Clinical trial NCT02871895: Application of Biomarkers Change to Predict Outcome of Patient With Severe Sepsis
Official title: Application of Biomarkers Change to Predict Outcome of Patients With Severe Sepsis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Systemic Inflammatory Response Syndrome (SIRS)
Sepsis
Severe Sepsis
Septic Shock
Multiple Organ Failure
Keywords: sepsis
severe sepsis
septic shock
multiple organ failure
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2016-08-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be conducted at Kaohsiung Chang Gung Memorial Hospital. All adult patients presenting with sepsis or severe sepsis will be enrolled on admission to medical intensive units (total 34 beds). Sepsis and severe sepsis are defined as American College of Chest Physicians/Society of Critical Care Medicine consensus criteria for sepsis syndromes.

Brief summary: In 2004, the Surviving Sepsis Campaign (SSC) introduced guidelines for the management of severe sepsis and septic shock, as well as strategies for bedside implementation. The treatment recommendations were organized in two bundles. In an international study, enrolling adult patients with severe sepsis admitted to these intensive care units, investigators found that while mortality from severe sepsis is high (44.5%), compliance with resuscitation and management bundles is generally poor in much of Asia. Investigators need to identify the patients at risk for high in-hospital mortality in order to take appropriate steps.

From their past studies, investigators found that sepsis involved inflammation and coagulation. The multiple organ involvement was associated with interaction of novel biomarkers such as cytokines. There is limited data regarding comparing and application of biomarkers of different characteristic on sepsis treatment. A simultaneous detection of multiple cytokines may provide significant prognostic information. For other biomarkers, promising observation data have been put forward, but their potential needs to be evaluated in large-scale, well-designed prospective intervention studies before clinical use can be recommended. Besides many clinical studies on biomarkers were confounded by its lack of standard bundle care for severe sepsis patient.

Here investigators performed a systematic study aimed at evaluating

1. the individual and combined diagnostic accuracy of biomarkers for predicting mortality;
2. whether trend change in biomarker level more useful for above prediction;
3. which biomarker or biomarker combination checked can predict patients at risk of evolving with severe organ dysfunctions.

Detailed description: Variables will be tested for their association with the outcome using Pearson chi-square test for categorical data and Mann-Whitney U test for numerical data. Comparison the different groups will be conducted by using Mann-Whitney U test for numerical data and using Pearson chi-square test for categorical data. The time course of biomarker plasma levels will be assessed by analysis of variance. Multivariate analysis will be performed using a logistic regression model to estimate the odds ratio of organ failure and dying, along with the 95% confidence interval (CI). Forward and backward selection procedures will be used to iteratively select the variables potentially related to death.

Discrimination will be assessed using the area under the receiver operating characteristic curve to evaluate how well the model distinguished patients who lived from those who died and whether progression of organ dysfunction. A survival analysis will be performed using Kaplan-Meier curves and the log-rank test. Analyses will be completed and a two-tailed p\<0.05 will be considered significant.

Eligibility criteria: Inclusion Criteria:

* Severe sepsis
* Septic shock

Exclusion Criteria:

* Patients are \< 18 yrs
* Patients are immunocompromised (treatment with corticosteroids \>1 mg/kg equivalent prednisone)
* Bone marrow or organ transplant recipients,
* Leucopenia \[white blood cells count\< 109/L\] or neutropenia \[polymorphonuclear granulocyte count \<0.5 109/L\]
* Hematologic malignancy
* Acquired immune deficiency syndrome

Primary outcomes:
measure: Development of immune dysfunction score to predict 28-day mortality of sepsis patients
timeFrame: baseline and 4 weeks, up to 24 weeks
Secondary outcomes:
measure: Deteriorated dynamic acute kidney injury (AKI) stage associated with immune dysfunction and higher mortality in Septic Patients Admitted to Intensive Care Unit
timeFrame: baseline and 4 weeks, up to 24 weeks
measure: To determine whether delta pulse pressure at day 3 compared with day 1 affect survival outcomes in patients who were diagnosed sepsis and septic shock.
timeFrame: baseline and 4 weeks
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Wen-Feng Fang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, Gomersall CD, Faruq MO, Shrestha BR, Gia Binh N, Arabi YM, Salahuddin N, Wahyuprajitno B, Tu ML, Wahab AY, Hameed AA, Nishimura M, Procyshyn M, Chan YH; MOSAICS Study Group. Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ. 2011 Jun 13;342:d3245. doi: 10.1136/bmj.d3245.
citation: Jones AE, Puskarich MA. Is lactate the "Holy Grail" of biomarkers for sepsis prognosis? Crit Care Med. 2009 May;37(5):1812-3. doi: 10.1097/CCM.0b013e3181a09487. No abstract available.
citation: Schuetz P, Haubitz S, Mueller B. Do sepsis biomarkers in the emergency room allow transition from bundled sepsis care to personalized patient care? Curr Opin Crit Care. 2012 Aug;18(4):341-9. doi: 10.1097/MCC.0b013e328354b2c8.
citation: Kwak SH, Wang XQ, He Q, Fang WF, Mitra S, Bdeir K, Ploplis VA, Xu Z, Idell S, Cines D, Abraham E. Plasminogen activator inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK-mediated pathway. Thromb Haemost. 2006 May;95(5):829-35.
citation: Wang XQ, Bdeir K, Yarovoi S, Cines DB, Fang W, Abraham E. Involvement of the urokinase kringle domain in lipopolysaccharide-induced acute lung injury. J Immunol. 2006 Oct 15;177(8):5550-7. doi: 10.4049/jimmunol.177.8.5550.
citation: Hoke TS, Douglas IS, Klein CL, He Z, Fang W, Thurman JM, Tao Y, Dursun B, Voelkel NF, Edelstein CL, Faubel S. Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. J Am Soc Nephrol. 2007 Jan;18(1):155-64. doi: 10.1681/ASN.2006050494. Epub 2006 Dec 13.
citation: Lin MC, Leung SY, Fang WF, Chin CH, Chung KF. Down-regulation of insulin-like growth factor I (IGF-I) in the mouse diaphragm during sepsis. Chang Gung Med J. 2010 Sep-Oct;33(5):501-8.