PICS: Subtitle Cardiac Dysfunction in Older Sepsis Survivors

NCT02276417 | Active Not Recruiting DMC

• 3 other identifiers: IRB201400611-NP50GM111152-01OCR14760
• Study Type: observational
• Target: 668
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

Sepsis; Surgical ICU

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (10)

• A change in results from the Hopkins Verbal Learning Test from 3 months, 6 months and one year.

  3 months, 6 months and one year.

• A change in results from the Controlled Oral Word Association from 3 months, 6 months and one year.

  3 months, 6 months and one year.

• a change iin the results from the Modified Mini-Mental Status Exam from 3 months, 6 months and one year.

  3 months, 6 months and one year.

• A change in the results form the Health-related Quality of Life questionnaire from baseline, 3 months, 6 months and one year.

  Baseline, 3 months, 6 months and one year.

• A change in the results from the EuroQol-5D (EQ-5D) questionnaire from baseline, 3 months, 6 months and one year.

  Baseline, 3 months, 6 months and one year.

Other Outcomes (1)

• Mortality

  Up to one year

Study Arms (2)

Sepsis

Blood Collection. Urine collection. Bioimpedance analysis. Quality-of-life questionnaires, physical function tests and cognitive function tests.

Other: Blood collection; Other: Urine collection; Other: Bioimpedance Analysis; Other: Cognitive Function Tests; Other: Quality-of-life Questionnaires; Other: Physical Function Tests

Healthy Controls

Blood Collection.

Other: Blood Collection

Interventions

Blood Collection OTHER

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.

Sepsis

Urine collection OTHER

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.

Sepsis

Bioimpedance Analysis OTHER

The bioimpedance analysis will be performed at baseline, day 14 or discharge from hospitalization, month 3, month 6, and month 12.

Also known as: BIA

Sepsis

Cognitive Function Tests OTHER

Cognitive function tests will be administered at 3, 6 and 12 months.

Sepsis

Quality-of-life Questionnaires OTHER

Quality-of-life questionnaires will be administered at baseline, 3, 6 and 12 months.

Sepsis

Physical Function Tests OTHER

Physical function tests will be administered at baseline, day 14 or discharge from hospital 3, 6 and 12 months.

Sepsis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Florida: lead
• National Institute of General Medical Sciences (NIGMS): collaborator
• American Heart Association: collaborator

Study Sites (1)

UF Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

Related Publications (7)

• Barrios EL, Balzano-Nogueira L, Polcz VE, Rodhouse C, Leary JR, Darden DB, Rincon JC, Dirain ML, Ungaro R, Nacionales DC, Larson SD, Sharma A, Upchurch G, Wallet SM, Brusko TM, Loftus TJ, Mohr AM, Maile R, Bacher R, Cai G, Kladde MP, Mathews CE, Moldawer LL, Brusko MA, Efron PA. Unique lymphocyte transcriptomic profiles in septic patients with chronic critical illness. Front Immunol. 2024 Dec 3;15:1478471. doi: 10.3389/fimmu.2024.1478471. eCollection 2024.

  PMID: 39691721 DERIVED

• Barrios EL, Rincon JC, Willis M, Polcz VE, Leary JR, Darden DB, Balch JA, Larson SD, Loftus TJ, Mohr AM, Wallet S, Brusko MA, Balzano-Nogueira L, Cai G, Sharma A, Upchurch GR Jr, Kladde MP, Mathews CE, Maile R, Moldawer LL, Bacher R, Efron PA. TRANSCRIPTOMIC DIFFERENCES IN PERIPHERAL MONOCYTE POPULATIONS IN SEPTIC PATIENTS BASED ON OUTCOME. Shock. 2024 Aug 1;62(2):208-216. doi: 10.1097/SHK.0000000000002379. Epub 2024 May 2.

  PMID: 38713581 DERIVED

• 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.

  PMID: 32381107 DERIVED

• 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.

  PMID: 31722736 DERIVED

• 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.

  PMID: 30991107 DERIVED

• 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.

  PMID: 30664526 DERIVED

• 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.

  PMID: 29251709 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Sepsis

Interventions

Blood Specimen Collection; Urine Specimen Collection

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Philip Efron, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: October 28, 2014
• Study Start: January 1, 2015
• Primary Completion: July 22, 2022
• Study Completion (Estimated): July 24, 2026
• Last Updated: August 28, 2025

Record last verified: 2024-12

Locations

US (1)