To assess the short-term and long-term safety and efficacy of bilateral ultrasound renal sympathetic denervation (RDN) of the native kidneys in renal transplant patients with uncontrolled hypertension.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change in systolic mean 24-hour ambulatory BP between baseline and the
3-months following the RDN procedure.
Secondary outcome
The most important secondary study outcomes involve:
- Composite safety endpoint consisting of the occurrence of any of the
following events before the 3-month follow-up visit (F3): all-cause mortality,
new onset (acute) end-stage renal disease, significant embolic event resulting
in end-organ damage, renal artery perforation requiring an invasive
intervention, renal artery dissection requiring an invasive intervention, major
vascular complications requiring surgical repair, interventional procedure,
thrombin injection, or blood transfusion or hospitalization for hypertensive or
hypotensive crisis.
- The change in diastolic mean 24-hour ambulatory BP between baseline (V1) and
the 3-month follow-up visit (F3)
- The change in systolic and diastolic daytime and nighttime ambulatory BP
between baseline (V1) and the 3-month follow-up visit (F3)
- The change in systolic and diastolic office BP between baseline (V1) and the
3-month follow-up visit (F3)
- The change in systolic and diastolic average home BP between baseline (V1)
and the 3-month follow-up visit (F3)
- The change in systolic and diastolic mean 24-hour, daytime and nighttime
ambulatory BP between baseline (V1) and the 3-month follow-up visit (F3) in
patients with adherence to the same antihypertensive drugs (as based on serum
therapy adherence testing) at both time points
- The change in systolic and diastolic office BP between baseline (V1) and the
3-month follow-up visit (F3) in patients with adherence to the same
antihypertensive drugs (as based on serum adherence testing) at both time points
- The change in systolic and diastolic average home BP between baseline (V1)
and the 3-month follow-up visit (F3) in patients with adherence to the same
antihypertensive drugs (as based on serum adherence testing) at both time points
- The change in prescribed antihypertensive drugs (displayed as the number of
DDDs and number of classes) between baseline and 3 months (F3)
- The change in therapy adherence (defined as the percentage of prescribed
drugs that can be detected using serum adherence testing) between baseline and
3 months (F3)
- The annual change in systolic and diastolic mean 24-hour, daytime and
nighttime ambulatory BP up until 5-year follow-up (F60)
- The annual change in systolic and diastolic office BP up until 5-year
follow-up (F60)
- The annual change in systolic and diastolic average home BP up until 5-year
follow-up (F60)
- The change in prescribed antihypertensive drugs (displayed as the number of
DDDs and number of classes) up until 5-year follow-up (F60)
- The change in therapy adherence (defined as the percentage of prescribed
drugs that can be detected using serum adherence testing) up until 1-year
follow-up (F12)
- The number of patients in whom no successful bilateral RDN procedure can be
performed (e.g. due to anatomical difficulties)
- The change in renal function (eGFR) and proteinuria (protein/creatinine
ratio) between baseline (V1) and the 3-month follow-up visit (F3)
- The occurrence of the individual components of the composite safety outcome
up until 5-year follow-up (F60)
- The occurrence of any major adverse cardiovascular and cerebrovascular event
(MACCE) up until 5-year follow-up (F60), including myocardial infarction,
coronary revascularization, stroke and cardiovascular mortality
- The occurrence of any individual components of MACCE up until 5-year
follow-up (F60)
- The occurrence of all-cause mortality up until 5-year follow-up (F60)
- The change in renal function (eGFR) and proteinuria (protein/creatinine
ratio) over time up until 5-year follow-up (F60)
Background summary
Uncontrolled hypertension is present in 5-20% of all patients with a history of
renal transplantation resulting in a significantly increased risk for
cardiovascular, as well as kidney allograft disease. The residual hormonal
function of the native kidneys is hypothesized to be a key contributor to this
problem. The efficacy and safety of percutaneous native kidney denervation in
patients post kidney transplantation has not been sufficiently studied.
Study objective
To assess the short-term and long-term safety and efficacy of bilateral
ultrasound renal sympathetic denervation (RDN) of the native kidneys in renal
transplant patients with uncontrolled hypertension.
Study design
Interventional single-center, single-arm, proof-of-concept study.
Intervention
Conventional angiography and bilateral ultrasound RDN of the native renal
arteries.
Study burden and risks
Patients will need to comply to eight outpatient clinic visits and a single
one-night hospital admission throughout their five-year study participation.
The intervention studied (i.e. native kidney RDN) is considered a very low-risk
procedure which should theoretically outweigh the risks of the (improvement in)
known detrimental effects of uncontrolled BP on morbidity and mortality.
Throughout the course of the study, magnetic resonance imaging will be
performed at screening and ambulatory BP measurements will be performed six
times. Blood sampling and therapy adherence testing (using dried blood spot
sampling) will be performed eight and seven times, respectively.
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. Kidney transplantation >= 9 months ago with stable immunosuppressive drug
treatment (dosage changes to maintain a steady serum concentration are
permitted)
3. Estimated Glomerular Filtration Rate (eGFR) >= 30 ml/min/1.73m2
4. Office systolic blood pressure >= 140 mmHg at screening (V0), and a systolic
mean 24-hour ambulatory blood pressure >= 130 mmHg (V1)
5. With respect to antihypertensive medication:
a. Patients should be on a stable regimen of at least two antihypertensive
drugs of different classes, for at least six weeks, or
b. Patients should have a documented intolerance to three classes of
antihypertensive drugs.
Patients should only be included when a change in antihypertensive drug regimen
is not anticipated within the oncoming three months.
6. Patient is willing and able to provide written informed consent
Exclusion criteria
• Native renal artery anatomy not eligible for renale denervatie, defined as at
least one of the following conditions: o History of renal artery stenting or
angioplasty o History of renal denervation o History of kidney tumors o Renal
artery diameter < 3 mm or > 8 mm o Renal artery length < 20 mm o Fibromuscular
disease (FMD) of the native renal arteries o Renal artery aneurysm o Renal
artery stenosis > 30% • Presence of a remnant transplant kidney after
re-transplantation or absence of native kidneys • History of intravenous
contrast dye allergy or nephropathy • Iliac/femoral artery stenosis precluding
insertion of the Paradise catheter • Uncorrected, treatable secondary cause of
hypertension • Pregnancy • Life expectancy < one year at the discretion of the
investigator
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 |
|---|---|
| Other | ClinicalTrials.gov (in afwachting publicatie) |
| CCMO | NL84285.078.23 |