Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study (LCSD)

• Sponsor: University of Cape Town
• Collaborator: Medtronic
• Information provided by (Responsible Party): Mpiko Ntsekhe, University of Cape Town

Study Description

Brief Summary:

A randomized controlled trial to test the potential safety and efficacy of LCSD in patients with heart failure due to non-ischemic and ischemic cardiomyopathy at the University of Cape Town. Left Cardiac Sympathetic Denervation (LCSD) is a surgical intervention that modulates the autonomic innervation of the cardiac system. This is important because: a] sympathetic and parasympathetic tone has a profound effect on the threshold for ventricular tachyarrhythmias-the main cause of sudden cardiac death in this population; and b] autonomic dysfunction (which is characterized by an imbalance between sympathetic and parasympathetic activation), plays an important detrimental role in the pathophysiology and progression of heart failure.

Condition or disease	Intervention/treatment	Phase
Dilated Cardiomyopathy; Ischemic Cardiomyopathy; Non-ischemic Cardiomyopathy	Procedure: Left Cardiac Sympathetic Denervation (LCSD); Other: Optimal Medical Therapy	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Randomised Control Trial
Masking:	None (Open Label)
Primary Purpose:	Other
Official Title:	Left Cardiac Sympathetic Denervation (LCSD) for Cardiomyopathy Feasibility Pilot Study
Actual Study Start Date :	November 24, 2016
Estimated Primary Completion Date :	November 2019
Estimated Study Completion Date :	February 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Left Cardiac Sympathetic Denervation (LCSD); Left Cardiac Sympathetic Denervation (LCSD) in addition to Optimal Medical Therapy (OMT)	Procedure: Left Cardiac Sympathetic Denervation (LCSD); The procedure involves the surgical removal of the lower half of the left stellate ganglion (T1) and thoracic ganglia (T2-T4), thereby removing the pro-arrhythmic noradrenergic input to the ventricles; Other: Optimal Medical Therapy; All eligible patients with heart failure and depressed left ventricular systolic function will receive guideline and evidence based optimal tolerated medical therapy. The level of risk associated with optimal medical therapy is considered very low. For the majority of patients with heart failure and depressed left ventricular systolic function this will include: A renin angiotensin system blocker at highest tolerated doses (e.g., enalapril 10mg twice daily or equivalent); A mineralocorticoid receptor antagonist (e.g., Spironolactone 25-50mg daily or equivalent); A Beta-blocker (e.g., Carvedilol 25mg twice daily or equivalent); The use of a loop diuretic and digitalis will be clinically driven and used at the discretion of the attending clinician
OMT only; Optimal Medical Therapy (OMT) only	Other: Optimal Medical Therapy; All eligible patients with heart failure and depressed left ventricular systolic function will receive guideline and evidence based optimal tolerated medical therapy. The level of risk associated with optimal medical therapy is considered very low. For the majority of patients with heart failure and depressed left ventricular systolic function this will include: A renin angiotensin system blocker at highest tolerated doses (e.g., enalapril 10mg twice daily or equivalent); A mineralocorticoid receptor antagonist (e.g., Spironolactone 25-50mg daily or equivalent); A Beta-blocker (e.g., Carvedilol 25mg twice daily or equivalent); The use of a loop diuretic and digitalis will be clinically driven and used at the discretion of the attending clinician

Outcome Measures

Primary Outcome Measures :

1. Feasibility [ Time Frame: 36 months ]
   Recruitment rate
2. Feasibility [ Time Frame: 36 months ]
   Patient retention
3. Procedure related complications [ Time Frame: 36 months ]
   Measured by:• Horner's syndrome in those under going LCSD • Pneumothorax in those undergoing LCSD • Implantable loop recorder site sepsis

Secondary Outcome Measures :

1. Mortality and morbidity [ Time Frame: 36 months ]
   Measured by: All cause mortality; Heart failure related mortality; Hospital admissions; Ventricular arrhythmias;
2. Functional capacity: Measured by 6 minute walk test Quality of life at 6 months Admission to hospital for heart failure Functional Capacity [ Time Frame: 6 monthly for 36 months ]
   Measured by 6 minute walk test
3. Functional capacity: Quality of life (EQ-5D questionnaire) Quality of life at 6 months Admission to hospital for heart failure Functional Capacity [ Time Frame: 6 monthly for 36 months ]
   Quality of life (EQ-5D questionnaire)
4. End Systolic and Diastolic volumes [ Time Frame: 6 monthly for 36 months ]
   End Systolic and Diastolic volumes as determined by Echocardiography

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• At least 18 years of age
• New York Heart Association (NYHA) II/III stable heart failure due to an ischemic or non-ischemic cardiomyopathy with a Left Ventricular Ejection Fraction <=35% based on Echocardiogram, ERNA or MRI performed in the last 12 months. For the purpose of this study, Ischemic cardiomyopathy will be defined as Left Ventricular systolic dysfunction (Ejection Fraction <35%) associated with 75% narrowing of at least 1 of the 3 major coronary arteries, a documented history of a ST elevation myocardial infarction or significant regional wall motion abnormality on an echocardiogram. Non-ischemic cardiomyopathy will be defined as Left Ventricular systolic dysfunction <35% in the absence of known coronary artery disease or regional wall motion abnormality on echocardiography.
• No history of a prior cardiac arrest or sustained (>30 seconds or <30s if haemodynamically unstable) ventricular tachyarrhythmia.
• Signed informed consent forms will be available in IsiXhosa, Afrikaans and English.

Exclusion Criteria:

• History of prior unexplained syncope, sudden cardiac arrest or ventricular arrhythmia
• Peripartum cardiomyopathy or cardiomyopathy associated with thyrotoxicosis
• History of coronary revascularization or percutaneous intervention in the preceding 3 months
• Myocardial infarction in the preceding 1 month
• NYHA IV at enrollment
• Patient taking an antiarrhythmic drug (not including beta-blockers)
• Pregnancy
• Any non-cardiac condition that is associated with a high likelihood of death during the trial such as major organ dysfunction or malignancy.

Contacts and Locations

Contacts

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Contact: Constance Philander	+27214046136	connie.talliard@uct.ac.za
Contact: Noloyiso Mtana	+27214046086	nolly.mtana@uct.ac.za

Locations

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South Africa
University of Cape Town	Recruiting
Cape Town, Western Cape, South Africa, 7925
Contact: Constance Philander +27214046136 connie.talliard@uct.ac.za
Contact: Noloyiso Mtana +27214046086 nolly.mtana@uct.ac.za
Principal Investigator: Mpiko Ntsekhe
Principal Investigator: Ashley Chin
Sub-Investigator: Charle Viljoen
Sub-Investigator: Peter Schwartz
Sub-Investigator: Jacques Roussouw
Sub-Investigator: Tim Pennel
Sub-Investigator: Jacques Sherman

Sponsors and Collaborators

University of Cape Town

Medtronic

More Information

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Responsible Party:	Mpiko Ntsekhe, Professor, University of Cape Town
ClinicalTrials.gov Identifier:	NCT03071653 History of Changes
Other Study ID Numbers:	001001001
First Posted:	March 7, 2017
Last Update Posted:	March 7, 2017
Last Verified:	March 2017

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Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Mpiko Ntsekhe, University of Cape Town:

Cardiomyopathy; Left Cardiac Sympathetic Denervation

Additional relevant MeSH terms:

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Cardiomyopathies; Cardiomyopathy, Dilated; Heart Diseases; Cardiovascular Diseases; Cardiomegaly