The purpose of this Clinical investigation is to further evaluate the safety and performance of the EnligHTN* Renal Denervation System in the treatment of patients with uncontrolled hypertension.
ID
Source
Brief title
Condition
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to evaluate a mean reduction in office Systolic Blood
Pressure at six (6) months across all subjects post renal denervation and
within sub-groups.
Secondary outcome
The secondary objectives are:
1. Safety
Acute (30 days post procedure):
* The assessment of peri-procedural events
Midterm (6 months):
* Assessment of renovascular safety as measured by new renal artery stenosis
or aneurysm at the site of ablation
* Renal function change based on eGFR
Long term (2 and 5 years):
* Assessment of renovascular safety as measured by new renal artery stenosis or
aneurysm at the site of ablation
* Renal function change based on eGFR
2. BP reduction
* Change in Ambulatory Blood Pressure parameters at 6 months
* Change in office Diastolic Blood Pressure at 6 months
* Percentage of subjects achieving office Systolic Blood Pressure < 140mmHg at
6 month visit
*Change in Office and Ambulatory Blood Pressure parameters at 12, 24, 36, 48,
60 months post denervation
Background summary
Hypertension or high blood pressure is a major risk factor for cardiovascular
and cerebrovascular events. It is responsible for approximately one half of
the coronary heart disease and two thirds of the cerebrovascular disease
burdens. It is also the world*s number one attributable risk for death. The
global prevalence of hypertension has been increasing. An analysis indicated
that more than one quarter (nearly one billion) of the world*s adult population
had hypertension in 2000. This is projected to increase to 1.56 billion
affected individuals with a prevalence rate of 29% in 2025. This is a major
public health challenge in both economically developing and developed countries.
Previous studies showed that drug therapy may reduce the risk of major
cardiovascular events by about 20% and the risk of stroke by about 40% in
patients with hypertension. However, these may not apply to all patients with
hypertension. A large proportion of patients with hypertension still remains
untreated or uncontrolled due to many factors. For patients with resistant
hypertension despite the use of aggressive drug therapy, which includes at
least 3 anti-hypertensive drugs with a diuretic being one of these drugs, blood
pressure management remains uncontrolled. In the general hypertensive
population, the prevalence of resistant hypertension is estimated to be about
5% to 12%. In patients with co-morbidity, such as chronic renal failure or
diabetes, the prevalence of resistant hypertension is even significantly
higher. Hypertension is also mainly an symptomatic disease, which could be
difficult to have the patient understanding about the importance of complying
and adhering to the lifelong drug therapy. Alternative approaches to control
the blood pressure of these patients are urgently needed.
The kidneys represent the central homeostatic organ regulating blood pressure
and blood volume. Previous experimental functional studies showed that renal
denervation could reduce the norepinephrine level of up to 95%. In various
experimental models the magnitude of the hypertension has been reduced and the
renal blood flow has been increased during the observation period after renal
denervation.
Percutaneous catheter-based methods deliver radiofrequency (RF) energy to the
renal sympathetic nerves for the ablation-induced renal denervation. This
minimally invasive and more localized approach allows for possibly much shorter
procedural time, shorter hospital stay and shorter recovery time, which may
benefit more patients with uncontrolled hypertension.
Recent clinical studies reported significant improvement of office blood
pressure measurement in patients with resistant hypertension after the
catheter-based renal denervation procedure (about -20/-10 mmHg, -25/11 mmHg,
-23/-11 mmHg and -32/-14 mmHg at 1, 6, 12 and 24 months respectively from
baseline systolic/diastolic blood pressures).
EnligHTN-I (ARSENAL) was a feasibility study to demonstrate the safety and
efficacy of the St. Jude Medical Radiofrequency Renal Denervation System in the
treatment of patients with resistant hypertension. Subjects will be followed
for 24 months post procedure. This clinical data shows that the average
systolic / diastolic Blood Pressure between baseline and one month was -28/-10
mmHg with 78% of the patients experiencing a * 10 mmHg reduction in systolic
Blood Pressure. After three months this difference was -27/-10 mmHg with 80% of
the patients experiencing a * 10 mmHg reduction in systolic Blood Pressure.
The mean systolic/diastolic ambulatory Blood Pressure difference between
baseline and 3 months was -9.9/-5.4 mmHg. Recently the 6 month data was
presented; the difference was -27/-10 mmHg and -10,3/-5,7 in systolic
ambulatory Blood Pressure.
Study objective
The purpose of this Clinical investigation is to further evaluate the safety
and performance of the EnligHTN* Renal Denervation System in the treatment of
patients with uncontrolled hypertension.
