Evaluation of Corticosteroid in Systemic Inflammatory Response Syndrome

NCT03876041 | Completed Phase 4 DMC

• 1 other identifier: ASSUITUU
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Inflammatory Response Syndrome

Keywords

SIRS; MiRNA-155; Treg

Outcome Measures

Primary Outcomes (2)

• measure anti-inflammatory effect through detection T regulatory cell level by4 color flow cytometry analysis to quantify % of Tregs (CD4, CD25,FoxP3)

  in blood of all subjects

  72 hours post operative

• detect microRNA-155

  micro-RNA 155 is measured by RT-PCR

  72 hours post operative

Secondary Outcomes (1)

• measure pro-inflammatory cytokines

  72 hours post operative

Study Arms (2)

dexamethasone group

ACTIVE COMPARATOR

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

methylprednisolone group

ACTIVE COMPARATOR

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

Interventions

solumedrol DRUG

intravenous solution for injection

Also known as: methylprednisolone

methylprednisolone group

Dexamethasone phosphate DRUG

intravenous solution for injection

Also known as: dexamethasone

dexamethasone group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assuit university hospital

Asyut, Assuit, 71511, Egypt

Location

Related Publications (5)

• Cicarelli DD, Bensenor FE, Vieira JE. Effects of single dose of dexamethasone on patients with systemic inflammatory response. Sao Paulo Med J. 2006 Mar 2;124(2):90-5. doi: 10.1590/s1516-31802006000200008.

  PMID: 16878192 BACKGROUND

• Wang D, Tang M, Zong P, Liu H, Zhang T, Liu Y, Zhao Y. MiRNA-155 Regulates the Th17/Treg Ratio by Targeting SOCS1 in Severe Acute Pancreatitis. Front Physiol. 2018 Jun 8;9:686. doi: 10.3389/fphys.2018.00686. eCollection 2018.

  PMID: 29937734 BACKGROUND

• Bocsi J, Hanzka MC, Osmancik P, Hambsch J, Dahnert I, Sack U, Bellinghausen W, Schneider P, Janousek J, Kostelka M, Tarnok A. Modulation of the cellular and humoral immune response to pediatric open heart surgery by methylprednisolone. Cytometry B Clin Cytom. 2011 Jul-Aug;80(4):212-20. doi: 10.1002/cyto.b.20587. Epub 2011 Mar 4.

  PMID: 21374796 BACKGROUND

• Schadenberg AW, Vastert SJ, Evens FC, Kuis W, van Vught AJ, Jansen NJ, Prakken BJ. FOXP3+ CD4+ Tregs lose suppressive potential but remain anergic during transient inflammation in human. Eur J Immunol. 2011 Apr;41(4):1132-42. doi: 10.1002/eji.201040363. Epub 2011 Mar 7.

  PMID: 21381018 BACKGROUND

• Soltani G, Abbasi Tashnizi M, Moeinipour AA, Ganjifard M, Esfahanizadeh J, Sepehri Shamloo A, Purafzali Firuzabadi SJ, Zirak N. Comparing the effect of preoperative administration of methylprednisolone and its administration before and during surgery on the clinical outcome in pediatric open heart surgeries. Iran Red Crescent Med J. 2013 Jun;15(6):483-7. doi: 10.5812/ircmj.8105. Epub 2013 Jun 5.

  PMID: 24349746 BACKGROUND

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome

Interventions

Methylprednisolone Hemisuccinate; Methylprednisolone; dexamethasone 21-phosphate; Dexamethasone

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Alaa F Fathy, researcher

  Assuit Medical school

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investegator

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 15, 2019
• Study Start: September 1, 2019
• Primary Completion: September 1, 2020
• Study Completion: November 1, 2020
• Last Updated: June 14, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)