Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction Clinical Trial

— UNLOAD-HFpEF  

Official title:

Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction - A Single Center Pilot Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05030987
• Other study ID #: UNLOAD-HFpEF
• Secondary ID: CIV-20-10-034846
• Status: Recruiting
• Phase: N/A
• Start date: November 30, 2021
• Est. completion date: March 31, 2026

Study information

• Verified date: April 2023
• Source: University of Leipzig
• Contact: Philipp Lurz, Prof. Dr.
• Phone: 49 341
• Email: philipp.lurz[@]medizin.uni-leipzig.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Heart failure with preserved ejection fraction has a high mortality, which is contrasted by a total absence of therapy options besides symptomatic diuretic treatment. This study aims to explore the potential of renal denervation as a treatment option for heart failure with preserved ejection fraction.

Description:

Heart failure is one of the most important diseases worldwide, with a 5-year mortality of up to 75% in symptomatic patients. While substantial progress has been made in the treatment of patients with reduced left ventricular ejection fraction (HFrEF), mortality for patients with heart failure and preserved ejection fraction (HFpEF) remains unchanged, despite a comparable prevalence and mortality of the disease as for heart failure with reduced ejection fraction.

HFpEF is a heterogeneous condition and has been a diagnostic and therapeutic challenge for clinicians and researchers over the past decades. While some rare cases of HFpEF can be attributed to specific diseases like amyloidosis, in most other patients common characteristics are increased ventricular filling pressures and ventricular and arterial stiffening as frequently caused by ageing, diabetes and arterial hypertension. Furthermore, increased sympathetic activity has been described as one pathogenic contributor to chronic heart failure and is associated with poor clinical prognosis. It also leads to a more pulsatile BP profile which can cause a mismatch in arterio-ventricular coupling.

The modulating effects on the sympathetic nervous system induced by renal denervation (RDN) should be beneficial in HFpEF, as they improve resting and exercise hemodynamics due to an improved ventriculoarterial coupling by reduced aortic stiffness and lower systemic blood pressure. In addition, RDN leads to optimized stroke volume and stroke work and might affect cardiac preload by improving blood distribution into the splanchnic compartment.

This study aims to explore the potential of RDN as a therapy for HFpEF in a single center pilot trial using a randomized, sham-controlled double-blind design.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. confirmed arterial hypertension (1-5 antihypertensive drugs without any dosage change in the preceding 4 weeks) and average systolic BP between >125 and =170 mmHg and diastolic BP =110 mmHg in 24h ambulatory blood pressure measurement (ABPM)

2. HFpEF (defined by clinical signs and/or symptoms of heart failure, objective structural cardiac abnormalities according to the ESC criteria [1], elevated NT-proBNP =125 pg/mL and left-ventricular ejection fraction =55%)

3. NYHA-Class II or III

4. Confirmation of an elevated cardiac filling pressures (either LVEDP >= 16 mmHg or PCWP >= 15 mmHg at rest or >=25 mmHg during exercise) by catheterization

5. Age 18-80 years

6. Written informed consent

Exclusion Criteria:

1. =1 main renal artery diameter <3.0 mm

2. main renal artery length < 20 mm

3. a single functioning kidney

4. presence of abnormal kidney tumors

5. renal artery aneurysm

6. pre-existing renal stent or history of renal artery angioplasty

7. fibromuscular disease of the renal arteries

8. presence of renal artery stenosis of any origin =50%

9. iliac/femoral artery stenosis precluding femoral access for RDN

10. fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects of the trial device on contraception).

11. participation in other interventional trials

12. patients under legal supervision or guardianship

13. suspected lack of compliance

14. pregnant women

15. Presence of intracardiac pacemakers or implantable cardioverter/defibrillators

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Hypertension
• Hypertension, Renal

Intervention

Procedure:
• Renal Denervation
Renal denervation in patients with HFpEF and uncontrolled hypertension
• Sham
Sham Treatment. After six months, cross-over is planned in all sham-treated patients and this patients will also receive a renal denervation.

