Renal Artery Denervation in Chronic Heart Failure (REACH-Pilot)

Renal Artery Denervation in Chronic Heart Failure- Pilot

Heart failure is a common condition with debilitating symptoms and a poor prognosis. Patients with heart failure have a massively overactive sympathetic nervous system which attempts to compensate for their poorly functioning heart. This ultimately has only detrimental effects.

One of the principle mediators for this sympathetic response is found in the nerve cells in the kidneys. Whilst a significant proportion of medications used to treat heart failure act on these harmful pathways, none target the kidney sympathetic-nerve cells specifically. Additionally, because of their multiple sites of action these drugs all have side effects.

A new procedure that has recently been developed for the treatment of high blood pressure is renal denervation. This involves inserting a small catheter through the femoral artery and passing it to the kidney artery under x-ray guidance. From there, using radiofrequency waves, the sympathetic nerves within the kidney can be destroyed.

The investigators anticipate that this procedure will have a significant positive effect on patients with heart failure and aim to perform a pilot safety study on 7 individuals with advanced heart failure to assess its safety and effectiveness. The investigators hypothesise that renal artery denervation will lead to significant clinical and biochemical improvements in patients with marked heart failure.

Study Overview

• Status: Completed
• Conditions: Congestive Cardiac Failure
• Intervention / Treatment: Procedure: Renal Artery Denervation

Detailed Description

One of the key physiological changes seen in heart failure patients is overactivity of the sympathetic nervous system. This is a homeostatic response produced by the body in an attempt to compensate for a poorly functioning heart and the resultant underperfused tissues. In acute heart failure this has a positive effect but in chronic heart failure, the long standing sympathetic overactivity causes multiple undesirable side effects including profound vasoconstriction, increased sodium reabsorption by the kidneys, renin release and decreased renal blood flow. Afferent and efferent sympathetic chains in the renal artery play an important role in the mediation of this response.

Current management of heart failure principally hinges on drugs that attempt to attenuate or interrupt this response via renin angiotensin system, adrenoreceptors or the renal tubules. These drugs have multiple side effects, partly because of their multiple sites of action. None directly target the sympathetic discharge at its source.

The development of renal artery denervation opens a unique opportunity for potentially longlasting relief of this intense renal sympathetic over-activity. The technique has a current role in the management of resistant hypertension where it has shown very favourable results with minimal side effects. The investigators envisage that this technique could also be highly beneficial to patients with heart failure by directly interrupting this sympathetic overactivity. This initial study involving 7 patients is a pilot safety study to assess this potential.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W21NY
    • St Mary's Hospital
  • London, United Kingdom, W120HS
    • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• congestive cardiac failure
• maximal medical therapy
• NYHA class III/IV

Exclusion Criteria:

• clinically unstable
• pre-existing renal disease
• unfavourable anatomy
• tortuous femoral anatomy
• unable to consent
• CRT present or eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Renal Artery Denervation; Ontervention	Procedure: Renal Artery Denervation; Radiofrequency ablation of the renal artery sympathetic outflow tract.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	To ensure that patients with heart failure are able to acceptably tolerate the procedure and its potential effect on haemodynamics.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA classification	To assess NYHA classification of dyspnoea	1 year
6 minute walk test	To assess impact on 6 minute walk test	1 year
Cardiopulmonary testing	To assess the impact on cardiopulmonary exercise testing	1 year
NT-proBNP	To assess the impact on NT-proBNP levels	1 year
Urinary excretion of renal hormones	To assess the impact on the urinary excretion of renal hormones	1 year

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Justin E Davies, PhD, Imperial College London

Publications and helpful links

General Publications

• Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009 Apr 11;373(9671):1275-81. doi: 10.1016/S0140-6736(09)60566-3. Epub 2009 Mar 28.
• Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J, Hamady M, Hughes AD, Sever PS, Sobotka PA, Francis DP. First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study. Int J Cardiol. 2013 Jan 20;162(3):189-92. doi: 10.1016/j.ijcard.2012.09.019. Epub 2012 Sep 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 29, 2011
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (Estimate): April 25, 2012

Study Record Updates

• Last Update Posted (Estimate): August 23, 2016
• Last Update Submitted That Met QC Criteria: August 22, 2016
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: NYHA class III or IV; Maximal medical therapy; Not eligible for CRT
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: JROSM0135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: waiting