Brief Title
Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
Official Title
Left Cardiac Sympathetic Denervation (LCSD) for Cardiomyopathy Feasibility Pilot Study
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.
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Feasibility
Secondary Outcome
Mortality and morbidity
Condition
Dilated Cardiomyopathy
Intervention
Left Cardiac Sympathetic Denervation (LCSD)
Study Arms / Comparison Groups
Left Cardiac Sympathetic Denervation (LCSD)
Description: Left Cardiac Sympathetic Denervation (LCSD) in addition to Optimal Medical Therapy (OMT)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
30
Start Date
November 24, 2016
Completion Date
February 2020
Primary Completion Date
November 2019
Eligibility 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, +27214046136, [email protected]
Location Countries
South Africa
Location Countries
South Africa
Administrative Informations
NCT ID
NCT03071653
Organization ID
001001001
Responsible Party
Principal Investigator
Study Sponsor
University of Cape Town
Collaborators
Medtronic
Study Sponsor
, ,
Verification Date
March 2017