The main purpose of this study is to assess the impact of arterial stiffness on the response in 24h ambulatory blood pressure reduction following renal sympathetic denervation in patients with primary hypertension with or without diastolic…
ID
Source
Brief title
Condition
- Heart failures
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
To assess the predictive value of arterial stiffness measured by MRI on the
blood pressure response to renal artery denervation in patients with or without
diastolic dysfunction using 24h ambulant blood pressure monitoring.
Primary safety endpoint
The occurrence of cardiovascular death, major access site bleeding, acute
kidney injury and renal artery stenosis at 6 months.
Secondary outcome
1. To evaluate the change in arterial stiffness at baseline vs. 6 and 12 months
post procedure.
2. To assess the impact of diastolic function using echo at baseline on the
blood pressure response to renal artery denervation.
3. To assess the change in left ventricular volume and diastolic function
following renal artery denervation.
4. To assess the change in renal perfusion at baseline vs. 6 and 12 months post
procedure
5. To assess the change in blood pressure pre- vs. post procedure using 24h
ambulatory blood pressure measurement.
6. Acute procedural safety (defined as the absence of peri-procedural safety
endpoints)
7. The individual items of the primary safety endpoint.
8. Newly acquired renal artery stenosis and/or repeat renal artery intervention.
9. Development of renal failure and/or requirement of dialysis
10. Hospitalization for hypertensive emergency.
Background summary
The estimated incidence of hypertension in the general population is estimated
to be between 30 and 40% and suboptimal blood pressure control is the largest
contributor to death worldwide. Despite the prevalence of hypertension and its
associated complications, control of the disease is far from adequate. The
prevalence of therapy resistant hypertension reaches up to 25% of all
hypertensive patients treated in Europe. Increased sympathetic nervous system
(SNS) activity has been documented in systolic-diastolic and isolated systolic
hypertension, in white coat and masked hypertension and pregnancy induced
hypertension by using sophisticated techniques for measuring adrenergic
activity. Furthermore, SNS activity increases progressively and in parallel
with hypertensive stages. The contribution of the kidney*s somatic afferent
nerves, as an underlying cause of elevated central sympathetic drive, and the
consequences of excessive efferent sympathetic signals to the kidney itself, as
well as other organs, identify the renal sympathetic nerves as a logical
therapeutic target for diseases linked by excessive central sympathetic drive.
Renal sympathetic denervation is an emerging technology for the treatment of
therapy resistant hypertension. By one single invasive procedure taking about
45 minutes, approximately 6 radiofrequency ablations will be delivered to each
renal artery. Previous studies already showed that the technology is safe and
effective. Nevertheless, despite the fact that almost all patients did show a
significant reduction in blood pressure after 1 to 2 years of follow-up, there
seems be an apparent inter-individual difference in the treatment effect.
In recent years, great emphasis has been placed on the role of arterial
stiffness in the development of cardiovascular diseases. More specifically,
arterial stiffening has been identified as a marker for increased
cardiovascular disease risk and is increasingly used as a parameter in the
clinical assessment of patients.
Study objective
The main purpose of this study is to assess the impact of arterial stiffness on
the response in 24h ambulatory blood pressure reduction following renal
sympathetic denervation in patients with primary hypertension with or without
diastolic dysfunction. In addition, the effect of renal denervation on arterial
stiffness and diastolic function will be assessed.
Study design
Two-arm study of patients with primary hypertension and a systolic blood
pressure of 160 mmHg or more despite the use of at least three antihypertensive
drugs (including one diuretic). Arm 1 will include 15 patients with diastolic
dysfunction; arm 2 will include 15 patients without diastolic dysfunction.
In order to assess the natural evolvement in aortic stiffness in patients not
undergoing renal denervation 5 patients out of both group will undergo standard
analyses including MRI at screening and at 6 months without having been
treated. This cohort of 10 patients will undergo renal denervation at 6 months
and will be followed in a similar manner as those having received the treatment
at baseline. Yearly follow-up will be continued up until 5 years.
Intervention
Placed percutaneously, the Simplicity renal denervation catheter will be
advanced into the renal artery using a routine femoral artery approach in a
cardiac catheterization laboratory setting. Radiofrequency ablation will be
applied by using an automated programmed algorhythm (pre-programmed time and
intensity)
Study burden and risks
Patients will undergo thorough pre-procedure assessment and imaging assessment
(both MRI ultrasound) prior to selection and inclusion into the study. The
procedure is initiated by puncture of the femoral artery with its inherent
risks including bleeding, aneurysm formation, dissection, thrombosis and
perforation. However, these risks are not different from each comparable form
of angiography in which the groin is punctured and the access procedure is
known for its low and acceptable complication risk. An additional potential
procedure risk is caused by the radiofrequency ablation of the renal artery
with focal damage of the endothelium on the coagulation spots. However, study
data thus far do not show any signs of arterial damage due to the ablation
procedure.
Based on previous studies using the Simplicity renal denervation system in
approximately 350 patient, the following complications were recorded:
- damage to the blood vessels of the kidney in approximately 1% of the patients
- blood clots leading to heart attach or stroke in approximately 1-2%
- extended hospital stay in 1-2%
- pseudoaneurysm of the femoral artery in approximately 1-2% of the patients
- (temporarily) low blood pressure in 1-2% of the patients
- urinary tract infection in 1-2% of the patients
- renal artery stening in 1-2% of the patients
- arrhythmias during the procedure in 1-2%
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
1. Age >=18 years;
2. Systolic blood pressure of 160 mmHg or more despite the use of at least
three antihypertensive drugs (including one diuretic);
3. Presence of diastolic dysfunction at baseline in 50% of the population.
4. A glomerular filtration rate of 45ml/min/1.73m2 or more;
5. Written informed consent;
6. The patient agrees to the follow-up including the imaging modalities;
Exclusion criteria
1. Pregnancy;
2. Renal artery abnormalities;
3. Known secondary causes of hypertension with the exception of obstructive
sleep apnea syndrome;
4. General MRI contra-indications (Appendix I);
5. The patient has other medical illness (i.e., cancer or congestive heart
failure) that may cause the patient to be non-compliant with the protocol,
confound the data interpretation or is associated with limited life expectancy
(i.e., less than one year);
6. A mean systolic blood pressure of less than 135mmHg pre procedure by 24h
ambulatory blood pressure measurement;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42280.078.12 |