Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion

NCT ID: NCT01377623

Last Updated: 2017-07-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2012-01-31

Brief Summary

The aim of the proposed study is to examine the effect of DEX on the inflammatory response in major surgery. More importantly, the investigators will correlate changes in the concentration of inflammatory mediators with meaningful clinical outcomes.

Detailed Description

Surgical injury to tissue causes a variety of profound physiologic reactions which are essential for the restoration of an organisms' homeostasis. The inflammatory response involves a surge of stress hormones (i.e. ACTH, cortisol, catecholamines), activation of the complement system, migration of leukocytes to the site of injury, the release of cytokines (i.e. interleukins, tumor necrosis factor), as well as other cellular products (i.e. superoxide radicals, proteases, growth factors) (1-3). An appropriate inflammatory cascade is essential for tissue reconstitution and infection control. The associated impairment of multiple organ function is generally mild, because of the physiological reserve of the biological systems. However, a systemic inflammatory response may also lead to postoperative complications in the elderly, neonates, and patients with significant co-morbidity (4, 5). Indeed, mediators of inflammation may induce fatigue and prolong convalescence in healthy patients. On the other hand, dysregulation or suppression of the inflammatory process may lead to improper wound healing, infection and, as demonstrated recently, even an increase in cancer recurrence due to reduction in natural killer cell activity (6, 7).

Anesthetic management may affect both immunostimulatory and immunosuppressive mechanisms either directly by modulating functions of immune cells or indirectly by attenuating the stress response. For example, inhalational anesthetics inhibit neutrophil function and depress lymphocyte proliferation while increasing pro-inflammatory cytokine levels (8, 9)). Propofol also inhibits neutrophil and monocyte function, and has strong anti-inflammatory and anti-oxidative effects (10). Opioids attenuate the direct cell immune response, but have only minimal effects on systemic inflammatory responses (11). It is expected that the choice of anesthetic technique may disturb the balance between pro- and anti-inflammatory responses thus affecting clinical outcomes. A most advantageous anesthetic choice would enhance or have a neutral effect on cellular immunity while minimizing contribution to the systemic inflammatory response.

Conditions

Spinal Stenosis; Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Placebo group

Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Group Type: PLACEBO_COMPARATOR

Placebo group

Intervention Type: DRUG

Fifty six subjects (28 in each arm) will be enrolled. Subjects undergoing one or two level spinal fusion surgery will be screened for eligibility to participate in the study. Subject will be screened, recruited and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Dexmedetomidine group

Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Group Type: EXPERIMENTAL

Dexmedetomidine group

Intervention Type: DRUG

Subjects undergoing one or two level spinal fusion surgery will be screened for eligibility to participate in the study. Subject will be screened, recruited and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Interventions

Dexmedetomidine group

Subjects undergoing one or two level spinal fusion surgery will be screened for eligibility to participate in the study. Subject will be screened, recruited and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Intervention Type: DRUG

Placebo group

Fifty six subjects (28 in each arm) will be enrolled. Subjects undergoing one or two level spinal fusion surgery will be screened for eligibility to participate in the study. Subject will be screened, recruited and randomized during the preadmission visit or the day of surgery. Eligible subjects will be randomized to one of the two treatment group in1:1 ratio to receive either DEX or matching placebo (PBO, LR).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult (> 18) male or female who will undergo surgery for spinal fusion with general anesthesia.

2. If female, subject is non-lactating and is either:

• Not of childbearing potential
• Of childbearing potential but is not pregnant at time of baseline as determined by pre-surgical pregnancy testing.

3. Subject is ASA physical status 1, 2, or 3.

Exclusion Criteria

1. Cognitively impaired (by history)

2. Subject requires chronic antipsychotic history

3. Subject is anticipated to require an additional surgery within 90 days after the intended spinal fusion

4. Subject known to be in liver failure

5. Subject has received treatment with alpha-2-agonist or antagonist within 2 weeks of study entry

6. Subject for whom opiates, benzodiazepines, DEX are contraindicated

7. Chronic use of steroids/NSAIDs

8. Patients with serious bradycardia related arrhythmias, i.e. 2nd degree block.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Bekker, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU School of Medicine

Michael Urban, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital for Special Surgery, New York

Locations

NYU Langone Medical Center, Department of Anesthesiology

New York, New York, United States

Hospital for Special Surgery

New York, New York, United States

Countries

United States

References

Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, Urban M. The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. J Neurosurg Anesthesiol. 2013 Jan;25(1):16-24. doi: 10.1097/ANA.0b013e31826318af.

Reference Type: RESULT

PMID: 22824921 (View on PubMed)

Other Identifiers

10-02185

Identifier Type: -

Identifier Source: org_study_id