Heart Failure With Preserved Ejection FractionUNLOAD-HFpEFNCT05030987
Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction
A study testing Renal Denervation in people with Heart Failure With Preserved Ejection Fraction and Hypertension, Renal, run by University of Leipzig at 5 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Hypertension, Renal
- What is being tested?
- Renal Denervation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 5 sitesGermany
- Study dates
- 30 Nov 2021to 31 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 (European Society of Cardiology) 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
Who cannot join
- ≥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
Show all 15Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites, 5 recruiting
- Recruiting
BG Klinikum Unfallkrankenhaus Berlin gGmbH
Berlin, 13683
Sebastian Winkler, MD, PhD, +49 30 ext. 5681 3684, sebastian.winkler@ukb.de
Leonhard Bruch, MD, PhD, +49 30 ext. 5681 3601, leonhard.bruch@ukb.de
- Recruiting
Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin III
Halle, Saxony-Anhalt, 06120
Alexander Vogt, MD, PhD, +49 345 ext. 557 3134, alexander.vogt@uk-halle.de
- Not yet recruiting
Universitätsklinikum Leipzig, Klinik und Poliklinik für Kardiologie
Leipzig, 04103
Rolf Wachter, MD, Prof, +49 341 ext. 9720958, rolf.wachter@medizin.uni-leipzig.de
- Recruiting
Herzzentrum Leipzig, Universitätsklinik für Kardiologie
Leipzig, 04289
Karl Fengler, MD, PhD, karl.fengler@medizin.uni-leipzig.de
MD, PhD
- Recruiting
Universitätsmedizin der Johannes Gutenberg Universität Mainz, Zentrum für Kardiologie / Kardiologie 1
Mainz, 55131
Philipp Lurz, MD, Prof, +49 6131 ext. 177251, lurzphil@uni-mainz.de
Karl-Philipp Rommel, MD, PhD, rommelka@uni-mainz.de
About this study
Official title: Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction - A Pilot Trial
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.
Read the 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.
- Being tested
- Renal Denervation, Sham
- Keywords
- Renal Denervation, Hypertension, Heart Failure with Preserved Ejection Fraction
- Medical subject headings
- Hypertension, Renal, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Renal DenervationProcedure or surgery
Renal denervation in patients with HFpEF and uncontrolled hypertension
ShamProcedure or surgery
Also called Sham Procedure
Sham Treatment. After six months, cross-over is planned in all sham-treated patients and this patients will also receive a renal denervation.
| Study group | Role | What they receive |
|---|---|---|
| RDN | Experimental | Renal Denervation Receives: Procedure: Renal Denervation |
| Sham | Sham comparator | Sham Procedure Receives: Procedure: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload
To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment
Measured: 6 months after randomization
Secondary outcomes (24)
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
Measured: 6, 12 and 24 months after RDN
Change in mean Pulmonary artery (PA) pressure, estimated pulmonary artery diastolic pressure (ePAD) and PA pressure variability from pulmonary pressure sensor measurements
difference between RDN and sham
Measured: 6 months after randomization
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
Measured: 6, 12 and 24 months after RDN
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
difference between RDN and sham
Measured: 6 months after randomization
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
Measured: 6, 12 and 24 months after RDN
Difference in ventriculo-arterial coupling
Difference in ventriculo-arterial coupling (by end-systolic elastance and arterial elastance) as acquired by invasive measurement
Measured: 6 months after randomization
Change in Cardiac magnetic resonance (CMR) based hemodynamics
Change in CMR-based hemodynamics (difference between RDN and sham) as compared to baseline values
Measured: 6 months after randomization
Change in ventriculo-arterial coupling
Change in ventriculo-arterial coupling (cMRI and echocardiogram) (difference between RDN and sham) as compared to baseline values
Measured: 6 months after randomization
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
Measured: 6 months after randomization
Difference in peak PCWP
Difference in peak PCWP (difference between RDN and sham) as compared to baseline values
Measured: 6 months after randomization
Difference in NT-proBNP
Difference in NT-proBNP (difference between RDN and sham) as compared to baseline
Measured: 6 months after randomization
Difference in NT-proBNP
Difference in NT-proBNP as compared to baseline
Measured: 6, 12 and 24 months after RDN
number of patients with Hospitalizations for heart failure
number of patients with Hospitalizations for heart failure (difference between RDN and sham)
Measured: 6 months after randomization
difference in All-cause Mortality
All-cause Mortality (difference between RDN and sham)
Measured: 6 months after randomization
difference in cardiac mortality
cardiac mortality (difference between RDN and sham)
Measured: 6 months after randomization
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)
Measured: 6 months after randomization
difference in number of Adverse Events
Adverse events (difference between RDN and sham)
Measured: 6 months after randomization
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)
Measured: 6 months after randomization
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
Measured: 6, 12 and 24 months after RDN
Difference in 6-minute walk distance
Difference in 6-minute walk distance (difference between RDN and sham)
Measured: 6 months after randomization
Difference in 6-minute walk distance
Difference in 6-minute walk distance as compared to baseline
Measured: 6, 12 and 24 months after RDN
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)
Measured: 6 months after randomization
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)
Measured: 6 months after randomization
Change in Minnesota living with heart failure questionnaire
Change in Minnesota living with heart failure questionnaire, compared to baseline
Measured: 6, 12 and 24 months after RDN
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2021
- Study start30 Nov 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leipzig
- Sponsor type
- University, hospital or other
- Collaborators
- ReCor Medical, Inc.
