Clinical trial NCT05402397: Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies
Official title: Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies: a Cross-over Randomized Clinical Trail
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Uric Acid Nephropathy
Lead sponsor: Hospital General de Niños Pedro de Elizalde
Sponsor class: OTHER
First posted: 2022-06-02
Enrollment: 40
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients already treated with enalapril will be randomized to receive losartan or enalapril in a cross-over designed study. Those who recruit the inclusion criteria will receive enalapril and/or losartan during a one month period, followed by a 15 days of wash out (under enalapril treatment). On day 46, the second period of 30 days of treatment starts (enalapril or losartan, whichever was not received initially).
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the serum uric-acid lowering effect of losartan in children with proteinuric nephropathies. Patients already treated with enalapril will be randomized to receive losartan and/or enalapril in a cross-over designed study. Those who recruit the inclusion criteria will receive enalapril and/or losartan during a one month period, followed by a 15 days of wash out (under enalapril treatment). On day 46, the second period of 30 days of treatment start (enalapril or losartan, whichever was not received initially). Before randomization, a baseline 24 hours urine and a fasting blood sample will be obtained to assess uric acid excretion and serum uric acid values along with renal function and electrolyte levels. Then, similar determinations will be performed at days 30, 46 and 76.

Detailed description: The working hypothesis is that the administration to losartan reduces significantly the serum uric acid levels in normotensive children with proteinuric nephropathies. The study will consist in a single center cross-over randomized, open label, clinical trial.

Inclusion criteria will be:children with poteinuric nephropathies already treated with enalapril under our care, age between 3 and 12 years and normal blood pressure.

Subjects will be selected by simple probability sampling and after the signature of the assent/informed consent, they will be randomized (blocks of 4 patients, treatment sequence 2:2) to receive a two phases regime of drugs: 1) arm enalapril-losartan, or 2) arm losartan-enalapril. Between phases there will be a 14 days wash out period (during this time patients will continue receiving enalapril, as this drug does not have effect on uric acid metabolism). The dose of enalapril will be that they usually receive, while the dose of losartan will be 5 times the those of enalapril that they usually receive.

Visit Schedule: day 1 (randomization) and 30 for the first drug; 15 days wash out period, day 46 and 76 for the second drug. In each visit a physical examination and blood pressure monitor will be performed, along with the following laboratory parameters: urea, creatinine, electrolytes, uric acid, glycemia, triglycerides, cholesterol and lipopolysaccharides. Simultaneously, in a spot urine morning sample will be determined the levels of uric acid, creatinine, proteinuria y albuminuria.

Eligibility criteria: Inclusion Criteria:

* Children with poteinuric nephropathies already treated with enalapril under our care.
* Age between 3 and 12 years.
* Normal blood pressure.

Exclusion Criteria:

* Patients with high blood pressure.
* Post menarche female patients.
* Patients with hypouricemia (\< 2 mg/dL).
* Patients treated with diuretics.
* Patients with absolute or relative contraindications to receive RAAS antagonists (glomerular filtration \< 30 ml/min/1,73 m2, serum potassium \> 5,5 mEq/L).
* Patients with active rheumatic diseases.
* Patients treated with dual blockade of the RAAS (enalapril +losartan).
* Patients treated with calcineurin inhibitors.

Primary outcomes:
measure: Serum uric acid levels after losartan treatment
timeFrame: 30 days
Secondary outcomes:
measure: Urinary uric acid levels after losartan treatment
timeFrame: 30 days
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: HGNPE
Study officials:
affiliation: Hospital General de Niños Pedro de Elizalde
name: Alejandro Balestracci, MD, Ph. D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Dang A, Zhang Y, Liu G, Chen G, Song W, Wang B. Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population. J Hum Hypertens. 2006 Jan;20(1):45-50. doi: 10.1038/sj.jhh.1001941.
citation: Wurzner G, Gerster JC, Chiolero A, Maillard M, Fallab-Stubi CL, Brunner HR, Burnier M. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens. 2001 Oct;19(10):1855-60. doi: 10.1097/00004872-200110000-00021.