Immune Profile of Patients With Sepsis

Sepsis, Severe Clinical Trial

— IPSEPSIS  

Official title:

Immune Profile of Patients With Positive Blood Cultures and Multiple Organ Dysfunctions

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04163705
• Other study ID #: Hospital El Cruce
• Status: Not yet recruiting
• Start date: December 1, 2019
• Est. completion date: July 1, 2020

Study information

• Verified date: November 2019
• Source: Hospital El Cruce
• Contact: Nestor Pistillo, MD
• Phone: 54-011 4210-9000
• Email: npistillo[@]yahoo.com.ar
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The immune response can acquire different profiles (proinflammatory and anti-inflammatory response) depending on the activating agent.The objective of this study is to compare the immunological profile in patients with severe sepsis and positive blood cultures.

Description:

Sepsis is one of the leading causes of death in patients admitted to intensive care. It is characterized by being an exaggerated and deregulated inflammatory response triggered by an infection. Although inflammation affects the compartmentalization of the infection, the activation of the immune system in sepsis has a systemic problem, which sometimes affects the organs distant from the site of infection. Within this context, two processes are recognized, which can often coexist: the pro-inflammatory response and the anti-inflammatory response. While it is assumed that the proinflammatory response may favor the development of multiple organ failure, sepsis-induced immunosuppression would favor a new infection, especially of endogenous and intranosocomial germs, mortality increases. The pro-anti-inflammatory nature of sepsis (if so can be defined) depends on a multitude of factors: the type of infection, personal history, genetic conditions, associated diseases, environmental factors, the use of immunosuppressive medications and nutrition. state, among others. Recent studies found that the immune response profile differs depending on the type of infection (Gram negative or Gram positive). Defining the predominant immune condition is not a simple task. Here there are no commonly used clinical variables that define the immune status, except for neutrophil counts.

Objetive:

• Define whether there are differences in the immunological profile between patients with sepsis and positive blood cultures by Gram negative and Gram positive.

• Identify easily accessible clinical and / or laboratory patterns that can predict the predominant immune character.

Design: The study was approved by the Scientific and Ethics committee of the institution. Informed consent will be requested.

Patients with severe sepsis and positive blood cultures will be included prospectively, within 24 hours of diagnosis of sepsis.

Consider severe sepsis to life-threatening organic dysfunction caused by a deregulated host response to infection. This concept includes at least a score of the SOFA (sequential evaluation of organic insufficiency) scale equal to or greater than 2 points The presence of one or more positive samples will be considered positive blood cultures.

Patients with severe sepsis will be enrolled prospectively and consecutively. Some of the blood used for blood culture samples will be processed for the study (sample 0). The plasma will be stored at -80 ° for later analysis. A routine clinical and laboratory database will be completed.

Only patients who have positive blood cultures will be randomized according to their result in: sepsis by Gram positive or Gram negative.

Patients with severe sepsis but with negative blood cultures will be considered a control group. In patients with positive blood cultures, new blood samples will be taken between days 3 to 5 of sample 0 to define the evolution of the pro and anti-inflammatory response.

Minimum 12 patients per group will be included. The level of proinflammatory cytokines (TNF alpha and IL 1) and anti-inflammatory (IL10 and IL1 receptor) will be measured by ELISA method. Finally, the data will be analyzed and the differences between patients with Gram-positive and Gram-negative infections will be established.

Primary Outcome Measure:

Measurement of the pro-inflammatory and anti-inflammatory response in patients with severe sepsis and positive blood cultures

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: July 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria: severe sepsis -

Exclusion Criteria:

VIH immunosuppression Autoimmune disease Neoplasm Pregnant women Cirrhosis Bone Marrow Disease Malnutrition.

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Related Conditions & MeSH terms

• Sepsis
• Sepsis, Severe

Intervention

Diagnostic Test:
• blood sample collection
Routine Laboratory Analysis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospital El Cruce

References & Publications (9)

Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005 Jan 1-7;365(9453):63-78. Review. — View Citation

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af. — View Citation

Endo S, Inada K, Inoue Y, Kuwata Y, Suzuki M, Yamashita H, Hoshi S, Yoshida M. Two types of septic shock classified by the plasma levels of cytokines and endotoxin. Circ Shock. 1992 Dec;38(4):264-74. — View Citation

Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013 Jan-Feb;50(1):23-36. doi: 10.3109/10408363.2013.764490. Review. — View Citation

Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016 May 23;353:i1585. doi: 10.1136/bmj.i1585. Review. — View Citation

Guenter CA, Hinshaw LB. Comparison of septic shock due to gram-negative and gram-positive organisms. Proc Soc Exp Biol Med. 1970 Jul;134(3):780-3. — View Citation

Janols H, Bergenfelz C, Allaoui R, Larsson AM, Rydén L, Björnsson S, Janciauskiene S, Wullt M, Bredberg A, Leandersson K. A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases. J Leukoc Biol. 2014 No — View Citation

Minasyan H. Sepsis and septic shock: Pathogenesis and treatment perspectives. J Crit Care. 2017 Aug;40:229-242. doi: 10.1016/j.jcrc.2017.04.015. Epub 2017 Apr 18. Review. — View Citation

Zeni F, Vindimian M, Pain P, Gery P, Tardy B, Bertrand JC. Antiinflammatory and proinflammatory cytokines in patients with severe sepsis. J Infect Dis. 1995 Oct;172(4):1171-2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of the proinflammatory response.	Plasma level comparison of: TNF-alpha, IL-6 and IL-1 between both groups, by flow cytometry.	Six months
Primary	Comparison of the anti-inflammatory response	Plasma level comparison of: TNF-alpha receptor, INF-gamma and IL-10 between both groups, by flow cytometry.	Six months
Secondary	Mortality comparison	Mortality between both groups will be compared for the 28th day of admission to the protocol.	Six months
Secondary	SOFA score comparison	Multiple organ dysfunction will be measured with the SOFA score at the time of admission to the protocol and between days 3 to 5. The severity score will be compared between groups.	Six months