Diastolic Heart FailurePhase 2/3DIASTOLENCT01583881
Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction
A Phase 2/3 study testing renal denervation in people with Diastolic Heart Failure and Hypertension, run by UMC Utrecht at 2 sites in Netherlands.
Trial summary
Increasing evidence suggests an important role of activation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal left ventricular ejection fraction and hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diastolic Heart Failure, Hypertension
- What is being tested?
- renal denervation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesNetherlands
- Study dates
- 1 Apr 2012to 1 Jul 2016
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individual is diagnosed with heart failure with a normal LV ejection fraction. The diagnosis of HFNEF requires the following conditions to be satisfied:
- signs or symptoms of heart failure;
- normal or mildly abnormal systolic LV function (LVEF ≥ 50%);
- evidence of diastolic LV dysfunction.
- Individual should fulfill the diagnostic WHO criteria for hypertension: SBP > 140 mmHg and/or DBP > 90 mmHg, and is treated with at least 2 antihypertensive drugs. This treatment is expected to be maintained for at least 6 months. Using this regimen the blood pressure should be adequately controlled (< 140/90mmHg by 24 hour ambulatory BP measurement).
- Individual is adhering to a stable drug regimen HFNEF, with no changes for a minimum of 2 weeks prior to enrollment, and which is expected to be maintained for at least 6 months.
- Individual is ≥ 18 years of age.
Who cannot join
- Known secondary cause of hypertension
- Anatomy not eligible for renal denervation
- Systolic heart failure (LVEF < 50%)
- Individual has an estimated glomerular filtration rate (eGFR) of < 30mL/min/1.73m2, using the MDRD calculation.
- Individual has any serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, haemophilia, significant anaemia, or arrhythmias such as atrial fibrillation).
- Individual is pregnant, nursing or planning to be pregnant.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Sympathetic Renal Denervation in Heart Failure With Normal LV Ejection Fraction: Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction
Increasing evidence suggests an important role of activation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal left ventricular ejection fraction and hypertension. The current study aims to evaluate efficacy and safety of renal sympathetic denervation for the modulation of the SNS in patients with heart failure with normal LV ejection fraction.
Read the detailed description
Rationale: Increasing evidence suggests an important role of activation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal left ventricular ejection fraction and hypertension. Moreover, sympathetic activation of the kidneys is directly proportional related to the severity of the heart failure state. Therapeutic renal denervation (PRDN), the deliberate disruption of the nerves connecting the kidneys with the central nervous system, has been shown to be an effective means of modulating elevated SNS activity. The current study aims to evaluate efficacy and safety of renal sympathetic denervation for the modulation of the SNS in patients with heart failure with normal LV ejection fraction.
Objective: Primary objectives: To investigate the efficacy of PRDN by means of pulsed wave Doppler echocardiographic parameters in patients diagnosed with HFNEF and hypertension. Secondary objectives: to investigate the safety of PRDN in patients with heart failure with normal LV ejection fraction and hypertension and to compare changes in the following parameters in patients with HFNEF and hypertension after PRDN: LV mass, LV volume, LA volume, LVEF, MIBG-uptake and -washout, BNP levels, blood pressure, heart rate variability, exercise capacity and quality of life.
Study design: Multicentre, prospective, randomised controlled trial. 60 patients will be randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment (n=30) or to maintain previous treatment alone (n=30) at 2 participating centres. Randomisation will be done with sealed envelopes.
Study population: Patients diagnosed with heart failure with normal LV ejection fraction and treated for hypertension. Patients should have a stable drug regimen, with at least 2 antihypertensive agents. This drug regimen should be expected to be maintained for at least 6 months.
Endpoints: The efficacy of PRDN will be evaluated primarily using echocardiographic parameters. Also, safety of PRDN on major and minor adverse events, LV mass, LV and LA dimensions, MIBG uptake and clinical endpoints will be evaluated.
- Conditions
- Diastolic Heart Failure, Hypertension
- Being tested
- renal denervation
- Keywords
- Patients with diastolic heart failure and hypertension
- Medical subject headings
- Heart Failure, Diastolic, 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
| Study group | Role | What they receive |
|---|---|---|
| Renal denervation | Experimental | Renal denervation Receives: Procedure: renal denervation |
| control | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline E/E' at 12 months
Echocardiography will be used to measure the E/E'
Measured: 12 months after treatment
Secondary outcomes (1)
Number of participants with adverse events
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2012 (estimated)
- Study start1 Apr 2012
- Primary completion1 Jun 2016
- Study completion1 Jul 2016
Why it stopped: Slow inclusion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diastolic Heart FailureStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- VU University of Amsterdam
- Responsible party
- Principal investigator, Michiel Voskuil, MD, PhD, UMC Utrecht
- Investigators
- Michiel Voskuil, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01583881
- Sponsor's protocol ID
- 12-046
- Acronym
- DIASTOLE
- Status last verified
- Apr 2021
- First submitted
- 19 Apr 2012
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Verloop WL, Beeftink MM, Nap A, Bots ML, Velthuis BK, Appelman YE, Cramer MJ, Agema WR, Scholtens AM, Doevendans PA, Allaart CP, Voskuil M. Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial. Eur J Heart Fail. 2013 Dec;15(12):1429-37. doi: 10.1093/eurjhf/hft119. Epub 2013 Jul 24.
