Steroid-induced Reduction of Surgical Stress Study

NCT00807521 | Withdrawn

• 1 other identifier: 08/214
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The stress response as induced by myocardial cellular damage during cardiac surgery may lead to myocardial stunning and apoptosis, and could therefore impair postoperative patient recovery. Surgical trauma typically induces the liberation of cytokines. Some of these cytokines are strongly associated with the initiation of intracellular proapoptotic pathways through activation of tyrosine kinases and integrins. The latter are known for their deteriorating effects on cardiac function and are strongly involved in cardiac remodeling. Dexamethasone is typically administered prior to cardiac surgery in order to especially reduce the release of proinflammatory cytokines. It has however never been investigated whether this additionally reduces proapoptotic signaling in the human heart, thereby eliminating risk factors for the induction of cardiac dysfunction. In the present study, the investigators therefore aim to investigate whether dexamethasone inhibits proapoptotic pathways in patients undergoing cardiac surgery. Furthermore, the investigators would like to elucidate whether this proposed effect of dexamethasone is related to the reduction of the stress response in the heart or indirectly by suppression of cytokine release. For this purpose the investigators will obtain cardiac biopsies and plasma from patients, who are randomly assigned to placebo or dexamethasone treatment and undergo on and off-pump coronary artery bypass grafting (CABG) surgery.

Conditions

Coronary Artery Stenosis; Coronary Artery Bypass Graft Surgery

Outcome Measures

Primary Outcomes (1)

• Expression of p38 in cultured cells and cardiac tissue

  One week

Secondary Outcomes (1)

• Pro-apoptotic signaling, precursor peptides of ANP (proANP), vasopressin (Copeptin), proET-1 and Adrenomedullin (proADM). Age, gender, length, body weight, hematocrit, Hb, leukocytes, surgery time, clamp time, CPB time

  One week

Study Arms (2)

1

ACTIVE COMPARATOR

High dose bolus of dexamethasone before surgery

Drug: Dexamethasone

2

PLACEBO COMPARATOR

Placebo control

Drug: Placebo

Interventions

Dexamethasone DRUG

Single high dose bolus of dexamethasone before surgery

1

Placebo DRUG

Placebo for dexamethasone

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing coronary artery bypass surgery (CABG)
• Age 18-75 years
• Informed consent

You may not qualify if:

• Re-operations and emergency operations
• Patient with anemia (Hb \< 5.0)
• Emergency operation
• Patients receiving blood transfusions \< 3 months before operation
• Insulin depended diabetes mellitus
• Hepatic or renal failure
• Pregnancy
• Use of steroids

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Links

• General website of site

MeSH Terms

Conditions

Coronary Stenosis

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jan R. de Jong, MD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• dr. Christa Boer, PhD

  Amsterdam UMC, location VUmc

  STUDY CHAIR

• dr. Everaldo M. Redout, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.dr. C. Boer

Study Record Dates

• First Submitted: December 11, 2008
• First Posted: December 12, 2008
• Study Start: December 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: June 1, 2011
• Last Updated: December 17, 2014

Record last verified: 2014-12

Locations

NL (1)