Study of Renal Denervation in Patients With Heart Failure (PRESERVE)

This study is currently recruiting participants.
Verified January 2014 by Duke University
Sponsor:
Collaborators:
Medtronic
Information provided by (Responsible Party):
Adrian Hernandez, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01954160
First received: September 24, 2013
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Heart Failure
Device: Symplicity Renal Denervation System
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Promotion of Renal Sodium Excretion by Renal Sympathetic Denervation in Congestive Heart Failure

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Urine Sodium Excretion [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Within-subject comparison of increase in urine sodium excretion following saline loading before RSD and 13 weeks following RSD.


Secondary Outcome Measures:
  • Urine volume [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Urine volume following furosemide therapy after sodium loading.

  • 24-hour urine sodium excretion [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Difference in 24-hour urine sodium excretion, compared between pre-RSD and 13 weeks after RSD.

  • Glomerular Filtration Rate [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Estimated GFR by creatinine and cystatin C

  • Serum cystatin C [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • BUN level [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Creatinine clearance from 24-hour urine creatinine [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Urine albumin [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Urine albumin

  • Renal Resistive Index [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: Yes ]
    Intra-renal hemodynamics as measured by Renal Resistive Index (RRI) by renal Doppler ultrasonography

  • Left ventricular end systolic volume [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: Left ventricular end systolic volume

  • Left Ventricular Ejection Fraction [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: Left Ventricular Ejection Fraction

  • Global longitudinal strain [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: Global longitudinal strain

  • LV end systolic dimension (LVESd) [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: LV end systolic dimension (LVESd)

  • LV end diastolic dimension (LVEDd) [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: LV end diastolic dimension (LVEDd)

  • Left Atrial size [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: Left Atrial size

  • Plasma N-terminal pro-brain natriuretic peptide [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Resting plasma norepinephrine [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Resting urine norepinephrine [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Plasma renin activity [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Plasma aldosterone [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • 6 Minute Walk Test [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Kansas City Cardiomyopathy Questionnaire Score [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Patient Global Assessment [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • NYHA Functional Classification [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
  • Heart Rate Variability [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Heart rate variability indices by Holter

  • Tissue Doppler indices [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: Tissue Doppler indices

  • Left Ventricular End Diastolic Volume [ Time Frame: 13 Weeks following Renal Denervation ] [ Designated as safety issue: No ]
    Echo: Left Ventricular End Diastolic Volume


Estimated Enrollment: 64
Study Start Date: December 2013
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Early Renal Denervation
Subjects undergo renal denervation within 2 weeks of baseline visit
Device: Symplicity Renal Denervation System
Late Renal Denervation
Subjects undergo renal denervation within 2 weeks of Week 13 visit
Device: Symplicity Renal Denervation System

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, aged 21-80 years old.
  • History of chronic HF (>6 months) with current NYHA II-III symptoms.
  • LVEF ≤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 JVP > 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 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 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01954160

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States
Contact: Gail Snell       gail.snell@emoryhealthcare.org   
Principal Investigator: Javed Butler, MD         
United States, Massachusetts
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States
Contact: Susan Anello       manello@partners.org   
Principal Investigator: Michael Givertz, MD         
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States
Contact: Diane Cocca-Spofford       dcoccaspofford@partners.org   
Principal Investigator: Marc Semigran, MD         
Tufts Medical Center Not yet recruiting
Boston, Massachusetts, United States
Contact: Gail Jamieson       gjamieson@tuftsmedicalcenter.org   
Principal Investigator: Gordon Huggins, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States
Contact: Janet Gatzke       gatzke.janet@mayo.edu   
Principal Investigator: Margaret Redfield, MD         
United States, Missouri
Washington University Not yet recruiting
St. Louis, Missouri, United States
Contact: Jean Flanagan       jflanaga@dom.wustl.edu   
Principal Investigator: Douglas Mann, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States
Contact: Patricia Adams       patricia.adams@dm.duke.edu   
Principal Investigator: Michael Felker, MD         
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States
Contact: Teresa Fonk       fonkt@ccf.org   
Principal Investigator: Wilson Tang, MD         
Sub-Investigator: Randall Starling, MD         
Metro Health System Not yet recruiting
Cleveland, Ohio, United States
Contact: Mary Dettmer       mdettmer@metrohealth.org   
Principal Investigator: Mark Dunlap, MD         
United States, Pennsylvania
University of Pennsylvania Health System Not yet recruiting
Philadelphia, Pennsylvania, United States
Contact: Marisa Konig       marisa.konig@uphs.upenn.edu   
Principal Investigator: Kenneth Margulies, MD         
Thomas Jefferson University Hospital Not yet recruiting
Philadelphia, Pennsylvania, United States
Contact: Barbara Gallagher       barbara.gallagher@jefferson.edu   
Principal Investigator: David Whellan, MD         
United States, Vermont
The University of Vermont - Fletcher Allen Health Care Not yet recruiting
Burlington, Vermont, United States
Contact: Michaelanne Rowen       michaelanne.rowen@vtmednet.org   
Principal Investigator: Martin LeWinter, MD         
Sponsors and Collaborators
Adrian Hernandez
Medtronic
Investigators
Principal Investigator: Adrian Hernandez, MD Duke University
Study Chair: Eugene Braunwald, MD Harvard University
  More Information

No publications provided

Responsible Party: Adrian Hernandez, Associate Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01954160     History of Changes
Other Study ID Numbers: Pro00047050, 5U10HL084904
Study First Received: September 24, 2013
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 23, 2014