Primary objective: To compare the anti-hypertensive response to dietary salt restriction with the anti-hypertensive response to the diuretics hydrochlorothiazide/amiloride in patients with CKD stages 3 or 4. Secondary objectives: * To analyze the…
ID
Source
Brief title
Condition
- Nephropathies
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ambulatory (24-hour) blood pressure measurement (ABPM).
Secondary outcome
- Number of AEs and SAEs.
- Effects of the interventions on blood and urinary parameters (routine
measurements, systemic RAS, intrarenal RAS, kidney injury markers, urinary
exosomes)
Background summary
Patients with chronic kidney disease (CKD) are exquisitely salt-sensitive.
Salt-sensitivity in CKD is linked to hypertension and cardiovascular outcomes.
Dietary salt restriction is an accepted intervention for salt-sensitivity in
CKD. Another strategy, however, could be to block sodium uptake by the kidney
pharmacologically by diuretics. Especially diuretics acting on the distal
tubule may be effective, because this appears to be the site of increased
sodium reabsorption in CKD. It is currently unknown how these two strategies,
diet or diuretics, relate. We hypothesize that diuretics are non-inferior to
diet.
Study objective
Primary objective:
To compare the anti-hypertensive response to dietary salt restriction with the
anti-hypertensive response to the diuretics hydrochlorothiazide/amiloride in
patients with CKD stages 3 or 4.
Secondary objectives:
* To analyze the response in kidney parameters, the systemic and intra-renal
renin-angiotensin system to the two interventions.
* To compare the side-effects of the two interventions.
Study design
Randomized open crossover trial.
Intervention
Patients will be randomized to receive amiloride/hydrochlorothiazide (tablet
5/50mg, once daily) or a dietary sodium restriction (60 mmol/day). Patients
with a low dietary sodium intake prior to start of the study (24-hour urinary
sodium excretion < 80 mmol/l) will receive 4000 mg sodium chloride daily (4 x
capsule 500 mg, twice daily) during the study (except for the period of the
low-sodium diet). The study will last 8 weeks (2 week run-in period, 2 x 2-week
treatment period + 2-week wash-out period).
Study burden and risks
The study will require: 5 study visits, 1 dietician visit, 5 venapunctures, 4
24-hour urine collections, and 4 ABPMs.
The main risks of this study are uncontrolled blood pressure and side-effects
of the diuretics. However, because of the daily home monitoring of blood
pressure, availability of escape medication, and the short treatment periods (2
weeks), we believe these potential risks are well-controlled for.
The benefit for individual participants may be that, after the study, the best
intervention for salt-sensitivity for this individual will be known and this
treatment may be continued. Another benefit may be that, because of the
frequent visits to the dietician, patients will have elaborate knowledge on
sodium content of their food and ways to adhere to a low-sodium diet.
Dr. Molewaterplein 50
Rotterdam 3015GE
NL
Dr. Molewaterplein 50
Rotterdam 3015GE
NL
Listed location countries
Age
Inclusion criteria
- Age > 18 years.
- Chronic kidney disease stage 3 or 4 (MDRD-GFR 15-60 ml/min)
- Use of any anti-hypertensive drugs
- No anti-hypertensive drugs but an average office systolic blood pressure > 140 mmHg (as measured by datascope)
Exclusion criteria
- Salt-wasting chronic kidney disease
- Nephrotic syndrome
- Pregnant or breastfeeding women
- Life expectancy < 6 months
- Severe heart failure (NYHA III or IV) or liver cirrhosis with ascites and the inability to withdraw diuretics
- Rapidly declining kidney function with high likelihood of dialysis or kidney transplantation in the coming 4 months
- Kidney transplant recipients
- Use of immunosuppressive drugs
- Use of non-steroidal anti-inflammatory drugs
- Previous intolerance or allergy to hydrochlorothiazide or amiloride
- Serum sodium < 135 mmol/l
- Serum potassium < 3.5 mmol/l or > 5.0 mmol/l
- Inability to adhere to the 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
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003637-96-NL |
| CCMO | NL54748.078.15 |