Locations

Country	Name	City	State
Germany	Herzzentrum Leipzig, Universitätsklinik für Kardiologie	Leipzig

Sponsors (2)

Lead Sponsor	Collaborator
University of Leipzig	ReCor Medical, Inc.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	exercise PCPW at 20 W workload	To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment	6 months after randomization
Secondary	number of combination of death, increase in diuretic therapy, hospitalization for heart failure, worsening NYHA-class, change in pulmonary pressure parameters	number of combined endpoint in RDN and SHAM patients	6, 12 and 24 months after RDN
Secondary	Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements	difference between RDN and sham	6 months after randomization
Secondary	Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements	Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements, compared to baseline values	6, 12 and 24 months after RDN
Secondary	Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability	difference between RDN and sham	6 months after randomization
Secondary	Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability	Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability, compared to baseline values	6, 12 and 24 months after RDN
Secondary	Difference in ventriculo-arterial coupling	Difference in ventriculo-arterial coupling (by end-systolic elastance and arterial elastance) as acquired by invasive measurement	6 months after randomization
Secondary	Change in CMR-based hemodynamics	Change in CMR-based hemodynamics (difference between RDN and sham) as compared to baseline values	6 months after randomization
Secondary	Change in ventriculo-arterial coupling	Change in ventriculo-arterial coupling (cMRI and echocardiogram) (difference between RDN and sham) as compared to baseline values	6 months after randomization
Secondary	Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload)	Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload) (difference between RDN and sham) as compared to baseline values	6 months after randomization
Secondary	Difference in peak PCWP	Difference in peak PCWP (difference between RDN and sham) as compared to baseline values	6 months after randomization
Secondary	Difference in NT-proBNP	Difference in NT-proBNP (difference between RDN and sham) as compared to baseline	6 months after randomization
Secondary	Difference in NT-proBNP	Difference in NT-proBNP as compared to baseline	6, 12 and 24 months after RDN
Secondary	number of patients with Hospitalizations for heart failure	number of patients with Hospitalizations for heart failure (difference between RDN and sham)	6 months after randomization
Secondary	difference in All-cause Mortality	All-cause Mortality (difference between RDN and sham)	6 months after randomization
Secondary	difference in cardiac mortality	cardiac mortality (difference between RDN and sham)	6 months after randomization
Secondary	difference in major adverse cardiovascular events	major adverse cardiovascular events (composite of cardiac death, myocardial infarction, stroke and hospitalization for heart failure) (difference between RDN and sham)	6 months after randomization
Secondary	difference in number of Adverse Events	Adverse events (difference between RDN and sham)	6 months after randomization
Secondary	difference in Frequency of patients with controlled hypertension	Frequency of patients with controlled hypertension (blood pressure within treatment goals in ABPM as recommended by the European Society of Cardiology) (difference between RDN and sham)	6 months after randomization
Secondary	difference in Frequency of patients with controlled hypertension	Frequency of patients with controlled hypertension (blood pressure within treatment goals in ABPM as recommended by the European Society of Cardiology) as compared to baseline	6, 12 and 24 months after RDN
Secondary	Difference in 6-minute walk distance	Difference in 6-minute walk distance (difference between RDN and sham)	6 months after randomization
Secondary	Difference in 6-minute walk distance	Difference in 6-minute walk distance as compared to baseline	6, 12 and 24 months after RDN
Secondary	Change in exercise BP and maximum maximum exercise capacity	Change in exercise BP between baseline and 6 months and maximum exercise capacity between baseline and 6 months (difference between RDN and sham)	6 months after randomization
Secondary	Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)	Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)	6 months after randomization
Secondary	Change in Minnesota living with heart failure questionnaire	Change in Minnesota living with heart failure questionnaire, compared to baseline	6, 12 and 24 months after RDN