Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study

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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