Clinical trial NCT02276417: PICS: Subtitle Cardiac Dysfunction in Older Sepsis Survivors
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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Sepsis
Keywords: Sepsis
Surgical ICU
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
name: American Heart Association
First posted: 2014-10-28
Enrollment: 668
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: We are looking at all patients admitted to the surgical and trauma ICUs that have been entered into the sepsis protocol.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Baseline, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, and one year.
measure: 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.
timeFrame: Baseline, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, and one year.
measure: A change in the results of the Dys-HDL baseline to day 4
timeFrame: Baseline and Day 4
Secondary outcomes:
measure: A change in results from the Hopkins Verbal Learning Test from 3 months, 6 months and one year.
timeFrame: 3 months, 6 months and one year.
measure: A change in results from the Controlled Oral Word Association from 3 months, 6 months and one year.
timeFrame: 3 months, 6 months and one year.
measure: a change iin the results from the Modified Mini-Mental Status Exam from 3 months, 6 months and one year.
timeFrame: 3 months, 6 months and one year.
measure: A change in the results form the Health-related Quality of Life questionnaire from baseline, 3 months, 6 months and one year.
timeFrame: Baseline, 3 months, 6 months and one year.
measure: A change in the results from the EuroQol-5D (EQ-5D) questionnaire from baseline, 3 months, 6 months and one year.
timeFrame: Baseline, 3 months, 6 months and one year.
measure: A change in the results of the Mini Nutritional Assessment Form (MNA-SF) baseline, 3 months, 6 months and one year.
timeFrame: Baseline, 3 months, 6 months and one year.
measure: A change in the results of the Short Physical Performance Battery from 3 months, 6 months and one year.
timeFrame: 3 months, 6 months and one year.
measure: 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.
timeFrame: baseline, 14 days or hospital discharge, 3 months, 6 months and one year.
measure: A change in the results from The ECOG/WHO/Zubrod Scale from 3 months, 6 months and one year.
timeFrame: 3 months, 6 months and one year.
measure: A change in the results from the Bioimpedance analysis from baseline, day 14 or hospital discharge, 3 months, 6 months, and one year.
timeFrame: baseline, 14 days or hospital discharge, 3 months, 6 months, and one year.
Other outcomes:
measure: Mortality
timeFrame: Up to one year
Locations:
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
Study officials:
affiliation: University of Florida
name: Philip Efron, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stortz JA, Cox MC, Hawkins RB, Ghita GL, Brumback BA, Mohr AM, Moldawer LL, Efron PA, Brakenridge SC, Moore FA. Phenotypic heterogeneity by site of infection in surgical sepsis: a prospective longitudinal study. Crit Care. 2020 May 7;24(1):203. doi: 10.1186/s13054-020-02917-3.
citation: Hollen MK, Stortz JA, Darden D, Dirain ML, Nacionales DC, Hawkins RB, Cox MC, Lopez MC, Rincon JC, Ungaro R, Wang Z, Wu Q, Brumback B, Gauthier ML, Kladde M, Leeuwenburgh C, Segal M, Bihorac A, Brakenridge S, Moore FA, Baker HV, Mohr AM, Moldawer LL, Efron PA. Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis. Crit Care. 2019 Nov 13;23(1):355. doi: 10.1186/s13054-019-2628-x.
citation: Brakenridge SC, Moore FA, Mercier NR, Cox M, Wu Q, Moldawer LL, Mohr AM, Efron PA, Smith RS. Persistently Elevated Glucagon-Like Peptide-1 Levels among Critically Ill Surgical Patients after Sepsis and Development of Chronic Critical Illness and Dismal Long-Term Outcomes. J Am Coll Surg. 2019 Jul;229(1):58-67.e1. doi: 10.1016/j.jamcollsurg.2019.04.014. Epub 2019 Apr 13.
citation: Gardner AK, Ghita GL, Wang Z, Ozrazgat-Baslanti T, Raymond SL, Mankowski RT, Brumback BA, Efron PA, Bihorac A, Moore FA, Anton SD, Brakenridge SC. The Development of Chronic Critical Illness Determines Physical Function, Quality of Life, and Long-Term Survival Among Early Survivors of Sepsis in Surgical ICUs. Crit Care Med. 2019 Apr;47(4):566-573. doi: 10.1097/CCM.0000000000003655.
citation: Stortz JA, Mira JC, Raymond SL, Loftus TJ, Ozrazgat-Baslanti T, Wang Z, Ghita GL, Leeuwenburgh C, Segal MS, Bihorac A, Brumback BA, Mohr AM, Efron PA, Moldawer LL, Moore FA, Brakenridge SC. Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients. J Trauma Acute Care Surg. 2018 Feb;84(2):342-349. doi: 10.1097/TA.0000000000001758.