Clinical trial NCT05030987: Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction
Official title: Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction - A Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction
Hypertension, Renal
Keywords: Renal Denervation
Hypertension
Heart Failure with Preserved Ejection Fraction
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: ReCor Medical, Inc.
First posted: 2021-09-01
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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 (European Society of Cardiology) 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

Primary outcomes:
measure: exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload
timeFrame: 6 months after randomization
Secondary outcomes:
measure: number of combination of death, increase in diuretic therapy, hospitalization for heart failure, worsening NYHA-class, change in pulmonary pressure parameters
timeFrame: 6, 12 and 24 months after RDN
measure: Change in mean Pulmonary artery (PA) pressure, estimated pulmonary artery diastolic pressure (ePAD) and PA pressure variability from pulmonary pressure sensor measurements
timeFrame: 6 months after randomization
measure: Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements
timeFrame: 6, 12 and 24 months after RDN
measure: Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
timeFrame: 6 months after randomization
measure: Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
timeFrame: 6, 12 and 24 months after RDN
measure: Difference in ventriculo-arterial coupling
timeFrame: 6 months after randomization
measure: Change in Cardiac magnetic resonance (CMR) based hemodynamics
timeFrame: 6 months after randomization
measure: Change in ventriculo-arterial coupling
timeFrame: 6 months after randomization
measure: Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload)
timeFrame: 6 months after randomization
measure: Difference in peak PCWP
timeFrame: 6 months after randomization
measure: Difference in NT-proBNP
timeFrame: 6 months after randomization
measure: Difference in NT-proBNP
timeFrame: 6, 12 and 24 months after RDN
measure: number of patients with Hospitalizations for heart failure
timeFrame: 6 months after randomization
measure: difference in All-cause Mortality
timeFrame: 6 months after randomization
measure: difference in cardiac mortality
timeFrame: 6 months after randomization
measure: difference in major adverse cardiovascular events
timeFrame: 6 months after randomization
measure: difference in number of Adverse Events
timeFrame: 6 months after randomization
measure: difference in Frequency of patients with controlled hypertension
timeFrame: 6 months after randomization
measure: difference in Frequency of patients with controlled hypertension
timeFrame: 6, 12 and 24 months after RDN
measure: Difference in 6-minute walk distance
timeFrame: 6 months after randomization
measure: Difference in 6-minute walk distance
timeFrame: 6, 12 and 24 months after RDN
measure: Change in exercise BP and maximum maximum exercise capacity
timeFrame: 6 months after randomization
measure: Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)
timeFrame: 6 months after randomization
measure: Change in Minnesota living with heart failure questionnaire
timeFrame: 6, 12 and 24 months after RDN
Other outcomes:
Locations:
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin III
state: Sachsen Anhalt
city: Berlin
country: Germany
facility: BG Klinikum Unfallkrankenhaus Berlin gGmbH
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik und Poliklinik für Kardiologie
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig, Universitätsklinik für Kardiologie
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg Universität Mainz, Zentrum für Kardiologie / Kardiologie 1
Study officials:
affiliation: Herzzentrum Leipzig, Universitätsklinik für Kardiologie
name: Karl Fengler, PhD
role: STUDY_CHAIR
References: