in treatable segments must be ≥4mm,

• Lone main renal vessel feeding each kidney.

Exclusion Criteria:

• Unable to comply with protocol or procedures.

• Evidence of orthostatic hypotension or known dysautonomia. Orthostatic hypotension is defined by ≥1 of the following feature(s) within 2-5 minutes of quiet standing:

• ≥ 20 mmHg fall in systolic pressure

• ≥ 10 mmHg fall in diastolic pressure

• Symptoms of cerebral hypoperfusion (e.g. dizziness or lightheadedness, visual blurring or darkening of the visual fields, syncope).

• Evidence of or history of renal artery stenosis, nephrectomy, or renal transplant.

• Significant renal impairment as defined by estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73m2 determined by Modification of Diet in Renal Disease (MDRD) equation.

• Significant proteinuria (>2g protein/daily protein excretion).

• Body mass index (BMI) >35 kg/m2.

• Acute coronary syndrome within last 4 weeks as defined by ECG changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or angina equivalent).

• Coronary revascularization procedures (percutaneous coronary intervention or cardiac artery bypass graft) and or valve surgery within 30 days of screening or expected procedures within the next 6 months.

• Cardiac resynchronization therapy, with or without implantable cardiac defibrillator within 90 days of screening or expected procedures within the next 6 months.

• Hypertrophic or restrictive cardiomyopathy, constrictive pericarditis, active myocarditis, active endocarditis, or complex congenital heart disease.

• Severe advanced HF, with ANY of the following features:

• Current or anticipated use of ventricular assist device within the next 6 months.

• Current or anticipated IV vasoactive drug therapy for HF management within the next 6 months.

• Listed cardiac transplant candidate, with transplantation likely within the next 6 months.

• Known allergic reactions to iodinated radiological contrast media or iodinated antiseptics.

• Greater than moderate mitral or aortic stenosis, and/or severe tricuspid regurgitation.

• Terminal illness (other than HF) with expected survival of less than 1 year.

• Female who is pregnant, nursing, or of childbearing potential not practicing effective birth control.

• Enrollment or planned enrollment in another clinical trial within the next 12 months.

• History of urinary outflow tract obstruction, bladder retention and/ or moderate to severe prostate hypertrophy.

• History of adrenal insufficiency

• History of untreated hypothyroidism

• Patients with non-cardiac dyspnea or fatigue due to frailty, motivational factors, pulmonary disease or orthopedic problems that precludes them from performing 6MWT (Six-Minute WalkTest).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30322
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02130
4	Tufts Medical Center	Boston	Massachusetts	United States	02153
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Washington University	St. Louis	Missouri	United States	63110
7	Duke University Medical Center	Durham	North Carolina	United States	27705
8	Metro Health System	Cleveland	Ohio	United States	44115
9	Cleveland Clinic	Cleveland	Ohio	United States	44195
10	University of Pennsylvania Health System	Philadelphia	Pennsylvania	United States	19104
11	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
12	The University of Vermont - Fletcher Allen Health Care	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• Adrian Hernandez
• National Heart, Lung, and Blood Institute (NHLBI)
• Medtronic

Investigators

• Principal Investigator: Adrian Hernandez, MD, Duke University
• Study Chair: Eugene Braunwald, MD, Harvard University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adrian Hernandez, Associate Professor, Duke University
• ClinicalTrials.gov Identifier: NCT01954160
• Other Study ID Numbers: Pro00047050; 5U10HL084904
• First Posted: Oct 1, 2013
• Last Update Posted: Feb 2, 2016
• Last Verified: Dec 1, 2015

• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Pre-assignment Detail	5 participants were enrolled. 4 subjects received treatment, 1 subject did not receive treatment due to ineligibility secondary to renal doppler findings.

Arm/Group Title	Early Renal Denervation	Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
Period Title: Overall Study
STARTED	5	0
COMPLETED	0	0
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	Early Renal Denervation	Late Renal Denervation	Total
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System	Total of all reporting groups
Overall Participants	4	0	4
Age (participants) [Number]
<=18 years	0 0%	0 NaN
Between 18 and 65 years	4 100%	4 Infinity
>=65 years	0 0%	0 NaN
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.5 (4.4)	52.5 (4.4)
Gender (participants) [Number]
Female	1 25%	1 Infinity
Male	3 75%	3 Infinity
Region of Enrollment (participants) [Number]
United States	4 100%	4 Infinity

Outcome Measures

1. Primary Outcome

Title	Urine Sodium Excretion
Description	Within-subject comparison of increase in urine sodium excretion following saline loading before RSD and 13 weeks following RSD.
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected, endpoints not measured

Arm/Group Title	Early Renal Denervation	Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
Measure Participants	0	0

