Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies
Primary Purpose
Uric Acid Nephropathy
Status
Recruiting
Phase
Phase 4
Locations
Argentina
Study Type
Interventional
Intervention
Losartan Potassium
Sponsored by
About this trial
This is an interventional treatment trial for Uric Acid Nephropathy
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.
Sites / Locations
- HGNPERecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Enalapril
Losartan
Arm Description
Children with proteinuric nephropathies will receive enalapril prior or after a losartan period, according to randomization sequence. Enalapril will be given at a dose between 0.1 to 0.4 mg/kg/day (according to the dose that they usually receive), once a day.
Children with proteinuric nephropathies will receive losartan prior or after a enalapril period, according to randomization sequence. Losartan will be given at a dose 5 times the dose of enalapril that they usually receive, (with a maximum dose of 1.4 mg/kg/day), once a day.
Outcomes
Primary Outcome Measures
Serum uric acid levels after losartan treatment
Patiens will receive a losartan regime after serum uric acid levels will be assessed
Secondary Outcome Measures
Urinary uric acid levels after losartan treatment
Patiens will receive a losartan regime after urinary uric acid levels will be assessed
Full Information
NCT ID
NCT05402397
First Posted
May 30, 2022
Last Updated
November 24, 2022
Sponsor
Hospital General de Niños Pedro de Elizalde
1. Study Identification
Unique Protocol Identification Number
NCT05402397
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital General de Niños Pedro de Elizalde
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uric Acid Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
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).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Enalapril
Arm Type
Active Comparator
Arm Description
Children with proteinuric nephropathies will receive enalapril prior or after a losartan period, according to randomization sequence.
Enalapril will be given at a dose between 0.1 to 0.4 mg/kg/day (according to the dose that they usually receive), once a day.
Arm Title
Losartan
Arm Type
Experimental
Arm Description
Children with proteinuric nephropathies will receive losartan prior or after a enalapril period, according to randomization sequence.
Losartan will be given at a dose 5 times the dose of enalapril that they usually receive, (with a maximum dose of 1.4 mg/kg/day), once a day.
Intervention Type
Drug
Intervention Name(s)
Losartan Potassium
Intervention Description
Patients will receive losartan potassium for 30 days.
Primary Outcome Measure Information:
Title
Serum uric acid levels after losartan treatment
Description
Patiens will receive a losartan regime after serum uric acid levels will be assessed
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Urinary uric acid levels after losartan treatment
Description
Patiens will receive a losartan regime after urinary uric acid levels will be assessed
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alejandro Balestracci, MD, Ph.D.
Phone
54943632100
Ext
3038
Email
abalestracci@yahoo.com.ar
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Beaudoin, MD
Phone
54943632100
Ext
3038
Email
beaudoinmarialaura@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alejandro Balestracci, MD, Ph. D.
Organizational Affiliation
Hospital General de Niños Pedro de Elizalde
Official's Role
Principal Investigator
Facility Information:
Facility Name
HGNPE
City
Caba
ZIP/Postal Code
1417
Country
Argentina
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alejandro Balestracci, MD, PhD
Phone
541140345402
Email
abalestracci@yahoo.com.ar
First Name & Middle Initial & Last Name & Degree
Laura Beaudoin, MD
Phone
541121593149
Email
beaudoinmarialaura@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The authors will share the generated data with qualified external researchers during the next 5 years after article publication. All data provided will be anonymized to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.
IPD Sharing Time Frame
During the next 5 years after article publication.
IPD Sharing Access Criteria
Qualified external researchers
Citations:
PubMed Identifier
32872730
Citation
Park JH, Jo YI, Lee JH. Renal effects of uric acid: hyperuricemia and hypouricemia. Korean J Intern Med. 2020 Nov;35(6):1291-1304. doi: 10.3904/kjim.2020.410. Epub 2020 Sep 9.
Results Reference
result
PubMed Identifier
18335252
Citation
Wuhl E, Schaefer F. Therapeutic strategies to slow chronic kidney disease progression. Pediatr Nephrol. 2008 May;23(5):705-16. doi: 10.1007/s00467-008-0789-y. Epub 2008 Mar 12.
Results Reference
result
PubMed Identifier
29931555
Citation
Weaver DJ Jr. Uric acid and progression of chronic kidney disease. Pediatr Nephrol. 2019 May;34(5):801-809. doi: 10.1007/s00467-018-3979-2. Epub 2018 Jun 21.
Results Reference
result
PubMed Identifier
31390929
Citation
Sutton Burke EM, Kelly TC, Shoales LA, Nagel AK. Angiotensin Receptor Blockers Effect on Serum Uric Acid-A Class Effect? J Pharm Pract. 2020 Dec;33(6):874-881. doi: 10.1177/0897190019866315. Epub 2019 Aug 7.
Results Reference
result
PubMed Identifier
33881639
Citation
Bryant CE, Rajai A, Webb NJA, Hogg RJ. Effects of losartan and enalapril on serum uric acid and GFR in children with proteinuria. Pediatr Nephrol. 2021 Oct;36(10):3211-3219. doi: 10.1007/s00467-021-05045-4. Epub 2021 Apr 21.
Results Reference
result
PubMed Identifier
18670416
Citation
Hamada T, Ichida K, Hosoyamada M, Mizuta E, Yanagihara K, Sonoyama K, Sugihara S, Igawa O, Hosoya T, Ohtahara A, Shigamasa C, Yamamoto Y, Ninomiya H, Hisatome I. Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients. Am J Hypertens. 2008 Oct;21(10):1157-62. doi: 10.1038/ajh.2008.245. Epub 2008 Jul 31.
Results Reference
result
PubMed Identifier
31192008
Citation
Kubota M. Hyperuricemia in Children and Adolescents: Present Knowledge and Future Directions. J Nutr Metab. 2019 May 2;2019:3480718. doi: 10.1155/2019/3480718. eCollection 2019.
Results Reference
result
PubMed Identifier
16281062
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.
Results Reference
result
PubMed Identifier
11593107
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.
Results Reference
result
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Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies
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