Severe Sepsis in Children - IMPRESS-C

NCT02598674 | Withdrawn

• 1 other identifier: IRB201500264
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is the most common cause of childhood death worldwide. Millions of children survive, but are left with impaired health. Sepsis-related Acute Kidney Injury (sAKI) is increasingly recognized as a significant factor associated with long-term mortality among different patient populations. Renal dysfunction and subsequent chronic kidney disease is implicated in the development of hypertension and cardiovascular disease. The investigators overall hypothesis is that, in the pediatric population, sepsis-related AKI will have unrecognized, long-term consequences with regard to kidney function, endothelial function, blood pressure control, and overall health.

Conditions

Acute Kidney Injury; Chronic Kidney Disease; Hypertension

Keywords

acute kidney injury

Outcome Measures

Primary Outcomes (4)

• Glomerular Function Rate (GFR) filtration

  Magnevist Gadolinium (GD)-diethylene-triamine-pentaacetic acid-bis-oleate (0.07 to 0.14 mL/kg) will be used to determine GFR.

  Day 2

• Renal plasma flow (RPF) filtration

  An injection of non-radioactive iodohippurate (0.07 mL/kg) will be administered to determine renal plasma flow (RPF) filtration.

  Day 2

• Proteinuria will be measured in the urine

  Proteinuria may be a sign of renal (kidney) damage. Since serum proteins are readily reabsorbed from urine, the presence of excess protein indicates either an insufficiency of absorption or impaired filtration. People with diabetes may have damaged nephrons and develop proteinuria.

  Day 2

• Cystatin C will be measured in the blood

  Cystatin C can be measured in a random sample of serum (the fluid in blood from which the red blood cells and clotting factors have been removed) using immunoassays such as nephelometry or particle-enhanced turbidimetry.

  Day 2

Secondary Outcomes (3)

• 24 hour ambulatory Blood Pressure

  24 hours

• Peripheral Arterial Tonometry

  24 hours

• Pulse wave velocity

  24 hours

Study Arms (2)

Sepsis with Severe AKI

This group will have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI) which lead to classification of "injury" or "failure". The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).

Drug: Iodohippurate; Procedure: 24 hour ambulatory Blood Pressure; Procedure: Peripheral Arterial Tonometry; Procedure: Pulse Wave Velocity; Drug: Gadolinium

Control

This group will not have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI). The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).

Procedure: 24 hour ambulatory Blood Pressure; Procedure: Peripheral Arterial Tonometry; Procedure: Pulse Wave Velocity; Drug: Gadolinium

Interventions

Iodohippurate DRUG

An injection of non-radioactive iodohippurate (0.07 mL/kg) will be administered to determine renal plasma flow (RPF)

Also known as: RPF filtration

Sepsis with Severe AKI

24 hour ambulatory Blood Pressure PROCEDURE

Ambulatory blood pressure (BP) monitoring will be performed using a commercially available device (TIBA Ambulo 2400) for 24 hours with measurements every 30 minutes while awake and every hour during sleep.

Control; Sepsis with Severe AKI

Peripheral Arterial Tonometry PROCEDURE

The peripheral arterial tonometry (PAT) device measures changes in the cutaneous circulation that correlate with flow-mediated dilatation.

Control; Sepsis with Severe AKI

Pulse Wave Velocity PROCEDURE

Carotid-femoral and carotid-radial pulse wave velocities (PWV), validated markers of individual cardiovascular risk, will be determined by applanation tonometry using SphygmoCorVx technology (AtCor Medical). PWV is an index of the overall stiffness of a vascular segment between measurement sites 59. Thus, while carotid-femoral PWV is an index of the overall stiffness of proximal (central) arteries, the overall stiffness of peripheral arteries contributes relatively more to carotid-radial PWV.

Control; Sepsis with Severe AKI

Gadolinium DRUG

Dotarem Gadolinium (GD)- Gadoterate Meglumine (0.07 to 0.14 mL/kg) will be used to determine GFR.

Also known as: Dotarem Gadolinium (GD), Glomerular Function Rate (GFR) filtration

Control; Sepsis with Severe AKI

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Contact and enroll subjects with severe sepsis related AKI subjects without sepsis related AKI and a sample of age and sex-matched healthy controls.

You may qualify if:

• For all patients:
• Ability to assent (age 7-17 at time of participation in the study)
• If taking antihypertensive medication, prescribing practitioner's written approval to participate
• For sAKI patients:
• Hospitalization with a diagnosis of sepsis from 1998-2014
• Severe AKI as defined by the pEDRIFLE criteria during incident sepsis admission
• Participation in cognitive survey study with completion of the PedsQL survey
• For healthy control patients:
• Patients from the neurology service undergoing MRI with gadolinium as a part of their clinical care

You may not qualify if:

• For all patients:
• Known pre-existing CKD as defined by history of kidney transplant or long-term dialysis
• Age greater than 17 years at the time of incident sepsis admission
• AKI from primary kidney disease including acute glomerulonephritis and obstructive uropathy
• Pregnancy at the time of enrollment
• Known or suspected allergy to gadolinium based contrast
• Known or suspected allergy to iodohippurate will be excluded from RPF measurement with iodohippurate
• Heart failure or condition whereby the administration of 0.9% normal saline would be contraindicated
• If taking antihypertensive medication, lack of prescribing practitioner's written approval to participate
• For healthy control patients:
• Chronic kidney disease
• History of acute kidney injury or GFR \<100 History of chronic illnesses deemed to predispose to renal or cardiovascular dysfunction or abnormalities Suspicion of infection
• Neuro-vascular history such as encephalitis, meningitis, vascular anomalies of the brain or spinal cord or cerebrovascular infarct or ischemia will be excluded .
• No indication for gadolinium administration for MRI

Sponsors & Collaborators

• University of Florida: lead
• American Society of Nephrology: collaborator

Study Sites (1)

UF Health

Gainesville, Florida, 32608, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum and urine

MeSH Terms

Conditions

Acute Kidney Injury; Renal Insufficiency, Chronic; Hypertension

Interventions

Iodohippuric Acid; Gadolinium; Glomerular Filtration Rate; Filtration

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hippurates; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Keto Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Metals; Kidney Function Tests; Diagnostic Techniques, Urological; Diagnostic Techniques and Procedures; Diagnosis; Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Chemistry Techniques, Analytical; Investigative Techniques; Physical Phenomena; Chemical Phenomena

Study Officials

• Marie-Carmelle Elie, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2015
• First Posted: November 6, 2015
• Study Start: October 1, 2019
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: December 9, 2020

Record last verified: 2020-12

Locations

US (1)