Application of Biomarkers Change to Predict Outcome of Patient With Severe Sepsis

Sepsis Clinical Trial

— BCSS  

Official title:

Application of Biomarkers Change to Predict Outcome of Patients With Severe Sepsis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02871895
• Other study ID #: CMRPG8B1063
• Status: Recruiting
• Start date: July 2013
• Est. completion date: December 2018

Study information

• Verified date: June 2018
• Source: Chang Gung Memorial Hospital
• Contact: ChiHan Huang, Bachelor
• Phone: 886 077317123
• Email: cheryl60286[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Organ Failure
• Sepsis
• Septic Shock
• Severe Sepsis
• Shock, Septic
• Systemic Inflammatory Response Syndrome
• Systemic Inflammatory Response Syndrome (SIRS)
• Toxemia

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (12)

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. E — View 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. — View 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. — View 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. — View Citation

Neveu H, Kleinknecht D, Brivet F, Loirat P, Landais P. Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study. The French Study Group on Acute Renal Failure. Nephrol Dial Transplant. 1996 Feb;11(2):293-9. — View Citation

Nguyen HB, Corbett SW, Steele R, Banta J, Clark RT, Hayes SR, Edwards J, Cho TW, Wittlake WA. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med — View 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 — View Citation

Salluh JI, Bozza PT. Biomarkers of sepsis: lost in translation? Crit Care Med. 2008 Jul;36(7):2192-4. doi: 10.1097/CCM.0b013e31817c0cd8. — View 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. Review. — View Citation

Shiramizo SC, Marra AR, Durão MS, Paes ÂT, Edmond MB, Pavão dos Santos OF. Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. PLoS One. 2011;6(11):e26790. doi: 10.1371/journal.pone.002679 — View Citation

Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G. Reducing mortality in sepsis: new directions. Crit Care. 2002 Dec;6 Suppl 3:S1-18. Epub 2002 Dec 5. Review. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of immune dysfunction score to predict 28-day mortality of sepsis patients	Several existing scoring systems developed for mortality prediction, such as APACHE II and Sequential Organ Failure Assessment score (SOFA score). However, none of these take immune dysfunction status into account. With a substantial degree of heterogeneity in the sepsis response ranging from cytokines storm to immunoparalysis, better patient stratification is needed. Investigators aimed to develop and validate a scoring system (minimum:0 to maximum:6 scores) that can determine patients' immune dysfunction status related to outcomes.	baseline and 4 weeks, up to 24 weeks
Secondary	Deteriorated dynamic acute kidney injury (AKI) stage associated with immune dysfunction and higher mortality in Septic Patients Admitted to Intensive Care Unit	A series of inflammatory cytokines participated into the mechanism and associated with the severity and worsening of AKI. We assumed the dynamic change of the AKI containing even better predictive value rather than evaluating the AKI in a single time point. We categorized septic patients into 4 groups based on the variation of AKI stage. In addition to mortality comparison, we also made an investigation to the relationships of immune cytokines in those sepsis patients.	baseline and 4 weeks, up to 24 weeks
Secondary	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.	Pulse pressure is the difference between the systolic and diastolic blood pressures. It arises from the interaction of cardiac ejection and the properties of the arterial circulation. A wide pulse pressure is associated with increased cardiovascular mortality. However, a widened pulse pressure was suggested as a potential prognostic indicator of decreased mortality in patients with sepsis in a retrospective electronic medical record review. In clinical practice, pulse pressure variation can help predict fluid responsiveness in patients. Furthermore, we sought to determine whether stratification of septic patients according to the changes of pulse pressure (value of pulse pressure at day 3 minus value of pulse pressure at day 1) and status of whether still in need of vasopressor at day 3 could help predict survival. The host immune response to sepsis during progression may play an important role.	baseline and 4 weeks