The primary objective is to investigate if there is an incremental inhibiting effect on MSNA by increasing dosage valsartan above the presently advised dosage. We hypothesize that there will be a further decrease in MSNA as compared to the MSNA…
ID
Source
Brief title
Condition
- Other condition
- Nephropathies
Synonym
Health condition
Hypertensie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint/outcome
- Primary endpoint: the effect of increasing dosage of valsartan on MSNA
- Primary expected outcome: further decrease in MSNA as compared to the MSNA
during standard dosage
Secondary outcome
Secondary endpoint/outcome
1. Secondary endpoint: assessment of normalization of MSNA after application of
higher than usual dosage of valsartan
- Secondary expected outcome: normalization of MSNA after application of higher
than usual dosage of valsartan
2. Effect of higher than usual dosage of valsartan on blood pressure
- Secondary outcome: higher than usual dosage of valsartan will not
have a further effect on blood pressure
Background summary
Cardiovascular (CV) morbidity and mortality are frequently occurring problems
in chronic kidney disease (CKD) patients. Apart from the so called traditional
risk factors, also risk factors more or less specific to CKD contribute in the
pathogenesis of these problems. There is strong evidence that the sympathetic
hyperactivity, which often characterizes CKD, is one such factor. Previously,
we have shown that angiotensin converting enzyme inhibitors (ACEi) and
angiotensin II receptor blockers (ARB) reduce but not normalize this
sympathetic hyperactivity. We re-analysed the cohort of patients who were
investigated in the past and subsequently treated according to present
guidelines. The results show that, despite of treatment, the unfavourable
relation between sympathetic hyperactivity and clinical outcome still exits.
This might mean that treatment is insufficient and need to be improved.
Study objective
The primary objective is to investigate if there is an incremental inhibiting
effect on MSNA by increasing dosage valsartan above the presently advised
dosage.
We hypothesize that there will be a further decrease in MSNA as compared to the
MSNA during standard dosage valsartan.
Study design
This study is designed as a randomized cross-over trial. We prospectively
collect data on activity of MSNA at different stages of treatment by high
dosage of valsartan. It will be done in hypertensive CKD patients irrespective
of renal function as sympathetic activity is not related to kidney function.
However, patients on renal replacement therapy are excluded. Patients will be
recruited from our outpatient clinics.
At the first visit, patients who met inclusion criteria will be prescribed
160mg/day valsartan for 8 weeks. Other ACEi or ARB will be discontinued.
Diuretics are prescribed in order to maintain normovolumia, which is evidenced
by extracellular volume measurements. Furthermore, they are on standard
treatment, i.e. phosphate binders and vitamine D according to guidelines. Thus
the baseline dosage is 160mg/day of valsartan and the other dosages applied in
this study are 320mg/day and 640 mg/day. The first set of measurements will be
done while patients are on 160mg/day. Then patients will be randomly allocated
to receive either 640 mg/day valsartan or 320 mg/day valsartan for the
following 8 weeks. After 8 weeks the measurements will be repeated and the
groups will be switched to 320mg/day and 640mg/day respectively. At the end the
final set of measurements will be done (see study protocol page 19 for the
flowchart).
Other medication will not be changed during the entire study. In addition to
MSNA measurement, blood pressure, heart rate, bromide distribution, PRA and
other standard laboratory tests will be done on each occasion.
Intervention
Participants of this study receive 160mg/day valsartan for 8 weeks. After the
first 8 weeks the first MSNA measurement will be done. Then patients will be
randomized in group 320mg/day and group 640mg/day.
They will recieve 320mg/day or 640mg/day valsartan for 8 weeks. At the end of
this period the second MSNA measurement will be done by participants of both
groups.
Then the groups will be switched. The participants will receive 640mg/day or
320mg/day valsartan for 8 weeks. At the end the third MSNA measurement will be
done.
Study burden and risks
The risks associated with participation in this study are very limited.
Microneurography: there are no risks associated with this procedure. Usually,
nerve recordings cause minimal discomfort and negligible, transient
after-effects, when studies are done by an experienced technician.
Application of valsartan:
It has been shown that side effects induced by valsartan is relatively same as
placebo. Therefore the side effects could be considered negligible. A recent
study indicated that dosages of 1.5 to 5 times higher than presently maximum
licensed dosage in CKD patients are safe. See protocol "Summary of findings
from non-clinical studies and clinical studies" page 11 for references.
Heidelberglaan 100
3584 CX Utrecht
Nederland
Heidelberglaan 100
3584 CX Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
Patients with stable chronic kidney disease and hypertension: i.e. using antihypertensive drugs and/or blood pressure >145/90mmHg when off medication.
Exclusion criteria
Patients with diabetes mellitus and patients on renal replacement therapy are excluded. In addition, patients with severe liver insufficiency, biliary cirrhosis and cholestasis, pregnant patients and patients in lactation are excluded as Valsartan is contra-indicated for these patients.
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 |
|---|---|
| EudraCT | EUCTR2007-003181-18-NL |
| CCMO | NL18192.041.07 |