Study of Renal Denervation in Patients With Heart Failure

NCT01954160 | Terminated Phase 2 Results DMC

• 2 other identifiers: Pro000470505U10HL084904
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 12

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Urine Sodium Excretion

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

  13 Weeks following Renal Denervation

Secondary Outcomes (26)

• Urine Volume

  13 Weeks following Renal Denervation

• 24-hour Urine Sodium Excretion

  13 Weeks following Renal Denervation

• Glomerular Filtration Rate

  13 Weeks following Renal Denervation

• Serum Cystatin C

  13 Weeks following Renal Denervation

• Blood Urea Nitrogen (BUN) Level

  13 Weeks following Renal Denervation

Study Arms (2)

Early Symplicity Renal Denervation

OTHER

Subjects undergo Symplicity Renal Denervation within 2 weeks of baseline visit will follow usual care after week 13 visit

Device: Symplicity Renal Denervation

Late Symplicity Renal Denervation

OTHER

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

Interventions

Symplicity Renal Denervation DEVICE

Renal denervation

Early Symplicity Renal Denervation; Late Symplicity Renal Denervation

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (12)

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02130, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02153, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Metro Health System

Cleveland, Ohio, 44115, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

The University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Kathy Moore
• Organization: Duke Clinical Research Institute

kathy.moore@dm.duke.edu

919-668-8065

Study Officials

• Adrian Hernandez, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Eugene Braunwald, MD

  Harvard University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: October 1, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 2, 2016
• Results First Posted: February 2, 2016

Record last verified: 2015-12

Locations

US (12)