Renin Angiotensin Aldosterone System In Septic Kids

Sepsis Clinical Trial

— RISK  

Official title:

Early Identification of Sepsis-associated Acute Kidney Injury Using Ultrasonography Measurements and Renin and Angiotensin Levels in Children and Adults.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06295393
• Other study ID #: 20-0229-CCMC
• Status: Recruiting
• Start date: January 24, 2024
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: Northwell Health
• Contact: Grace Fisler, MD
• Phone: 203-671-0654
• Email: gfisler[@]northwell.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Prospective observational cohort study; pediatric sepsis vs. healthy pediatric subjects and pediatric sepsis with acute kidney injury (AKI) vs without AKI.

Blood samples and renal ultrasound will be collected on sequential days for septic subject and one time for the healthy patients.

Enzyme-linked immunosorbent assays (ELISA) with be run on serum plasma to compare the renin-angiotensin-aldosterone system (RAAS) between groups.

Description:

Prospective observational cohort study; pediatric sepsis vs. healthy pediatric subjects and pediatric sepsis with AKI vs without AKI.

Powered to collect 74 patients total (37 sepsis,37 healthy) with enrollment ratio 1:1 and expected different of 50% in renin levels, this provides 80% power at an alpha of 0.05.

Sepsis identified as pediatric Sequential Organ Failure Assessment (pSOFA) >/= 2 + infection and/or Phoenix sepsis criteria.

Collecting blood samples on subsequent days of hospitalization. For healthy patients, a one-time blood draw will be obtained .

Renal ultrasound will be performed on day 1, 2 and 3 of hospitalization.

Blood will be collected and plasma stored at -80 degrees Celsius.

Plasma thawed in batches and ELISAs for RAAS components.

Demographic data will be collected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 18 Years

Eligibility

Inclusion Criteria:

• pediatric patients age 1 days - 18 years old with sepsis or age 1 day - 18 years and healthy.

Exclusion Criteria:

• -pre-existing end stage renal disease (ESRD), chronic renal failure (CRF), home use of angiotensin converting enzyme inhibitor(ACE) or angiotensin receptor blocker(ARB) medications, pre-existing congestive heart failure (CHF), and unrepaired congenital heart disease

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Kidney Injury (Nontraumatic)
• Acute Kidney Injury Due to Sepsis
• Sepsis
• Toxemia
• Wounds and Injuries

Locations

Country	Name	City	State
United States	Cohen Children's Medical Center	New Hyde Park	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

References & Publications (9)

Basu RK, Kaddourah A, Goldstein SL; AWARE Study Investigators. Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study. Lancet Child Adolesc Health. 2018 Feb;2(2):112-120. doi: 10.1016/S2352-4642(17)30181-5. — View Citation

Deja A, Skrzypczyk P, Nowak M, Wronska M, Szyszka M, Ofiara A, Lesiak-Kosmatka J, Stelmaszczyk-Emmel A, Panczyk-Tomaszewska M. Evaluation of Active Renin Concentration in A Cohort of Adolescents with Primary Hypertension. Int J Environ Res Public Health. 2022 May 13;19(10):5960. doi: 10.3390/ijerph19105960. — View Citation

Goswami E, Ogden RK, Bennett WE, Goldstein SL, Hackbarth R, Somers MJG, Yonekawa K, Misurac J. Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children. Am J Health Syst Pharm. 2019 Oct 30;76(22):1869-1874. doi: 10.1093/ajhp/zxz203. — View Citation

Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001. Epub 2017 Jun 21. No abstract available. Erratum In: Kidney Int Suppl (2011). 2017 Dec;7(3):e1. — View Citation

Matics TJ, Sanchez-Pinto LN. Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children. JAMA Pediatr. 2017 Oct 2;171(10):e172352. doi: 10.1001/jamapediatrics.2017.2352. Epub 2017 Oct 2. — View Citation

