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Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction (UNLOAD-HFpEF)

Primary Purpose

Heart Failure With Preserved Ejection Fraction, Hypertension, Renal

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Renal Denervation
Sham
Sponsored by
University of Leipzig
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction focused on measuring Renal Denervation, Hypertension, Heart Failure with Preserved Ejection Fraction

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. confirmed arterial hypertension (1-3 antihypertensive drugs without any dosage change in the preceding 4 weeks) and average systolic/diastolic BP between >130/70 and ≤170/110 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 (LVEDP >= 16 mmHg and 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

Sites / Locations

  • Herzzentrum Leipzig, Universitätsklinik für KardiologieRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

RDN

Sham

Arm Description

Renal Denervation

Sham Procedure

Outcomes

Primary Outcome Measures

exercise PCPW at 20 W workload
To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment

Secondary Outcome Measures

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
Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements
difference between RDN and sham
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
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
difference between RDN and sham
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
Difference in ventriculo-arterial coupling
Difference in ventriculo-arterial coupling (by end-systolic elastance and arterial elastance) as acquired by invasive measurement
Change in CMR-based hemodynamics
Change in CMR-based hemodynamics (difference between RDN and sham) as compared to baseline values
Change in ventriculo-arterial coupling
Change in ventriculo-arterial coupling (cMRI and echocardiogram) (difference between RDN and sham) as compared to baseline values
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
Difference in peak PCWP
Difference in peak PCWP (difference between RDN and sham) as compared to baseline values
Difference in NT-proBNP
Difference in NT-proBNP (difference between RDN and sham) as compared to baseline
Difference in NT-proBNP
Difference in NT-proBNP as compared to baseline
number of patients with Hospitalizations for heart failure
number of patients with Hospitalizations for heart failure (difference between RDN and sham)
difference in All-cause Mortality
All-cause Mortality (difference between RDN and sham)
difference in cardiac mortality
cardiac mortality (difference between RDN and sham)
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)
difference in number of Adverse Events
Adverse events (difference between RDN and sham)
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)
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
Difference in 6-minute walk distance
Difference in 6-minute walk distance (difference between RDN and sham)
Difference in 6-minute walk distance
Difference in 6-minute walk distance as compared to baseline
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)
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)
Change in Minnesota living with heart failure questionnaire
Change in Minnesota living with heart failure questionnaire, compared to baseline

