Preserving Kidney Function in Children With Chronic Kidney Disease

Pediatric Kidney Disease Clinical Trial

— PRESERVE  

Official title:

Preserving Kidney Function in Children With Chronic Kidney Disease (PRESERVE)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05169411
• Other study ID #: 21-018814
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 22, 2023
• Est. completion date: June 2024

Study information

• Verified date: November 2023
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pediatric chronic kidney disease (CKD) results from health conditions that reduce kidney function for >3 months. It can progress to end-stage kidney disease (ESKD), which requires dialysis or kidney transplant. In adults, CKD is common and caused mainly by hypertension and diabetes. CKD in childhood is rare and caused primarily by congenital anomalies of the genitourinary system and immune-mediated disorders. The best estimate of pediatric CKD prevalence is <1/15,000 pediatric population. Hypertension occurs in 50% of affected children and is a major risk factor for decline in kidney function. Several clinical practice guidelines have offered recommendations for blood pressure (BP) management in pediatric CKD; however, clinical trial and large-scale observational data are limited, leading to a weak evidence base and substantial practice variation. The purpose of PRESERVE is to provide new knowledge to inform shared decision-making regarding BP management for pediatric CKD. We will leverage the Patient-Centered Outcomes Research network (PCORnet®) infrastructure to conduct large-scale observational studies that will address BP management knowledge gaps for pediatric CKD and sub-groups for whom antihypertensive treatment and outcome associations may be different (e.g., cause of kidney disease and proteinuria).

The project's specific aims are:

Aim 1-Enhance the PCORnet Common Data Model (CDM) for pediatric and rare kidney disease research. We will expand and improve the PCORnet CDM with new pediatric- and kidney-specific variables, study-specific data quality optimization, and linkage with the chronic kidney disease in children (CKiD) cohort study and the US Renal Data System (USRDS). CKiD directly measures kidney function [ie, glomerular filtration rate (GFR)] and includes Ambulatory Blood Pressure Monitoring (ABPM). The USRDS provides complete capture of renal replacement therapy [(RRT) dialysis and transplant], two components of the primary clinical outcome.

Aim 2-Describe and examine the effectiveness of consistent BP and urine protein monitoring for preserving kidney function. We will describe the consistency of BP and urine protein monitoring and will contrast clinic BP assessments with ABPM. In longitudinal analyses, we will evaluate the effects of consistent monitoring of BP and urine protein on kidney function decline.

Aim 3-Compare the effectiveness of BP medication strategies for preserving kidney function. We will compare the effects of (1) BP levels when treatment was started, (2) choice of first-line therapies, and (3) ongoing BP control on kidney function decline. We will also assess adverse events related to hypertension management.

Aim 4-Assess patients' lived experiences related to BP management. We will field a survey that examines patient-centered outcomes by level of BP control and medication management approaches. This Aim will provide information on experiences with BP management from the perspectives of patients, parents, and clinicians that will complement the clinical outcomes studied in Aims 2 and 3.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 11084
• Est. completion date: June 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

Inclusion Criteria:

• Include: patient has an outpatient, ED, or inpatient visit with a physician

• Include: 1 or more eGFR values 30-89 mL/min/1.73m2 using the CKiD U25 formula

• Include: 2 or more eGFR values 30-89 mL/min/1.73m2 on different days using the CKiD U25 formula

• Include: 2 eGFR values in the range 30-89 mL/min/1.73m2 using the CKiD U25 formula greater than or equal to 90 days apart.

Exclusion Criteria:

• Exclude: eGFR value >=90 ml/min using the CKiD U25 formula between the two qualifying eGFRs in mild-moderate range

• Exclude if: Age <1 and >=18 years on CED (see below for definition of CED)

• Exclude if: no nephrologist visit at any time during the study period

• Exclude: if chronic dialysis on or before CED

• Exclude: if kidney transplant on or before CED

Related Conditions & MeSH terms

• Chronic Kidney Disease Stage 2
• Chronic Kidney Disease Stage 3
• Kidney Diseases
• Pediatric Kidney Disease
• Renal Insufficiency, Chronic

Intervention

Diagnostic Test:
• Blood pressure
The first anti-hypertensive prescribed will be categorized as ACEi, ARB, thiazide diuretic, loop diuretic, beta-blocker, calcium channel blocker, other, and none; secondary analyses will combine ACEi and ARB into a single RAAS blocker category. We will conduct additional secondary analyses for specific medications with sufficient sample sizes.
• Urine protein
Evaluating urine protein for children with CKD and hypertension is another guideline recommendation, but the frequency, type of assessment (qualitative or quantitative urine protein), and utility for patients without hypertension are unclear. We will determine whether urine protein is evaluated at each encounter and create a dichotomous indicator.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (19)

Lead Sponsor

Collaborator

Children's Hospital of Philadelphia

Alfred I. duPont Hospital for Children, Ann & Robert H Lurie Children's Hospital of Chicago, Children's Hospital Medical Center, Cincinnati, Duke University, Indiana University, Johns Hopkins University, Medical College of Wisconsin, Nationwide Children's Hospital, Patient-Centered Outcomes Research Institute, Seattle Children's Hospital, Stanford University, University of Colorado, Denver, University of Florida, University of Iowa, University of Miami, University of Michigan, University of North Carolina, Chapel Hill, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decline in estimated glomerular filtration rate (eGFR)	Time from cohort entrance (defined as day when first estimated glomerular filtration rate will be measured by the following criteria: (1) >50% decline in eGFR, as measured by the U25 formula; (2) eGFR <=15 ml/min as measured by the U25 formula); (3) initiation of chronic dialysis; or (4) kidney transplant.; U25 formula: https://doi.org/10.1016/j.kint.2020.10.047	up to 18 months