PICS: Subtitle Cardiac Dysfunction in Older Sepsis Survivors

Sepsis Clinical Trial

— PICS  

Official title:

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care Subtitle: Cardiac Dysfunction in Older Sepsis Survivors Subtitle: Development of a Designer Proline-Rich Antimicrobial Peptide Chaperone Protein Inhibitor (DPC) for Treating Sepsis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02276417
• Other study ID #: IRB201400611-N
• Secondary ID: P50GM111152-01OC
• Status: Active, not recruiting
• Start date: January 2015
• Est. completion date: July 24, 2025

Study information

• Verified date: December 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to define the natural history and causes of chronic critical illness (CCI) in surgical intensive care patients who have had sepsis. The investigator also wants to define the long-term physical and cognitive outcomes of this disease. The investigator will be looking at many clinical variables to try to define CCI.

Description:

This is a prospective, observational study aimed at identifying the frequency, natural history and long term outcomes of CCI and PICS in the survivors of surgical or trauma-associated sepsis. A major portion of the translational data to be obtained will be from urine and blood samples from septic patients identified in the surgery and trauma ICUs. The blood will be processed for genomic markers, inflammatory markers, immunosuppression markers, Myeloid Derived Suppressor Cells (MDSC) functions, and angiogenic factors. The urine will be processed for messenger RNA (mRNA) isolation and protein biomarkers. Bioimpedance analysis will performed to assess body composition. In order to assess the long term outcomes, the following Quality-of-life, functional and cognitive tests will be performed. Health-related quality of life questionnaire, EuroQol-5D, Mini Nutritional Assessment Form, the Hopkins Verbal Learning Test, Controlled Oral Word Association, Modified Mini-Mental Status Exam, Short PhysicalPerformance Battery, Hand Grip Strength Measurement and The Eastern Cooperative Oncology Group (ECOG), World Health Organization (WHO), Zubrod Scale Healthy volunteer subjects will be identified from the general population. Healthy subjects will be screened via inclusion/exclusion criteria upon contact. If appropriate for participation, the subject will be consulted for consent.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 668
• Est. completion date: July 24, 2025
• Est. primary completion date: July 22, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• presence in the surgery or trauma intensive care unit (ICU) at University of Florida (UF) Health Shands Hospital where clinical care can be managed by surgical critical care guided by standard operating procedures.
• age of =18 years
• placed on EMR sepsis protocol with sepsis/septic shock by Sepsis-3 criteriad
• ability to obtain informed consent.

Exclusion Criteria:

• patients deemed to be futile care or have advanced care directives or goals of care limiting resuscitative efforts.
• severe traumatic brain injury (evidence of neurologic injury on CT scan and a Glasgow Coma Scale (GCS) <8 after resuscitation).
• refractory shock (i.e., patients who die within 12 hours).
• uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel)
• severe Congestive Heart Failure (CHF) (NY Heart Association Class IV)
• severe chronic liver disease (Childs-Pugh Class B/C and /or MELD > 14) or pre-liver transplant.
• known HIV infection with CD4 count <200 cells/mm3
• organ transplant recipient on immunosuppressive agents
• known pregnancy
• prisoners
• institutionalized patients
• inability to obtain informed consent.
• pre-hospital bedridden status (WHO/Zubrod score = 4).
• patient's with an exacerbation of historic CVD or new onset CVD
• alternative or confounding diagnosis causing shock state (e.g. MI or PE)
• enrollment > 96 hours after suspected sepsis onset.
• pre-existing state of Chronic critical illness (ICU LOS = 14 days, includes outside facility)
• interfacility transfer patients with > 96 hour critical illness prior to transfer.
• subsequent clinical adjudication not consistent with sepsis/septic shock by Sepsis-3 criteria Healthy Controls

Inclusion criteria will be:

• all adults (age =18)
• Ability to obtain Informed Consent prior to blood collection.

Exclusion Criteria will be:

• Current, chronic steroid use
• Pregnancy

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Other:
• Blood collection
Blood will be collected from patient at baseline, day 1, day 4, day 7 and weekly until week 6 as long as the patient is still hospitalized. Blood will also be collected at the one year appointment.
• Urine collection
Urine will be collected from patient at baseline, day 1, day 4, day 7 and weekly until week 6 as long as the patient is still hospitalized. Urine will also be collected at the one year appointment.
• Bioimpedance Analysis
The bioimpedance analysis will be performed at baseline, day 14 or discharge from hospitalization, month 3, month 6, and month 12.
• Cognitive Function Tests
Cognitive function tests will be administered at 3, 6 and 12 months.
• Quality-of-life Questionnaires
Quality-of-life questionnaires will be administered at baseline, 3, 6 and 12 months.
• Physical Function Tests
Physical function tests will be administered at baseline, day 14 or discharge from hospital 3, 6 and 12 months.
• Blood Collection
The healthy volunteer participants will donate a blood sample. These controls will allow the investigators to determine if the values obtained are accurate, reliable, and repeatable.

