To test the efficacy of renal sympathetic denervation therapy with a special focus on preservation of renal allograft function.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Renal and urinary tract therapeutic procedures
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is blood pressure reduction after 6 months (day time blood
pressure assessed by 24-hours ambulatory measurement).
Secondary outcome
- Change in 123I-metaiodobenzylguanidine (123I-MIBG) uptake of native kidneys
(i.e. effectiveness of denervation)
- Change in systemic sympathetic activity and plasma rennin and aldosterone
activity
- Change in proteinuria after 6 months.
- Change in creatinine clearance after 6 months.
- Change in eGFR
- Change in number of antihypertensive drugs.
- Change in health related quality of life.
Background summary
In patients with a renal allograft, hypertension is a major etiological factor
for cardiovascular morbidity, mortality and allograft nephropathy. Controlling
hypertension in patients with a renal allograft is therefore crucial. There is
a pressing, yet currently unmet clinical need for new blood pressure lowering
strategies in renal allograft recipients.
The diseased native kidneys are major contributors to hypertension, through
neuro-hormonal up-regulation that leads to high levels of renin and sympathetic
activity. Recently a catheter-based approach has been developed to disrupt
renal sympathetic nerves. Currently this innovative technique has only been
tested to lower blood pressure in therapy resistant hypertensive patients
without significant renal disease.
We hypothesize that catheter based selective renal denervation of the native
kidneys in renal transplant recipients will improve blood pressure control and
diminish the number of antihypertensive drugs.
Study objective
To test the efficacy of renal sympathetic denervation therapy with a special
focus on preservation of renal allograft function.
Study design
We propose a randomized controlled clinical trial (intervention group n=20;
controls n=20). Intervention and control groups will receive standard
protocolized antihypertensive treatment prior to, and during the trial. The
interventiongroup will receive renal denervation in addition to standard
treatment.
Intervention
Prior to study-inclusion all patients will receive standard protocolized
hypertension treatment based on the National Kidney Foundation Kidney Disease
Quality Outcomes Quality Initiative guidelines (2004). Renal sympathetic
denervation is achieved by the interventional radiologist percutaneously
entering the lumen of the main renal artery of each of the native kidneys, with
a catheter connected to a radiofrequency generator. He applies 6-8
radiofrequency ablations within each renal artery. The procedure is performed
in an outpatient clinic setting.
Study burden and risks
- The risks of femoral artery catheterisation are bleeding, infection and
contrast-agent induced nephropathy.
- The risk of the venous canulation (for the 123I-MIBG scintigraphy, and for
drawing blood) is haematoma formation, and infection.
- The direct burden of the ablation procedure is that it causes visceral pain
(from the local heat of the radiofrequency probe) that will be treated with
appropriate analgesics. The benefits of renal denervation are an expected
lowering of blood pressure and thereby improved graft survival and
cardiovascular co-morbidity risk and a reduction in the number of
anti-hypertensives needed.
- The total amount of radio-contrast agent administered during the
catheterisation is < 100 ml. The risk of contrast induced (allograft)
nephropathy is minimized by pre- and post-hydration.
- Time burden: patients with a kidney transplant attend their nephrologist on
average 4 times a year. The number of extra (outpatient) clinic visits for
participation in this study is 2 (a 30 minutes) for the control group and 10
for the intervention group:
o 5 of 30 minutes: outpatient clinic visits and second day 123-I-MIBG scanning
o 2 of 4,5 hours: first day 123-I-MIBG scanning
o 2 of 2 hours: peroneal microneurography and
o 1 of 8 hours: for denervation procedure with pre and post-hydration.
- There are no known risks to the extra (ambulatory) blood pressure
measurements.
- The total amount of blood taken in addition to standard care amounts to 20 ml
for the patients in the control group and 70 ml for the patients in the
intervention group.
- The total radiation exposure for patients in the intervention group due to
123I-MIBG amounts to 2 * 5,1 mSv and due to the ablation procedure to an
estimated 0,7 mSv. The complete radiation exposure amounts to 11 mSv.
- The risk from the microneurography is the occurrence of temporary minor
paresthesias at the site of probing in the weeks after the study [25]. This
risk is thought to be very low (< 1 %). This risk is considered acceptable
given the valuable data that this technique provides that can not be acquired
otherwise.
From the introduction it is evident that the risks and burden for the patients
are in proportion to the potential value of the research and the benefit that
the patients in the intervention group may have. For the patients in the
control group, there is a group related benefit.
Meibergdreef 9
1105AZ Amsterdam 1105AZ
NL
Meibergdreef 9
1105AZ Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- renal graft in situ since > 6 months, measured creatinine clearance > 35 ml/min, and
- diuresis of the native kidneys at transplant >200 ml/day or radiological evidence of residual flow in the renal arteries indicating that they are accessible for the intervention and
- day time blood pressure >140/90 mmHg (assessed by 24-hours ambulatory measurement within 3 month prior to inclusion in the study, as is regularly performed in the nephrology outpatient clinic) while
- treated according to National Kidney Foundation Kidney Disease Quality Outcomes Quality Initiative guidelines (2004), i.e. having been advised to minimize salt intake and using >3 antihypertensive medications in maximal tolerated dose, including a diuretic. Medications and their dosages should not have been changed since the measurement.
Exclusion criteria
- (planned) pregnancy, lactation
- life expectancy < 1 year
- non-functioning renal allograft in situ
- contraindications for (relative) hypotensive episodes i.e. haemodynamically significant valvular disease, documented transient ischemic attacks or angina pectoris during relative hypotension.
- heart failure, NYHA class III-IV; chronic Lung Disease Gold III-IV
- major complications during previous radiological interventions (i.e. allergy to contrast agent, cholesterol embolism)
- (reno) vascular abnormalities in any part of the catheter access (including the aortic-ileac tract) route that impede the procedure of renal denervation
- use of vitamine K antagonists or other (non-aspirin) form of anti-coagulatory therapy with an absolute indication (i.e. that cannot be temporarily stopped)
- implantable cardioverter defibrillator (ICD) in situ
- planned surgery within the next six months.
- Drugs- or alcohol abuse
- Inability to give informed consent
Design
Recruitment
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 | NCT:TC2998 |
| CCMO | NL37711.018.11 |