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

• ClinicalTrials.gov Identifier: NCT03071653
• Recruitment Status: Unknown
• First Posted: March 7, 2017
• Last Update Posted: March 7, 2017
• 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

Detailed Description:

STUDY SUMMARY

TITLE Left Cardiac Sympathetic Denervation (LCSD) for Cardiomyopathy Study DESIGN Phase II feasibility parallel randomised controlled trial (RCT) AIMS Assess the feasibility and safety of LCSD in patients with cardiomyopathy and heart failure OUTCOME MEASURES Recruitment rates, retention, follow-up and safety POPULATION 30 patients with heart failure secondary to cardiomyopathy ELIGIBILITY Adult participants with ischemic and non-ischemic cardiomyopathy DURATION 18 months follow up

METHODS:

Participants will be randomized to receive LCSD in addition to optimal medical therapy in the intervention arm (15 patients) and optimal medical therapy in the active control arm (15 patients). Participants would be recruited from both inpatient and outpatient general medical and cardiology wards and clinics at Groote Schuur Hospital where patients with the syndrome of heart failure are frequently referred for subspecialty evaluation and management. Eligible patients who meet the inclusion criteria would be randomized to undergo LCSD in addition to optimal medical therapy (intervention arm) or receive standard optimal medical therapy (active placebo). Optimal therapy for patients with cardiomyopathy and heart failure currently consists of an ace-inhibitor or angiotensinogen receptor blocker, beta-blocker, mineralocorticoid receptor antagonist with or without a loop diuretic, and digoxin. All patients in the study would receive an implantable loop recorder to allow for the accurate determination of episodes of symptomatic and asymptomatic ventricular tachyarrhythmias. In order not to lose all of the clinical outcome information obtained in the pilot phase of the study, we would propose only assessing the pre-specified feasibility and safety aspects of the study and keeping the data on efficacy outcomes blinded for inclusion in the fully powered main study.

The LCSD procedure 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 (3). LCSD raises the ventricular fibrillation threshold without impairing cardiac contractility or reducing heart rate. LCSD results in pre-ganglionic denervation, thus preventing re-innervation and producing permanent antifibrillatory effects. This procedure can be performed by video-assisted thoracoscopic surgery (VATS) usually in less than 45 minutes and will be conducted by thoracic surgeons at Groote Schuur Hospital. The lead thoracic surgeon (J.R.) has a large experience in performing this procedure for the indication of hyperhidrosis in over 200 patients (personal communication). This experienced thoracic surgeon will lead a team of thoracic surgeons (T.P., L.M.) to perform the procedure.

Implantable loop recorder (ILR) insertion The implantable loop recorder is a small device that will be inserted at the end of the LCSD procedure by the thoracic surgeon or after enrolment in the optimal medical therapy arm by a cardiologist. This loop recorder is inserted under sterile conditions in the catheter laboratory or operating theatre. In the catheter laboratory, the device is inserted under local anaesthetic, subcutaneously over the left precordium and usually takes less than 15 minutes. The implantable loop recorder is a well-established device to quantify and detect atrial and ventricular tachyarrhythmias with an excellent safety record. The device has a battery life of up to 3 years and can be removed via a small skin incision at the end of the study. Implantable loop recorder insertion does not carry risk of known major complications. There is a minimal risk (<1%) of complications (infection, bleeding) as the device is implanted subcutaneously. Potential complications include superficial skin infections that readily responds to antibiotics. Device removal is easy to perform and is seldom required.

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:

1. A renin angiotensin system blocker at highest tolerated doses (e.g., enalapril 10mg twice daily or equivalent)
2. A mineralocorticoid receptor antagonist (e.g., Spironolactone 25-50mg daily or equivalent)
3. A Beta-blocker (e.g., Carvedilol 25mg twice daily or equivalent)
4. The use of a loop diuretic and digitalis will be clinically driven and used at the discretion of the attending clinician

Study Design

• 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

• 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

Contact: Constance Philander; +27214046136; connie.talliard@uct.ac.za

Contact: Noloyiso Mtana; +27214046086; nolly.mtana@uct.ac.za

Locations

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

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

• 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:

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