Menon K, Schlapbach LJ, Akech S, Argent A, Biban P, Carrol ED, Chiotos K, Jobayer Chisti M, Evans IVR, Inwald DP, Ishimine P, Kissoon N, Lodha R, Nadel S, Oliveira CF, Peters M, Sadeghirad B, Scott HF, de Souza DC, Tissieres P, Watson RS, Wiens MO, Wynn JL, Zimmerman JJ, Sorce LR; Pediatric Sepsis Definition Taskforce of the Society of Critical Care Medicine. Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce. Crit Care Med. 2022 Jan 1;50(1):21-36. doi: 10.1097/CCM.0000000000005294. — View Citation

Sanchez-Pinto LN, Bennett TD, DeWitt PE, Russell S, Rebull MN, Martin B, Akech S, Albers DJ, Alpern ER, Balamuth F, Bembea M, Chisti MJ, Evans I, Horvat CM, Jaramillo-Bustamante JC, Kissoon N, Menon K, Scott HF, Weiss SL, Wiens MO, Zimmerman JJ, Argent AC, Sorce LR, Schlapbach LJ, Watson RS; Society of Critical Care Medicine Pediatric Sepsis Definition Task Force; Biban P, Carrol E, Chiotos K, Flauzino De Oliveira C, Hall MW, Inwald D, Ishimine P, Levin M, Lodha R, Nadel S, Nakagawa S, Peters MJ, Randolph AG, Ranjit S, Souza DC, Tissieres P, Wynn JL. Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock. JAMA. 2024 Jan 21. doi: 10.1001/jama.2024.0196. Online ahead of print. — View Citation

Stanski NL, Pode Shakked N, Zhang B, Cvijanovich NZ, Fitzgerald JC, Jain PN, Schwarz AJ, Nowak J, Weiss SL, Allen GL, Thomas NJ, Haileselassie B, Goldstein SL. Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock. Pediatr Nephrol. 2023 Sep;38(9):3099-3108. doi: 10.1007/s00467-023-05930-0. Epub 2023 Mar 20. — View Citation

Zhi HJ, Zhao J, Nie S, Ma YJ, Cui XY, Zhang M, Li Y. Semiquantitative Power Doppler Ultrasound Score to Predict Acute Kidney Injury in Patients With Sepsis or Cardiac Failure: A Prospective Observational Study. J Intensive Care Med. 2021 Jan;36(1):115-122. doi: 10.1177/0885066619887333. Epub 2019 Nov 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in serum renin in sepsis	Comparison between healthy and septic subjects serum renin levels	For sepsis cohort point 1 collection within the first 48 hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94 hours. For the healthy cohort blood drawn at a single time point up to 24 hours
Secondary	Aberrations in the renin angiotensin aldosterone system (RAAS) in sepsis associated acute kidney injury	Comparison of RAAS components between sepsis with and without AKI	For sepsis cohort point 1 collection within the first 48 hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94 hours.
Secondary	Septic induced kidney injury will be associated with alterations in renal blood flow	Ultrasound will measure blood flow to kidneys during sepsis and compare with serum levels of RAAS	For sepsis cohort point 1 collection within the first 48 hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94 hours.
Secondary	Aberrations in the renin angiotensin aldosterone system (RAAS) in sepsis versus healthy patients	Comparison of RAAS components between sepsis and healthy	For sepsis cohort point 1 collection within the first 48hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94hours. For the healthy cohort blood drawn at a single time point.
Secondary	Changes in the components of the RAAS over the first three days in sepsis	Measuring components of RAAS over three days and comparing trend	For sepsis cohort point 1 collection within the first 48hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94hours.
Secondary	Changes in renal blood flow on Ultrasound in Sepsis	Measuring renal blood flow trend over first three days of sepsis	For sepsis cohort point 1 collection within the first 48 hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94 hours.
Secondary	Renal blood flow and RAAS in sepsis	Comparison between blood flow by renal ultrasound and components of RAAS	For sepsis cohort point 1 collection within the first 48 hours from of meeting sepsis criteria, point 2: 48-72 hours and point 3: 72-94hours.