2. Secondary Outcome

Title	Urine Volume
Description	Urine volume following furosemide therapy after sodium loading.
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

3. Secondary Outcome

Title	24-hour Urine Sodium Excretion
Description	Difference in 24-hour urine sodium excretion, compared between pre-RSD and 13 weeks after RSD.
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

4. Secondary Outcome

Title	Glomerular Filtration Rate
Description	Estimated Glomerular Filtration Rate (GFR) by creatinine and cystatin C
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

5. Secondary Outcome

Title	Serum Cystatin C
Description	Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

6. Secondary Outcome

Title	Blood Urea Nitrogen (BUN) Level
Description	Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

7. Secondary Outcome

Title	Creatinine Clearance From 24-hour Urine Creatinine
Description	Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

8. Secondary Outcome

Title	Urine Albumin
Description	Urine albumin
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

9. Secondary Outcome

Title	Renal Resistive Index
Description	Intra-renal hemodynamics as measured by Renal Resistive Index (RRI) by renal Doppler ultrasonography Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

10. Secondary Outcome

Title	Left Ventricular End Systolic Volume
Description	Echo: Left ventricular end systolic volume Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

11. Secondary Outcome

Title	Left Ventricular Ejection Fraction
Description	Echo: Left Ventricular Ejection Fraction Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

12. Secondary Outcome

Title	Global Longitudinal Strain
Description	Echo: Global longitudinal strain Study terminated early, endpoints not measured
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

13. Secondary Outcome

Title	LV End Systolic Dimension (LVESd)
Description	Echo: LV end systolic dimension (LVESd)
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

14. Secondary Outcome

Title	LV End Diastolic Dimension (LVEDd)
Description	Echo: LV end diastolic dimension (LVEDd)
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

15. Secondary Outcome

Title	Left Atrial Size
Description	Echo: Left Atrial size
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

16. Secondary Outcome

Title	Plasma N-terminal Pro-brain Natriuretic Peptide
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

17. Secondary Outcome

Title	Resting Plasma Norepinephrine
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

18. Secondary Outcome

Title	Resting Urine Norepinephrine
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

19. Secondary Outcome

Title	Plasma Renin Activity
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

20. Secondary Outcome

Title	Plasma Aldosterone
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

21. Secondary Outcome

Title	6 Minute Walk Test
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

22. Secondary Outcome

Title	Kansas City Cardiomyopathy Questionnaire Score
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

23. Secondary Outcome

Title	Patient Global Assessment
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Symplisity Renal Denervation	Late Symplisity Renal Denervation
Arm/Group Description	Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit Symplicity Renal Denervation: Renal denervation	Subjects following usual care until week 13 visit will then undergo Symplicity Renal Denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation: Renal denervation
Measure Participants	0	0

24. Secondary Outcome

Title	New York Heart Association (NYHA) Functional Classification
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Renal Denervation	Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
Measure Participants	0	0

25. Secondary Outcome

Title	Heart Rate Variability
Description	Heart rate variability indices by Holter
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Renal Denervation	Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
Measure Participants	0	0

26. Secondary Outcome

Title	Tissue Doppler Indices
Description	Echo: Tissue Doppler indices
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Renal Denervation	Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
Measure Participants	0	0

27. Secondary Outcome

Title	Left Ventricular End Diastolic Volume
Description	Echo: Left Ventricular End Diastolic Volume
Time Frame	13 Weeks following Renal Denervation

Outcome Measure Data

Analysis Population Description

Study terminated early, data not collected and therefore endpoints were not measured.

Arm/Group Title	Early Renal Denervation	Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System	Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
Measure Participants	0	0

Adverse Events

Time Frame	up to one year post randomization
Arm/Group Title	Early Renal Denervation		Late Renal Denervation
Arm/Group Description	Subjects undergo renal denervation within 2 weeks of baseline visit Symplicity Renal Denervation System		Subjects undergo renal denervation within 2 weeks of Week 13 visit Symplicity Renal Denervation System
All Cause Mortality
	Early Renal Denervation		Late Renal Denervation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Early Renal Denervation		Late Renal Denervation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/0 (NaN)
Cardiac disorders
Cardiomyopathy	1/4 (25%)	1	0/0 (NaN)	0
Metabolism and nutrition disorders
Hyperglycemia	1/4 (25%)	1	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Early Renal Denervation		Late Renal Denervation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/0 (NaN)
General disorders
Non Cardiac Chest Pain	1/4 (25%)	1	0/0 (NaN)	0
Musculoskeletal and connective tissue disorders
Groin Pain	1/4 (25%)	1	0/0 (NaN)	0

Limitations/Caveats

Data Safety Monitoring Board (DSMB) terminated trial based upon noted lack of efficacy in manufacturers pivotal trials. Endpoint data not collected or analyzed.

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.