Full Information

First Posted
August 30, 2021
Last Updated
April 25, 2023
Sponsor
University of Leipzig
Collaborators
ReCor Medical, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05030987
Brief Title
Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction
Acronym
UNLOAD-HFpEF
Official Title
Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction - A Single Center Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Leipzig
Collaborators
ReCor Medical, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Preserved Ejection Fraction, Hypertension, Renal
Keywords
Renal Denervation, Hypertension, Heart Failure with Preserved Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RDN
Arm Type
Experimental
Arm Description
Renal Denervation
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
Sham Procedure
Intervention Type
Procedure
Intervention Name(s)
Renal Denervation
Intervention Description
Renal denervation in patients with HFpEF and uncontrolled hypertension
Intervention Type
Procedure
Intervention Name(s)
Sham
Other Intervention Name(s)
Sham Procedure
Intervention Description
Sham Treatment. After six months, cross-over is planned in all sham-treated patients and this patients will also receive a renal denervation.
Primary Outcome Measure Information:
Title
exercise PCPW at 20 W workload
Description
To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment
Time Frame
6 months after randomization
Secondary Outcome Measure Information:
Title
number of combination of death, increase in diuretic therapy, hospitalization for heart failure, worsening NYHA-class, change in pulmonary pressure parameters
Description
number of combined endpoint in RDN and SHAM patients
Time Frame
6, 12 and 24 months after RDN
Title
Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements
Description
difference between RDN and sham
Time Frame
6 months after randomization
Title
Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements
Description
Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements, compared to baseline values
Time Frame
6, 12 and 24 months after RDN
Title
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
Description
difference between RDN and sham
Time Frame
6 months after randomization
Title
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
Description
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability, compared to baseline values
Time Frame
6, 12 and 24 months after RDN
Title
Difference in ventriculo-arterial coupling
Description
Difference in ventriculo-arterial coupling (by end-systolic elastance and arterial elastance) as acquired by invasive measurement
Time Frame
6 months after randomization
Title
Change in CMR-based hemodynamics
Description
Change in CMR-based hemodynamics (difference between RDN and sham) as compared to baseline values
Time Frame
6 months after randomization
Title
Change in ventriculo-arterial coupling
Description
Change in ventriculo-arterial coupling (cMRI and echocardiogram) (difference between RDN and sham) as compared to baseline values
Time Frame
6 months after randomization
Title
Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload)
Description
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
Time Frame
6 months after randomization
Title
Difference in peak PCWP
Description
Difference in peak PCWP (difference between RDN and sham) as compared to baseline values
Time Frame
6 months after randomization
Title
Difference in NT-proBNP
Description
Difference in NT-proBNP (difference between RDN and sham) as compared to baseline
Time Frame
6 months after randomization
Title
Difference in NT-proBNP
Description
Difference in NT-proBNP as compared to baseline
Time Frame
6, 12 and 24 months after RDN
Title
number of patients with Hospitalizations for heart failure
Description
number of patients with Hospitalizations for heart failure (difference between RDN and sham)
Time Frame
6 months after randomization
Title
difference in All-cause Mortality
Description
All-cause Mortality (difference between RDN and sham)
Time Frame
6 months after randomization
Title
difference in cardiac mortality
Description
cardiac mortality (difference between RDN and sham)
Time Frame
6 months after randomization
Title
difference in major adverse cardiovascular events
Description
major adverse cardiovascular events (composite of cardiac death, myocardial infarction, stroke and hospitalization for heart failure) (difference between RDN and sham)
Time Frame
6 months after randomization
Title
difference in number of Adverse Events
Description
Adverse events (difference between RDN and sham)
Time Frame
6 months after randomization
Title
difference in Frequency of patients with controlled hypertension
Description
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)
Time Frame
6 months after randomization
Title
difference in Frequency of patients with controlled hypertension
Description
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
Time Frame
6, 12 and 24 months after RDN
Title
Difference in 6-minute walk distance
Description
Difference in 6-minute walk distance (difference between RDN and sham)
Time Frame
6 months after randomization
Title
Difference in 6-minute walk distance
Description
Difference in 6-minute walk distance as compared to baseline
Time Frame
6, 12 and 24 months after RDN
Title
Change in exercise BP and maximum maximum exercise capacity
Description
Change in exercise BP between baseline and 6 months and maximum exercise capacity between baseline and 6 months (difference between RDN and sham)
Time Frame
6 months after randomization
Title
Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)
Description
Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)
Time Frame
6 months after randomization
Title
Change in Minnesota living with heart failure questionnaire
Description
Change in Minnesota living with heart failure questionnaire, compared to baseline
Time Frame
6, 12 and 24 months after RDN

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) 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%) NYHA-Class II or III Confirmation of an elevated cardiac filling pressures (either LVEDP >= 16 mmHg or PCWP >= 15 mmHg at rest or >=25 mmHg during exercise) by catheterization Age 18-80 years Written informed consent Exclusion Criteria: ≥1 main renal artery diameter <3.0 mm main renal artery length < 20 mm a single functioning kidney presence of abnormal kidney tumors renal artery aneurysm pre-existing renal stent or history of renal artery angioplasty fibromuscular disease of the renal arteries presence of renal artery stenosis of any origin ≥50% iliac/femoral artery stenosis precluding femoral access for RDN 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). participation in other interventional trials patients under legal supervision or guardianship suspected lack of compliance pregnant women Presence of intracardiac pacemakers or implantable cardioverter/defibrillators
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Philipp Lurz, Prof. Dr.
Phone
49 341
Ext
8651426
Email
philipp.lurz@medizin.uni-leipzig.de
First Name & Middle Initial & Last Name or Official Title & Degree
Karl Fengler, Dr. med.
Phone
49 341
Ext
8651427
Email
Karl.Fengler@medizin.uni-leipzig.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philipp Lurz, Prof. Dr.
Organizational Affiliation
Herzzentrum Leipzig, Universitätsklinik für Kardiologie
Official's Role
Study Chair
Facility Information:
Facility Name
Herzzentrum Leipzig, Universitätsklinik für Kardiologie
City
Leipzig
ZIP/Postal Code
04289
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philipp Lurz, MD, PhD
Email
philipp.lurz@medizin.uni-leipzig.de
First Name & Middle Initial & Last Name & Degree
Karl Fengler, MD, PhD
Email
karl.fengler@medizin.uni-leipzig.de

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
After publication of the major results and upon reasonable request from researchers performing an individual patient data meta-analysis, individual patient data that underlie published results will be shared after de-identification. This requires approval by the local Institutional Review Board (IRB) of the researcher requesting the data along with public registration of the meta-analysis. Summary statistics that go beyond the scope of published material will be made available to researchers for meta-analysis upon reasonable request and if the necessary data analysis is not unduly time-consuming. Together with publication of the main results, the trial protocol in full will be made publically available as well as the statistical analysis plan.
IPD Sharing Time Frame
after publication of the major results

Learn more about this trial

Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction

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