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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01377623
• Collaborator: Hospira, now a wholly owned subsidiary of Pfizer (Industry)
• Enrollment: 66
• Locations: 2
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 33
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Stenosis; Inflammation	Drug: Dexmedetomidine group; Drug: Placebo group	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Pilot Study on the Effect of Dexmedetomidine on Inflammatory Responses in Patients Undergoing Lumbar Spinal Fusion
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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).	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).
Experimental: 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).	Drug: 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).

Outcome Measures

Primary Outcome Measures

1. Quality of Recovery Score (QoR-40) [Post-operative Day 3]

   The QoR-40 is a 40 item questionnaire in which each question is answered with a score of 1-5. QoR-40 scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery).

Secondary Outcome Measures

1. Concentration of TNF-alpha [Post-operative Day 1]

2. Concentration of IL-1a [Post-operative Day 1]

3. Concentration of IL-6 [Post-operative Day 1]

4. Concentration of IL-8 [Post-operative Day 1]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Langone Medical Center, Department of Anesthesiology	New York	New York	United States	10016
2	Hospital for Special Surgery	New York	New York	United States	10021

Sponsors and Collaborators

• NYU Langone Health
• Hospira, now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Alex Bekker, MD, PhD, NYU School of Medicine
• Principal Investigator: Michael Urban, MD, Hospital for Special Surgery, New York

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT01377623
• Other Study ID Numbers: 10-02185
• First Posted: Jun 21, 2011
• Last Update Posted: Jul 11, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by NYU Langone Health: Spinal fusion; Inflammatory response; Inflammatory markers; Dexmedetomidine
• Additional relevant MeSH terms: Spinal Stenosis; Inflammation; Dexmedetomidine

Study Results

Participant Flow

Arm/Group Title	Dexmedetomidine Group (PFD)	Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine	Anesthesia maintained with propofol/fentanyl/saline
Period Title: Overall Study
STARTED	33	33
COMPLETED	26	28
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	Placebo Group	Dexmedetomidine Group	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	28	26	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (11.1)	55.3 (12.3)	56.18 (11.69)
Sex: Female, Male (Count of Participants)
Female	13 46.4%	5 19.2%	18 33.3%
Male	15 53.6%	21 80.8%	36 66.7%

Outcome Measures

1. Primary Outcome

Title	Quality of Recovery Score (QoR-40)
Description	The QoR-40 is a 40 item questionnaire in which each question is answered with a score of 1-5. QoR-40 scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery).
Time Frame	Post-operative Day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine Group (PFD)	Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine	Anesthesia maintained with propofol/fentanyl/saline
Measure Participants	26	28
Mean (Standard Deviation) [units on a scale]	183.04 (2.76)	169.3 (3.87)

2. Secondary Outcome

Title	Concentration of TNF-alpha
Time Frame	Post-operative Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine Group (PFD)	Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine	Anesthesia maintained with propofol/fentanyl/saline
Measure Participants	26	28
Median (Inter-Quartile Range) [pg/ml]	10.1	7.9

3. Secondary Outcome

Title	Concentration of IL-1a
Time Frame	Post-operative Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine Group (PFD)	Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine	Anesthesia maintained with propofol/fentanyl/saline
Measure Participants	26	28
Median (Inter-Quartile Range) [pg/ml]	2.52	2.58

4. Secondary Outcome

Title	Concentration of IL-6
Time Frame	Post-operative Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine Group (PFD)	Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine	Anesthesia maintained with propofol/fentanyl/saline
Measure Participants	26	28
Median (Inter-Quartile Range) [pg/ml]	60.8	50.0

5. Secondary Outcome

Title	Concentration of IL-8
Time Frame	Post-operative Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexmedetomidine Group (PFD)	Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine	Anesthesia maintained with propofol/fentanyl/saline
Measure Participants	26	28
Median (Inter-Quartile Range) [pg/ml]	20.9	16.4

Adverse Events

Arm/Group Title	Dexmedetomidine Group (PFD)		Placebo Group (PFS)
Arm/Group Description	Anesthesia maintained with propofol/fentanyl/dexmedetomidine		Anesthesia maintained with propofol/fentanyl/saline
All Cause Mortality
	Dexmedetomidine Group (PFD)		Placebo Group (PFS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexmedetomidine Group (PFD)		Placebo Group (PFS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Dexmedetomidine Group (PFD)		Placebo Group (PFS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.