Evaluation of Corticosteroid in Systemic Inflammatory Response Syndrome

Sponsor

Assiut University (Other)

Overall Status

Completed

CT.gov ID

NCT03876041

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cardiac surgery and cardiopulmonary bypass (CPB) initiate a whole-body systemic inflammatory response (SIRS) characterized by the activation of leukocytes, monocytes, and the complement cascade. Multiple mediators of the inflammatory process are released, including cytokines, endothelin, adhesion molecules, and oxygen free radicals. An exaggerated release of these mediators may contribute to numerous postoperative end-organ complications, including myocardial dysfunction, neurologic impairment, respiratory failure, altered renal and hepatic function, bleeding disorders, and multiple organ failure. Although most cardiac surgical patients do not experience major adverse events, it is likely that the inflammatory response impairs clinical recovery to some degree in all patients.

A large number of therapeutic strategies have been developed to attenuate the inflammatory reaction to CPB and thereby enhance recovery of the cardiac surgical patient. Intraoperative corticosteroid administration has been studied extensively as a primary pharmacologic anti-inflammatory treatment option.

Condition or Disease	Intervention/Treatment	Phase
Systemic Inflammatory Response Syndrome	Drug: solumedrol Drug: Dexamethasone phosphate	Phase 4

Detailed Description

Investigations have shown that clinical outcomes have been improved, worsened, or unaffected by the intraoperative administration of dexamethasone or methylprednisolone Limited data suggest that low-dose corticosteroids may be as effective as high-dose treatment in reducing complications but with fewer potential side effects MicroRNAs (miRNAs) are protein regulators that play an important role in a wide range of cellular functions. There is increasing evidence for the close relationship between miRNA expression, Th17 cell differentiation and disease pathology The miRNA, miR-155, which was the subject of this study, has a range of known biological functions, which include the induction of Toll like receptor (TLR) activation in monocytes /macrophages and the modulation of TLR signaling, facilitating pro-inflammatory cellular responses and initiating systemic inflammatory responses, as well as regulating Treg cell differentiation, maintenance, and function. The expression of this miRNA can be induced by inflammatory cytokines, such as tumor necrosis factor α (TNFα), that are released into the circulation in the initial stages of a systemic inflammatory response. In another study, demonstrated that miR-155 enhanced Treg and Th17 cell differentiation and Th17 cell function by targeting (suppressor of cytokine signaling 1) SOCS1.

In this study, the investigators will compare effect of low dose intra-operative corticosteroid (dexamethasone and methylprednisolone) as anti-inflammatory modulators through detection of T regulatory cells(Tregs) and IL-17 and correlate relation between Treg, IL-17 and micro RNA-155.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Evaluation of Corticosteroid as Modulators of Humeral and Cellular Immune Response in Open Heart Surgery in Egyptian Population

Actual Study Start Date :

Sep 1, 2019

Actual Primary Completion Date :

Sep 1, 2020

Actual Study Completion Date :

Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: dexamethasone group this group will receive Dexamethasone: 0.1 to 0.3 mg/kg as single intra-operative dose and blood samples will be obtained from central venous blood at following time points: immediately after insertion during anesthetic induction (T1), 48hrs post-operative (T2), 72hrs post-operative (T3).	Drug: Dexamethasone phosphate intravenous solution for injection Other Names: dexamethasone
Active Comparator: methylprednisolone group this group will receive Methylprednisolone: 5-10mg/kg as single intra-operative dose and blood samples will be obtained from central venous blood at following time points: immediately after insertion during anesthetic induction (T1), 48hrs post-operative (T2), 72hrs post-operative (T3).	Drug: solumedrol intravenous solution for injection Other Names: methylprednisolone

Arm

Intervention/Treatment

Active Comparator: dexamethasone group

this group will receive Dexamethasone: 0.1 to 0.3 mg/kg as single intra-operative dose and blood samples will be obtained from central venous blood at following time points: immediately after insertion during anesthetic induction (T1), 48hrs post-operative (T2), 72hrs post-operative (T3).

Drug: Dexamethasone phosphate

intravenous solution for injection

Other Names:

dexamethasone

Active Comparator: methylprednisolone group

this group will receive Methylprednisolone: 5-10mg/kg as single intra-operative dose and blood samples will be obtained from central venous blood at following time points: immediately after insertion during anesthetic induction (T1), 48hrs post-operative (T2), 72hrs post-operative (T3).

Drug: solumedrol

intravenous solution for injection

Other Names:

methylprednisolone

Outcome Measures

Primary Outcome Measures

measure anti-inflammatory effect through detection T regulatory cell level by4 color flow cytometry analysis to quantify % of Tregs (CD4, CD25,FoxP3) [72 hours post operative]
in blood of all subjects
detect microRNA-155 [72 hours post operative]
micro-RNA 155 is measured by RT-PCR

Secondary Outcome Measures

measure pro-inflammatory cytokines [72 hours post operative]
pro-inflammatory cytokines such as IL-1 and IL-6 by ELISA.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

open heart surgery with Cardiopulmonary bypass machine with relatively long bypass time more than 60 minute
All patients Included in study with normal heart function

Exclusion Criteria:

Left ventricular ejection fraction less than 40%
acute infection such as sepsis or pneumonia, hepatic and renal failure, cancer or any autoimmune disease
the use of steroid within 2 week prior to operation
coagulation abnormalities