Severe Sepsis in Children - IMPRESS-C

NCT ID: NCT02598674

Last Updated: 2020-12-09

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-31
• Study Completion Date: 2021-09-30

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.

Detailed Description

This will be a two-arm cross-sectional control-cohort outpatient evaluation. Subjects with sAKI and control subjects (age and gender matched) will be recruited from neurology service. Subjects will be asked to come in to the Clinical Research Center for 24-hour monitoring and participate in the outpatient study where urinary and serum studies to measure glomerular filtration rate, renal plasma flow followed by blood pressure monitoring, peripheral arterial and applanation tonometry.

Conditions

Acute Kidney Injury; Chronic Kidney Disease; Hypertension

Keywords

acute kidney injury

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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).

Iodohippurate

Intervention Type: DRUG

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

24 hour ambulatory Blood Pressure

Intervention Type: 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.

Peripheral Arterial Tonometry

Intervention Type: PROCEDURE

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

Pulse Wave Velocity

Intervention Type: 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.

Gadolinium

Intervention Type: DRUG

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

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).

24 hour ambulatory Blood Pressure

Intervention Type: 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.

Peripheral Arterial Tonometry

Intervention Type: PROCEDURE

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

Pulse Wave Velocity

Intervention Type: 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.

Gadolinium

Intervention Type: DRUG

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

Interventions

Iodohippurate

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

Intervention Type: DRUG

24 hour ambulatory Blood Pressure

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.

Intervention Type: PROCEDURE

Peripheral Arterial Tonometry

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

Intervention Type: PROCEDURE

Pulse Wave Velocity

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.

Intervention Type: PROCEDURE

Gadolinium

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

Intervention Type: DRUG

Other Intervention Names

RPF filtration; Dotarem Gadolinium (GD); Glomerular Function Rate (GFR) filtration

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Society of Nephrology

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie-Carmelle Elie, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Health

Gainesville, Florida, United States

Countries

United States

Other Identifiers

IRB201500264

Identifier Type: -

Identifier Source: org_study_id