STUDY00015328: Sepsis Endotypes

Study Overview
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Brief Summary
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Determine the utility of blood resistin concentrations, when combined with clinical data, for predicting sepsis phenotypes that are associated with poor clinical outcomes. We hypothesize that resistin is a biomarker which provides critical prognostic information when used in conjunction with standard clinical data, in patients with sepsis and septic shock.

Detailed Description
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Day 1 The following will be collected on day 1 of study inclusion: i. Collection of 20ml of blood (preferably from indwelling arterial or central venous catheters which are required for routine medical care of the patient). This sample will be analyzed in the laboratory for the presence of certain chemical biomarkers (resistin, IL-6, nGAL and eNamp) and genetic biomarkers (BPGM and AP2 RNA transcripts) ii. Access to Electronic medical records with documentation of the following variables: All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score Demographic variables variables (eg, age, sex, Elixhauser comorbidities) vital signs (eg, heart rate, respiratory rate, Glasgow Coma Scale score, systolic blood pressure, temperature, and oxygen saturation), markers of inflammation (eg, white blood cell count, premature neutrophil count [also called bands], erythrocyte sedimentation rate, and C-reactive protein), markers of organ dysfunction or injury (eg, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, international normalized ratio, partial pressure of oxygen, platelets, and troponin), and serum levels of glucose, sodium, hemoglobin, chloride, bicarbonate, lactate, and albumin. For each variable, the most abnormal value within 6 hours of hospital presentation will be recorded. The most abnormal of each of these variables in the 24h period will be recorded. Days 2-3 The most abnormal value in each 24-hour period will be documented daily for each of the parameters listed above Day 3-5 i. Collection of 20ml of blood (preferably from indwelling arterial or central venous catheters which are required for routine medical care of the patient. This sample will be analyzed in the laboratory for the presence of certain chemical biomarkers (resistin, IL-6, nGAL and eNamp) and genetic biomarkers (BPGM and AP2 RNA transcripts) ii. Access to Electronic medical records with documentation of the following variables: All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score vital signs (eg, heart rate, respiratory rate, Glasgow Coma Scale score, systolic blood pressure, temperature, and oxygen saturation), markers of inflammation (eg, white blood cell count, premature neutrophil count [also called bands], erythrocyte sedimentation rate, and C-reactive protein), markers of organ dysfunction or injury (eg, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, international normalized ratio, partial pressure of oxygen, platelets, and troponin), and serum levels of glucose, sodium, hemoglobin, chloride, bicarbonate, lactate, and albumin. The most abnormal of each of these variables in the 24h period will be recorded. Days 5-6 The most abnormal value in each 24-hour period will be documented daily for each of the parameters listed above Day 7-10 i. Collection of 20ml of blood (preferably from indwelling arterial or central venous catheters which are required for routine medical care of the patient. This sample will be analyzed in the laboratory for the presence of certain chemical biomarkers (resistin, IL-6, nGAL and eNamp) and genetic biomarkers (BPGM and AP2 RNA transcripts) ii. Access to Electronic medical records with documentation of the following variables: All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score vital signs (eg, heart rate, respiratory rate, Glasgow Coma Scale score, systolic blood pressure, temperature, and oxygen saturation), markers of inflammation (eg, white blood cell count, premature neutrophil count [also called bands], erythrocyte sedimentation rate, and C-reactive protein), markers of organ dysfunction or injury (eg, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, international normalized ratio, partial pressure of oxygen, platelets, and troponin), and serum levels of glucose, sodium, hemoglobin, chloride, bicarbonate, lactate, and albumin. The most abnormal of each of these variables in the 24h period will be recorded. Day 14 (or day of discharge) i. Collection of 20ml of blood (preferably from indwelling arterial or central venous catheters which are required for routine medical care of the patient. This sample will be analyzed in the laboratory for the presence of certain chemical biomarkers (resistin, IL-6, nGAL and eNamp) and genetic biomarkers (BPGM and AP2 RNA transcripts). No more than a total of 1 ml/kg of blood will be collected over the entire study period. ii. Access to Electronic medical records with documentation of the following variables: All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score vital signs (eg, heart rate, respiratory rate, Glasgow Coma Scale score, systolic blood pressure, temperature, and oxygen saturation), markers of inflammation (eg, white blood cell count, premature neutrophil count [also called bands], erythrocyte sedimentation rate, and C-reactive protein), markers of organ dysfunction or injury (eg, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, international normalized ratio, partial pressure of oxygen, platelets, and troponin), and serum levels of glucose, sodium, hemoglobin, chloride, bicarbonate, lactate, and albumin. The most abnormal of each of these variables in the 24h period will be recorded. Day 30, 3 months, 6 months and 1 year: electronic medical record will be reviewed in order to obtain data regarding long-term clinical outcomes. These would include, amongst others, date of death, re-hospitalization and/or persistent critical illness (including APACHE score). Additionally, patients will be contacted by phone at post-hospitalization day 30, 3 months, 6 months and 12 months to collect subjective data via telephone interview about their post-hospitalization course, postoperative complications and need for re-hospitalization (if any). The phone script is designed such that phone calls will last no more than 15 minutes. Duration of Participation 1 year since original hospital admission (which occurs on 'day 1'). Specimens will be obtained from patients as outlined above, until day 14(or last day of hospital admission, if it occurs before day 14) although No more than a total volume of 1 ml/kg of blood will be collected over the entire study period. Patient-related activities following day 14 will be limited to phone calls as described above.

Official Title
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Resistin as a Diagnostic and Prognostic Biomarker of Sepsis

Conditions
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Sepsis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (age ≥ 18 ) gender: male or female Cognitively intact or impaired patients, given that sepsis may cause a certain degree of cognitive dysfunction in patients. All patients in the control group (no sepsis) will be cognitively intact Clinical suspicion for sepsis (except for control/comparison group for whom infection is NOT a current concern) Exclusion Criteria: Patients with hematologic malignancies Pregnant women Patient/surrogate is not fluent in English and no translation services are available Long-term immunosuppressive therapy Prisoner

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sepsis<br>Patients with sepsis as defined by the Sepsis-3 criteria | |
| Control<br>Patients without sepsis, as defined by the Sepsis-3 criteria | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death and chronic critical illness | The primary outcome is a composite binary variable consisting of early death and chronic critical illness which we will determine on or before day 14 after sepsis onset. | 5 years for completion of study, 1 year follow up per patient enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The expression of BPGM and AP2 transcripts | sepsis-associated gene pathways | 5 years for completion of study, 1 year follow up per patient enrolled | 
| Clinical variables | including demographic variables (eg, age, sex, Elixhauser comorbidities), vital signs (eg, heart rate, respiratory rate, Glasgow Coma Scale score, systolic blood pressure, temperature, and oxygen saturation), markers of inflammation (eg, white blood cell count, premature neutrophil count [also called bands], erythrocyte sedimentation rate, and C-reactive protein), markers of organ dysfunction or injury (eg, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, international normalized ratio, partial pressure of oxygen, platelets, and troponin), and serum levels of glucose, sodium, hemoglobin, chloride, bicarbonate, lactate, and albumin. | 5 years for completion of study, 1 year follow up per patient enrolled | 
| Acute Physiology and Chronic Health Evaluation II Score | scale 0-71, with higher scores being worse | 5 years for completion of study, 1 year follow up per patient enrolled | 
| Sequential Organ Failure Assessment | scale of 0-24, with higher scores being worse score | 5 years for completion of study, 1 year follow up per patient enrolled |