STUDY00015328: Sepsis Endotypes

Sepsis Clinical Trial

Official title:

Resistin as a Diagnostic and Prognostic Biomarker of Sepsis

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03146546
• Other study ID #: 7188
• Status: Enrolling by invitation
• Start date: August 6, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: August 2023
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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:

1. All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score

2. Demographic variables variables (eg, age, sex, Elixhauser comorbidities)

3. 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:

1. All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score

2. 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:

1. All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score

2. 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:

1. All parameters required to calculate APACHE IV severity of illness score, and SOFA severity of illness score

2. 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 200
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults (age = 18 )

2. gender: male or female

3. 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

4. Clinical suspicion for sepsis (except for control/comparison group for whom infection is NOT a current concern)

Exclusion Criteria:

1. Patients with hematologic malignancies

2. Pregnant women

3. Patient/surrogate is not fluent in English and no translation services are available

4. Long-term immunosuppressive therapy

5. Prisoner

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Locations

Country	Name	City	State
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (8)

Cummings CJ, Martin TR, Frevert CW, Quan JM, Wong VA, Mongovin SM, Hagen TR, Steinberg KP, Goodman RB. Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis. J Immunol. 1999 Feb 15;162(4):2341-6. — View Citation

Delano MJ, Thayer T, Gabrilovich S, Kelly-Scumpia KM, Winfield RD, Scumpia PO, Cuenca AG, Warner E, Wallet SM, Wallet MA, O'Malley KA, Ramphal R, Clare-Salzer M, Efron PA, Mathews CE, Moldawer LL. Sepsis induces early alterations in innate immunity that impact mortality to secondary infection. J Immunol. 2011 Jan 1;186(1):195-202. doi: 10.4049/jimmunol.1002104. Epub 2010 Nov 24. — View Citation

Koch A, Gressner OA, Sanson E, Tacke F, Trautwein C. Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients. Crit Care. 2009;13(3):R95. doi: 10.1186/cc7925. Epub 2009 Jun 19. — View Citation

Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis. 2012 Jun;25(3):321-7. doi: 10.1097/QCO.0b013e3283528c9b. — View Citation

Macdonald SP, Stone SF, Neil CL, van Eeden PE, Fatovich DM, Arendts G, Brown SG. Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department. PLoS One. 2014 Oct 24;9(10):e110678. doi: 10.1371/journal.pone.0110678. eCollection 2014. — View Citation

Singbartl K, Miller L, Ruiz-Velasco V, Kellum JA. Reversal of Acute Kidney Injury-Induced Neutrophil Dysfunction: A Critical Role for Resistin. Crit Care Med. 2016 Jul;44(7):e492-501. doi: 10.1097/CCM.0000000000001472. — View Citation

Stephan F, Yang K, Tankovic J, Soussy CJ, Dhonneur G, Duvaldestin P, Brochard L, Brun-Buisson C, Harf A, Delclaux C. Impairment of polymorphonuclear neutrophil functions precedes nosocomial infections in critically ill patients. Crit Care Med. 2002 Feb;30(2):315-22. doi: 10.1097/00003246-200202000-00009. — View Citation

Sunden-Cullberg J, Nystrom T, Lee ML, Mullins GE, Tokics L, Andersson J, Norrby-Teglund A, Treutiger CJ. Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med. 2007 Jun;35(6):1536-42. doi: 10.1097/01.CCM.0000266536.14736.03. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The expression of BPGM and AP2 transcripts	sepsis-associated gene pathways	5 years for completion of study, 1 year follow up per patient enrolled
Secondary	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
Secondary	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
Secondary	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