Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction

Hypertension Clinical Trial

— DIASTOLE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01583881
• Other study ID #: 12-046
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: April 1, 2012
• Est. completion date: July 1, 2016

Study information

• Verified date: April 2021
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: July 1, 2016
• Est. primary completion date: June 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Diastolic Heart Failure
• Heart Failure
• Heart Failure, Diastolic
• Hypertension

Intervention

Procedure:
• renal denervation
Renal denervation

Locations

Country	Name	City	State
Netherlands	VUmc	Amsterdam
Netherlands	UMC Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	VU University of Amsterdam

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline E/E' at 12 months	Echocardiography will be used to measure the E/E'	12 months after treatment
Secondary	Number of participants with adverse events		1 year