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

NCT ID: NCT02871895

Last Updated: 2018-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-07-31

Study Completion Date

2018-12-31

Brief Summary

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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

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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.

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chang Gung Memorial Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wen-Feng Fang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

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Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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ChiHan Huang, Bachelor

Role: CONTACT

886 077317123 ext. 2858

Facility Contacts

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ChiHan Huang, Bachelor

Role: primary

886 077317123 ext. 2858

References

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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. doi: 10.1093/oxfordjournals.ndt.a027256.

Reference Type RESULT
PMID: 8700363 (View on PubMed)

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(Suppl 3):S1-18. doi: 10.1186/cc1860. Epub 2002 Dec 5.

Reference Type RESULT
PMID: 12720570 (View on PubMed)

Salluh JI, Bozza PT. Biomarkers of sepsis: lost in translation? Crit Care Med. 2008 Jul;36(7):2192-4. doi: 10.1097/CCM.0b013e31817c0cd8. No abstract available.

Reference Type RESULT
PMID: 18594226 (View on PubMed)

Shiramizo SC, Marra AR, Durao MS, Paes AT, Edmond MB, Pavao 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.0026790. Epub 2011 Nov 3.

Reference Type RESULT
PMID: 22073193 (View on PubMed)

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. 2007 Apr;35(4):1105-12. doi: 10.1097/01.CCM.0000259463.33848.3D.

Reference Type RESULT
PMID: 17334251 (View on PubMed)

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.

Reference Type RESULT
PMID: 21669950 (View on PubMed)

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.

Reference Type RESULT
PMID: 19373056 (View on PubMed)

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.

Reference Type RESULT
PMID: 22610364 (View on PubMed)

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.

Reference Type RESULT
PMID: 16676075 (View on PubMed)

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.

Reference Type RESULT
PMID: 17015742 (View on PubMed)

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.

Reference Type RESULT
PMID: 17167117 (View on PubMed)

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.

Reference Type RESULT
PMID: 20979700 (View on PubMed)

Other Identifiers

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CMRPG8B1063

Identifier Type: -

Identifier Source: org_study_id

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