- Responsible party
- Principal investigator, Karl Fengler, University of Leipzig
- Investigators
- Karl Fengler, PhD, Study chair, Herzzentrum Leipzig - Universitätsklinik für Kardiologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05030987
- Sponsor's protocol ID
- UNLOAD-HFpEF
- Other IDs
- CIV-20-10-034846
- Acronym
- UNLOAD-HFpEF
- Status last verified
- Jul 2024
- First submitted
- 30 Aug 2021
- Last updated
- 17 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction - A Pilot Trial
- ClinicalTrials.gov ID
- NCT05030987
- Acronym / sponsor ID
- UNLOAD-HFpEF / UNLOAD-HFpEF
- Keywords
- Renal Denervation, Hypertension, Heart Failure with Preserved Ejection Fraction
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- University of LeipzigUniversity, hospital or other
- Collaborators
- ReCor Medical, Inc.
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 1 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RDN | Experimental | Procedure: Renal DenervationRenal Denervation |
| Sham | Sham comparator | Procedure: ShamSham Procedure |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 (European Society of Cardiology) 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
Key exclusion criteria (15 listed)
- ≥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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Renal DenervationRenal denervation in patients with HFpEF and uncontrolled hypertension | Procedure or surgery | RDN |
| ShamAlso: Sham ProcedureSham Treatment. After six months, cross-over is planned in all sham-treated patients and this patients will also receive a renal denervation. | Procedure or surgery | Sham |
Primary outcome
exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload
Time frame: 6 months after randomization
To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment
24 secondary outcomes
number of combination of death, increase in diuretic therapy, hospitalization for heart failure, worsening NYHA-class, change in pulmonary pressure parameters
Time frame: 6, 12 and 24 months after RDN
Change in mean Pulmonary artery (PA) pressure, estimated pulmonary artery diastolic pressure (ePAD) and PA pressure variability from pulmonary pressure sensor measurements
Time frame: 6 months after randomization
Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements
Time frame: 6, 12 and 24 months after RDN
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
Time frame: 6 months after randomization
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability
Time frame: 6, 12 and 24 months after RDN
Difference in ventriculo-arterial coupling
Time frame: 6 months after randomization
Change in Cardiac magnetic resonance (CMR) based hemodynamics
Time frame: 6 months after randomization
Change in ventriculo-arterial coupling
Time frame: 6 months after randomization
Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload)
Time frame: 6 months after randomization
Difference in peak PCWP
Time frame: 6 months after randomization
Difference in NT-proBNP
Time frame: 6 months after randomization
Difference in NT-proBNP
Time frame: 6, 12 and 24 months after RDN
number of patients with Hospitalizations for heart failure
Time frame: 6 months after randomization
difference in All-cause Mortality
Time frame: 6 months after randomization
difference in cardiac mortality
Time frame: 6 months after randomization
difference in major adverse cardiovascular events
Time frame: 6 months after randomization
difference in number of Adverse Events
Time frame: 6 months after randomization
difference in Frequency of patients with controlled hypertension
Time frame: 6 months after randomization
difference in Frequency of patients with controlled hypertension
Time frame: 6, 12 and 24 months after RDN
Difference in 6-minute walk distance
Time frame: 6 months after randomization
Difference in 6-minute walk distance
Time frame: 6, 12 and 24 months after RDN
Change in exercise BP and maximum maximum exercise capacity
Time frame: 6 months after randomization
Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)
Time frame: 6 months after randomization
Change in Minnesota living with heart failure questionnaire
Time frame: 6, 12 and 24 months after RDN
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2024.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karl Fengler, PhD study chair
Herzzentrum Leipzig - Universitätsklinik für Kardiologie
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Renal Denervation in people with Heart Failure With Preserved Ejection Fraction and Hypertension, Renal, run by University of Leipzig at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Karl Fengler, PhD (49 341 ext. 8651426, Karl.Fengler@medizin.uni-leipzig.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload (time frame: 6 months after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2024.