To compare the antiproteinuric effects of sacubitril/valsartan (ARNI) and valsartan (ARB).
ID
Source
Brief title
Condition
- Other condition
- Diabetic complications
- Nephropathies
Synonym
Health condition
hypertensie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our primary endpoint is change in 24-hour proteinuria, compared between
sacubitril/valsartan treatment and valsartan treatment.
Secondary outcome
Secondary endpoints include the effects on ambulatory blood pressure, eGFR,
number of AEs and SAEs, parameters of kidney damage,
renin-angiotensin-aldosterone system and natriuretic peptide system.
Background summary
Patients with chronic kidney disease (CKD) are at high risk of progression
towards end-stage renal disease and requirement of renal replacement therapy.
Current therapy is insufficient to prevent progression of CKD. Angiotensin
Receptor/Neprilysin Inhibitor (ARNI) is a novel therapy, currently registered
for the treatment of patients with heart failure, in which studies showed a
great reduction in mortality and hospitalization. Interestingly, ARNI also
reduced proteinuria in patients with CKD and hypertension. Moreover, in rats
with diabetic, hypertensive nephropathy, we observed greater beneficial effects
on proteinuria and glomerulosclerosis after ARNI, when compared to single AR
blockade (ARB), despite a similar effect on blood pressure. This suggests that
ARNI may be a very effective drug in patients with CKD, hypertension and
diabetes, but this has not yet been tested. Therefore, our aim is to compare
the renoprotective effects of ARNI and ARB in patients with CKD, hypertension
and diabetes.
Study objective
To compare the antiproteinuric effects of sacubitril/valsartan (ARNI) and
valsartan (ARB).
Study design
Single-center, randomized, open label, cross-over trial.
Intervention
Patients will be randomized to receive sacubitril/valsartan (initial dosage 97
mg / 103 mg, once daily; final dosage 97 mg / 103 mg twice daily) or valsartan
(initial dosage 160 mg, once daily; final dosage 160 mg twice daily). Due to
higher biological availability, 160 mg valsartan is equipotent to 103 mg
valsartan in the combination drug. The study will last 14 weeks (2 week run-in
period in which current RAAS inhibition will be stopped, 2 x 5-week treatment
period + 2-week wash-out period).
Study burden and risks
The study will require: 7 study visits, 7 venapunctures, 4x 24-hour urine
collections, and 4 ambulatory blood pressure measurements.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
* Age > 18 years
* Chronic kidney disease stage 3 or 4 (eGFR 15-60 ml/min/1.73m2)
* Residual proteinuria during RAAS blockade (* 1 g/day)
* Diabetes mellitus type 2
* Hypertension (office systolic blood pressure > 140 mmHg OR use of any anti-hypertensive drug)
Exclusion criteria
* SBP >180 mmHg at screening
* Not possible to withdraw ACEi or ARB
* Known intolerance or contraindication for ARB
* History of angioedema
* Nephrotic syndrome
* Rapidly declining kidney function with high likelihood of dialysis or transplantation in the coming 4 months
* Use of immunosuppressive drugs
* Kidney transplant recipients
* Pregnant or breastfeeding women
* Life expectancy < 6 months
* Inability to adhere to study protocol (due to language, incapacitated subjects, subjects with intellectual disability)
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 | EUCTR2017-000213-23-NL |
| CCMO | NL60561.078.17 |