PubMed 23883653
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sympathetic Renal Denervation in Heart Failure With Normal LV Ejection Fraction: Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction
- ClinicalTrials.gov ID
- NCT01583881
- Acronym / sponsor ID
- DIASTOLE / 12-046
- Conditions
- Diastolic Heart Failure, Hypertension
- Keywords
- Patients with diastolic heart failure and hypertension
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow inclusion
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- VU University of Amsterdam
- Study start
- 1 Apr 2012 (actual)
- Primary completion
- 1 Jun 2016 (actual)
- Study completion
- 1 Jul 2016 (actual)
- First posted
- 24 Apr 2012 (estimated)
- 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.
Increasing evidence suggests an important role of activation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal left ventricular ejection fraction and hypertension. The current study aims to evaluate efficacy and safety of renal sympathetic denervation for the modulation of the SNS in patients with heart failure with normal LV ejection fraction.
Detailed description
Rationale: Increasing evidence suggests an important role of activation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal left ventricular ejection fraction and hypertension. Moreover, sympathetic activation of the kidneys is directly proportional related to the severity of the heart failure state. Therapeutic renal denervation (PRDN), the deliberate disruption of the nerves connecting the kidneys with the central nervous system, has been shown to be an effective means of modulating elevated SNS activity. The current study aims to evaluate efficacy and safety of renal sympathetic denervation for the modulation of the SNS in patients with heart failure with normal LV ejection fraction.
Objective: Primary objectives: To investigate the efficacy of PRDN by means of pulsed wave Doppler echocardiographic parameters in patients diagnosed with HFNEF and hypertension. Secondary objectives: to investigate the safety of PRDN in patients with heart failure with normal LV ejection fraction and hypertension and to compare changes in the following parameters in patients with HFNEF and hypertension after PRDN: LV mass, LV volume, LA volume, LVEF, MIBG-uptake and -washout, BNP levels, blood pressure, heart rate variability, exercise capacity and quality of life.
Study design: Multicentre, prospective, randomised controlled trial. 60 patients will be randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment (n=30) or to maintain previous treatment alone (n=30) at 2 participating centres. Randomisation will be done with sealed envelopes.
Study population: Patients diagnosed with heart failure with normal LV ejection fraction and treated for hypertension. Patients should have a stable drug regimen, with at least 2 antihypertensive agents. This drug regimen should be expected to be maintained for at least 6 months.
Endpoints: The efficacy of PRDN will be evaluated primarily using echocardiographic parameters. Also, safety of PRDN on major and minor adverse events, LV mass, LV and LA dimensions, MIBG uptake and clinical endpoints will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Renal denervation | Experimental | Procedure: renal denervationRenal denervation |
| control | No intervention | –No intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Individual is diagnosed with heart failure with a normal LV ejection fraction. The diagnosis of HFNEF requires the following conditions to be satisfied:
- Individual should fulfill the diagnostic WHO criteria for hypertension: SBP > 140 mmHg and/or DBP > 90 mmHg, and is treated with at least 2 antihypertensive drugs. This treatment is expected to be maintained for at least 6 months. Using this regimen the blood pressure should be adequately controlled (< 140/90mmHg by 24 hour ambulatory BP measurement).
- Individual is adhering to a stable drug regimen HFNEF, with no changes for a minimum of 2 weeks prior to enrollment, and which is expected to be maintained for at least 6 months.
- Individual is ≥ 18 years of age.
Key exclusion criteria (6 listed)
- Known secondary cause of hypertension
- Anatomy not eligible for renal denervation
- Systolic heart failure (LVEF < 50%)
- Individual has an estimated glomerular filtration rate (eGFR) of < 30mL/min/1.73m2, using the MDRD calculation.
- Individual has any serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, haemophilia, significant anaemia, or arrhythmias such as atrial fibrillation).
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 | Procedure or surgery | Renal denervation |
Primary outcome
Change from baseline E/E' at 12 months
Time frame: 12 months after treatment
Echocardiography will be used to measure the E/E'
1 secondary outcome
Number of participants with adverse events
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Slow inclusion). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Derived from this study: PubMed 23883653Verloop WL, Beeftink MM, Nap A, Bots ML, Velthuis BK, Appelman YE, Cramer MJ, Agema WR, Scholtens AM, Doevendans PA, Allaart CP, Voskuil M. Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial. Eur J Heart Fail. 2013 Dec;15(12):1429-37. doi: 10.1093/eurjhf/hft119. Epub 2013 Jul 24.
Related trials for Diastolic Heart Failure
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 1
A Study of LY3971297 in Participants With Heart Failure
Heart Failure, Heart Failure, Diastolic
Not yet recruiting
Importance of Point-of-Care Ultrasound for Early Detection of Valvular and Cardiac Diseases (IMPROVE)
Valvular Heart Disease Patients, Aortic Stenosis
Recruiting
PrEcision Pacing in HFpEF: the PEP-HFpEF Trial
Heart Failure and Preserved Ejection Fraction, Heart Failure New York Heart Association Class III
Recruiting
Assessment of CCM in HF With Higher Ejection Fraction
Heart Failure, Heart Failure With Preserved Ejection Fraction
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.
Michiel Voskuil, MD, PhD principal investigator
UMC Utrecht
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing renal denervation in people with Diastolic Heart Failure and Hypertension, run by UMC Utrecht at 2 sites in Netherlands.
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 7 inclusion and 6 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: stopped early, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow inclusion). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline E/E' at 12 months (time frame: 12 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01583881, which also lists 1 linked publication.
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 3 May 2021.