Locations

Country	Name	City	State
United States	UF Health Shands Hospital	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	American Heart Association, National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	Mortality will be assessed daily while the subject is in the hospital and then at post discharge follow up visits or by phone if the subject is unable to come to the follow up appointments. The Social Security mortality database will be accessed for subjects that are lost to follow up.	Up to one year
Primary	A change in the results in blood markers for persistent inflammatory state from baseline, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, and one year.	Participant's blood will be analyzed for a persistent inflammatory state, anemia and adaptive immunosuppression. To look at whether sepsis alters the angiogenic balance between angiotensin II (ANGII), erythropoietin, and the VEGF receptor (VEGFR), and whether this imbalance is required for myeloid-derived suppressor cell (MDSC) expansion and chronic critical illness (CCI) and catabolism syndrome (PICS) development.	Baseline, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, and one year.
Primary	A change in the results for mRNA isolation and protein biomarkers from baseline, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, and one year.	The urine will be processed for mRNA isolation and protein biomarkers.	Baseline, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, and one year.
Primary	A change in the results of the Dys-HDL baseline to day 4	Participant's blood will be analyzed to extensively characterize the temporal relationship between Dys-HDL, pertinent enzymes, and sepsis and endothelial biomarkers in patients with sepsis.	Baseline and Day 4
Secondary	A change in results from the Hopkins Verbal Learning Test from 3 months, 6 months and one year.	A 12-item learning and memory test designed for brief, easy administration with proven participant tolerability in a variety of populations. The highest score is 36 and the lowest score is 12. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	3 months, 6 months and one year.
Secondary	A change in results from the Controlled Oral Word Association from 3 months, 6 months and one year.	Measures executive function and verbal fluency. Patients are asked to generate as many words as possible beginning with specific letters. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	3 months, 6 months and one year.
Secondary	a change iin the results from the Modified Mini-Mental Status Exam from 3 months, 6 months and one year.	A measure of global cognitive functioning. This is an expanded 100- point version of the original Folstein Modified Mini-Mental Status Exam. A score greater than or equal to 27 overall points indicates a normal cognition, below this score can indicate severe (-9), moderate (10-18) or mild (19 -24) cognitive impairment. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	3 months, 6 months and one year.
Secondary	A change in the results form the Health-related Quality of Life questionnaire from baseline, 3 months, 6 months and one year.	The Medical Outcome Study 36-item short form (SF-36) is a measure of health-related quality of life (HRQOL). It scores eight domains of health: physical functioning, role limitations due to physical health, role limitations due to emotional problems, vitality (energy/fatigue), mental health, bodily pain, social functioning, and general health perceptions on a scale from 0 to 100, with 100 representing the highest level of functioning possible. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	Baseline, 3 months, 6 months and one year.
Secondary	A change in the results from the EuroQol-5D (EQ-5D) questionnaire from baseline, 3 months, 6 months and one year.	The EQ-5D is an HRQOL instrument with established validity in critical care survivors and as a surrogate-completed proxy measure. This tool is a descriptive system of health-related quality-of-life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can take one of three responses. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	Baseline, 3 months, 6 months and one year.
Secondary	A change in the results of the Mini Nutritional Assessment Form (MNA-SF) baseline, 3 months, 6 months and one year.	This is a validated nutrition screening and assessment tool that can identify patients who are malnourished or at risk for malnutrition. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	Baseline, 3 months, 6 months and one year.
Secondary	A change in the results of the Short Physical Performance Battery from 3 months, 6 months and one year.	Based on a timed short-distance (4 min) walk, repeated chair stands, and balance test. A score of 0 to 4 will be determined for each component, and a summary score ranging from 0 (worst performers) to 12 (best performers) will be calculated. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	3 months, 6 months and one year.
Secondary	A change in the results of the Hand Grip Strength Measurement from baseline, day 14 or discharge from hospital, 3 months, 6 months and one year.	Using an adjustable, hydraulic grip strength dynamometer. Three trials will be conducted for each hand. The best performance for each hand will be recorded. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	baseline, 14 days or hospital discharge, 3 months, 6 months and one year.
Secondary	A change in the results from The ECOG/WHO/Zubrod Scale from 3 months, 6 months and one year.	A 5-point scale that measures the performance status of a patient's ambulatory nature: 0) Asymptomatic (fully active), 1) Symptomatic but completely ambulatory (restricted in physically strenuous activity), 2) Symptomatic, <50% in bed during the day (ambulatory and capable of all selfcare but unable to perform any work activities), 3) Symptomatic, >50% in bed, but not bedbound (capable of only limited self-care), 4) Bedbound (completely disabled, incapable of any self-care), and 5) Death. The test will be performed to look at the epidemiology and long-term physical and cognitive outcomes of chronic critical illness (CCI) in surgical intensive care unit (ICU) participants who survive sepsis.	3 months, 6 months and one year.
Secondary	A change in the results from the Bioimpedance analysis from baseline, day 14 or hospital discharge, 3 months, 6 months, and one year.	Using a Biodynamics BIA 450 to measure the content of water, muscle and fat to assess body composition	baseline, 14 days or hospital discharge, 3 months, 6 months, and one year.