- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02276417
PICS: Subtitle Cardiac Dysfunction in Older Sepsis Survivors (PICS)
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 Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Florida
-
Gainesville, Florida, United States, 32610
- UF Health Shands Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Sepsis
Blood Collection.
Urine collection.
Bioimpedance analysis.
Quality-of-life questionnaires, physical function tests and cognitive function tests.
|
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 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.
The bioimpedance analysis will be performed at baseline, day 14 or discharge from hospitalization, month 3, month 6, and month 12.
Other Names:
Cognitive function tests will be administered at 3, 6 and 12 months.
Quality-of-life questionnaires will be administered at baseline, 3, 6 and 12 months.
Physical function tests will be administered at baseline, day 14 or discharge from hospital 3, 6 and 12 months.
|
Healthy Controls
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: 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.
Time Frame: 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
Time Frame: Baseline and 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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
A change in results from the Hopkins Verbal Learning Test from 3 months, 6 months and one year.
Time Frame: 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.
|
A change in results from the Controlled Oral Word Association from 3 months, 6 months and one year.
Time Frame: 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.
|
a change iin the results from the Modified Mini-Mental Status Exam from 3 months, 6 months and one year.
Time Frame: 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.
|
A change in the results form the Health-related Quality of Life questionnaire from baseline, 3 months, 6 months and one year.
Time Frame: 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.
|
A change in the results from the EuroQol-5D (EQ-5D) questionnaire from baseline, 3 months, 6 months and one year.
Time Frame: 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.
|
A change in the results of the Mini Nutritional Assessment Form (MNA-SF) baseline, 3 months, 6 months and one year.
Time Frame: 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.
|
A change in the results of the Short Physical Performance Battery from 3 months, 6 months and one year.
Time Frame: 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.
|
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.
Time Frame: baseline, 14 days or hospital discharge, 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.
|
A change in the results from The ECOG/WHO/Zubrod Scale from 3 months, 6 months and one year.
Time Frame: 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.
|
A change in the results from the Bioimpedance analysis from baseline, day 14 or hospital discharge, 3 months, 6 months, and one year.
Time Frame: baseline, 14 days 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.
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality
Time Frame: Up to one year
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Philip Efron, MD, University of Florida
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB201400611-N
- P50GM111152-01 (U.S. NIH Grant/Contract)
- OCR14760 (Other Identifier: Universiy of Florida)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sepsis
-
University of Kansas Medical CenterUniversity of KansasRecruitingSepsis | Septic Shock | Sepsis Syndrome | Sepsis, Severe | Sepsis Bacterial | Sepsis BacteremiaUnited States
-
Jip GroenInBiomeRecruitingMicrobial Colonization | Neonatal Infection | Neonatal Sepsis, Early-Onset | Microbial Disease | Clinical Sepsis | Culture Negative Neonatal Sepsis | Neonatal Sepsis, Late-Onset | Culture Positive Neonatal SepsisNetherlands
-
Karolinska InstitutetÖrebro University, SwedenCompletedSepsis | Sepsis Syndrome | Sepsis, SevereSweden
-
The University of QueenslandRoyal Brisbane and Women's HospitalUnknown
-
Indonesia UniversityCompletedSevere Sepsis With Septic Shock | Severe Sepsis Without Septic ShockIndonesia
-
Ohio State UniversityCompletedSepsis, Severe Sepsis and Septic ShockUnited States
-
Beckman Coulter, Inc.Biomedical Advanced Research and Development AuthorityRecruitingSevere Sepsis | Severe Sepsis Without Septic ShockUnited States
-
University of LeicesterUniversity Hospitals, Leicester; The Royal College of AnaesthetistsCompletedSepsis | Septic Shock | Severe Sepsis | Sepsis SyndromeUnited Kingdom
-
Zagazig UniversityRecruitingSepsis-associated EncephalopathyEgypt
-
Weill Medical College of Cornell UniversityNational Heart, Lung, and Blood Institute (NHLBI); New York Presbyterian Hospital and other collaboratorsCompletedSepsis | Septic Shock | Severe Sepsis | Infection | Sepsis SyndromeUnited States
Clinical Trials on Blood collection
-
University of FloridaEunice Kennedy Shriver National Institute of Child Health and Human Development...Active, not recruiting
-
University of South AlabamaRecruitingBurns | TraumaUnited States
-
University of OxfordMahidol Oxford Tropical Medicine Research UnitUnknown
-
Skane University HospitalLund University; Region SkaneActive, not recruitingSepsis | Critical Illness | Covid19 | Trauma | Influenza | Cardiac ArrestSweden
-
University of FloridaNational Institutes of Health (NIH); DiaCarta, Inc.Completed
-
Assistance Publique Hopitaux De MarseilleNot yet recruiting
-
Assistance Publique - Hôpitaux de ParisFonds IMMUNOVCompleted
-
SWOG Cancer Research NetworkNational Cancer Institute (NCI)RecruitingSeminoma | Germ Cell Tumor | Metachronous Malignant Neoplasm | Stage I Testicular Cancer AJCC v8 | Stage IA Testicular Cancer AJCC v8 | Stage IB Testicular Cancer AJCC v8 | Stage IS Testicular Cancer AJCC v8Canada, United States, Guam
-
Sir Run Run Shaw HospitalNot yet recruitingCatheter ComplicationsChina
-
GlaxoSmithKlineCompleted