Study design
This is a post market, prospective, multicenter, non-randomized, single arm
study of the EnligHTN* Renal Denervation System. Approximately 500 subjects
with uncontrolled hypertension will undergo renal artery ablation at
approximately 40 investigational sites located internationally and will be
followed up to five (5) years post procedure.
Study burden and risks
Having blood taken may cause some discomfort or bruising. Sometimes, the blood
vessel may swell, or blood may clot in the blood vessel, or the spot from which
blood is taken could become inflamed. Rarely, there could be a minor infection
or bleeding. If this happens, it can be easily treated.
The renal denervation is an interventional approach, and as such carries some
potential risks, which may include but are not limited to the following:
*Acute renal injury such as unintended renal tissue damage or bruising
*Injury to the renal arteries such as a tear in the lining of the artery,
formation of a blood clot or narrowing of the artery
*Bleeding
*Injury to the tissues surrounding the renal arteries
*Worsening of high blood pressure
*Low blood pressure that may result in feeling light headed, faint or dizzy
*Injury at the site of catheter insertion such as:
o The formation of an abnormal connection between an artery and vein resulting
in abnormal blood flow
o The formation of a blood clot
o The obstruction of a blood vessel by an air bubble, foreign object or blood
clot
o Bulging of an artery due to injury to one or more of its layers
o Bruising
o Decreased blood flow and oxygen to the limb
o Damage to the nerve in the thigh
o Accumulation and seeping of cellular fluid at the insertion site
*Formation of small blood clots inside the blood vessels throughout the body
(disseminated intravascular coagulation)
*Temporary very slow heart beat during the procedure
*Pain (including back pain)
*Unintended reactions to the drugs used during the procedure
*Allergic reaction due to contrast media injected during the procedure
*Infection (at the site of catheter insertion or throughout the body)
*Renal failure
*Worsening of heart failure
*Heart attack
*Stroke
*Difficulty breathing
*Death
*Blood vessels spasms (vasospasms)
*Discomfort which may lead to fainting (vasovagal episodes)
When you have a CT scan or renal artery angiogram, you will be exposed to
radiation. This research study involves exposure to a small amount of
radiation. As part of everyday living, everyone is exposed to naturally
occurring background radiation and receives a dose of about 2 millisieverts
(mSv) each year. The effective dose from this study is about 25 mSv. The dose
from this study is comparable to that received from several computed tomography
x-ray (CT) and nuclear medicine procedures. The benefits from the study should
be weighed against the possible detrimental effects of radiation, including an
increased risk of fatal cancer. In this particular study, the risk is moderate
and the estimated risk of such harm is about 1 in 800. For comparison, this
risk is about 200 times lower than the cancer mortality rate in the general
population of about one case in every four people.
The effects of renal denervation procedure on the unborn child and on the
newborn baby are not known. Because of this, it is important that study
participants are not pregnant or breast-feeding and do not become pregnant
during the course of the research project. You must not participate in the
research if you are pregnant or trying to become pregnant, or breast-feeding.
If you are female and child-bearing is a possibility, you may be required to
undergo a pregnancy test prior to commencing the research project.
There may be other risks that are not known at this time.
Standaardruiter 13
VEENENDAAL 3905 PT
NL
Standaardruiter 13
VEENENDAAL 3905 PT
NL
Listed location countries
Age
Inclusion criteria
- Subject is * 18 years of age at time of consent
- Subject must be able and willing to provide written informed consent
- Subject must be able and willing to comply with the required follow-up schedule
- Subject has office Systolic Blood Pressure * 140 mmHg at confirmatory visit
- Subject has a daytime mean Systolic Ambulatory Blood Pressure > 135 mmHg within 90 days prior to enrollment
- Subject has established hypertension (diagnosed *12 month prior to baseline) and on a stable, guideline based drug regimen consisting of * 3 anti-hypertensive medications (must include 1 diuretic) or subject has a documented drug(s) intolerance.
Exclusion criteria
- Subject has significant renovascular abnormalities such as renal artery stenosis > 30%
- Subject has undergone prior renal angioplasty, renal denervation, indwelling renal stents, and/or abdominal aortic stent grafts
- Subject has hemodynamically significant valvular heart disease as determined by study investigator
- Subject has a life expectancy less than 12 months, as determined by the Investigator
- Subject is participating in another clinical study which has the potential to impact their hypertension management (pharmaceutical/device/homeopathic)
- Subject is pregnant, nursing, or of childbearing potential and is not using adequate contraceptive methods
- Subject has active systemic infection
- Subject has renal arteries with diameter(s) < 4 mm in diameter
- Subject has an estimated GFR <15 mL/min per 1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula
- Subject had a renal transplant or is awaiting a renal transplant
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 |
|---|---|
| ClinicalTrials.gov | NCT01705080 |
| CCMO | NL42560.041.13 |