Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS

Sepsis Clinical Trial

Official title:

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care Subtitle. Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02276066
• Other study ID #: IRB201400795-N
• Secondary ID: P50GM111152-01
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2015
• Est. completion date: November 2022

Study information

• Verified date: December 2021
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study investigates the mechanism by which kidney dysfunction perpetuates inflammation, immunosuppression, and catabolism (PICS) in chronic critical illness. The investigators will test the hypothesis that persistent kidney dysfunction in sepsis associated by chronic critical illness contributes to decreased survival through the development of PICS. In chronic critical illness, the persistence of the inflammatory state may lead to capillary rarefication in the kidney causing accelerated chronic kidney disease. Progression of chronic kidney disease during chronic critical illness can drive PICS. Indeed, many of the features of chronic critical illness are consistent with the protein-energy malnutrition and muscle wasting associated with chronic kidney disease. Thus, the kidney can play a contributory role in chronic critical illness and PICS.

Description:

The main goal of this project is to measure kidney filtration function at day 14 or the day of discharge from hospital (whichever occurs first), in order to determine the presence and magnitude of persistent kidney dysfunction after sepsis episode and to longitudinally assess further decline of kidney function at one year follow-up. The measure of the glomerular filtration rate (GRF) in patients with chronic critical illness and controls (sepsis patients discharged from ICU before day 14) will be used to determine to what degree of kidney dysfunction contributes to decreased survival and increase in chronic kidney disease at year one after sepsis onset.

One and/or all of the three ways for GFR assessment will be used, both at approximately day 14 or approximately at the day of discharge from the ICU and at the one year follow up :

1. Determine clearance of Iohexol from blood after Iohexol injection and/or

2. Determine apperance of Iohexol in urine after Iohexol injection (this would be the same injection as in one, and would not require two injections) and/or

3. A timed urine collection to determine clearance of urea and creatinine and/or

4. Estimated GFR using calculations with serum creatinine and cystatin C,

This will provide an opportunity to validate the different measurements.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 86
• Est. completion date: November 2022
• Est. primary completion date: November 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Presence in the surgery or trauma ICU

• Age of =18 years

• Entrance into our sepsis protocol

• Ability to obtain informed consent.

Exclusion Criteria:

• Expected lifespan of the patient is less than 3 months due to severe pre-existing comorbidities (ex. recurrent, advanced or metastatic cancer)

• Severe traumatic brain injury (evidence of neurologic injury on CT scan and a GCS <8)

• Refractory shock (i.e., patients who die within 12 hours)

• Uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel)

• Patient or patient's family are not committed to aggressive management of the patient's condition and/or the patient has a DNR/DNI on file.

• Severe CHF (NY Heart Association Class IV)

• Child-Pugh C liver disease or pre-liver transplant.

• Known HIV infection with CD4 count <200 cells/mm3

• Organ transplant recipient on immunosuppressive agents

• Known pregnancy and mother's that are breastfeeding

• Prisoners

• Institutionalized patients

• Inability to obtain informed consent.

• Chemotherapy or radiotherapy within 30 days prior to sepsis.

• End stage renal disease on admission.

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Other:
• Iohexol
Both groups of sepsis participants will receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year.
• Urine Collection
Both groups of sepsis participants will have urine collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine and urea concentration.
• Blood samples
Both groups of sepsis participants will provide peripheral blood samples to the research staff. The samples will be sent to the laboratory for serum creatinine and cystatin C results.

Locations

Country	Name	City	State
United States	UF Health at Shands hospital	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve versus time curve (AUC) of Iohexol	The decline in iohexol glomerular filtration rate at day 14 and 1 year follow-up between chronic crucial illness and control groups.	0, 1, 2, 3, and 4 hours post-dose
Secondary	Serum Creatinine	The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.	Day 14
Secondary	Serum Creatinine	The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.	1 year
Secondary	Urine Urea Concentration	The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of urea concentration.	Day 14
Secondary	Urine Urea Concentration	The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of urea concentration.	1 year
Secondary	Urine Creatinine Ratio	The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine.	Day 14
Secondary	Urine Creatinine Ratio	The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine.	1 year