Immunomodulation, IL-1 Inhibition, and Postoperative Incisional Pain

• ClinicalTrials.gov Identifier: NCT01466764
• Recruitment Status: Terminated
• First Posted: November 8, 2011
• Results First Posted: July 6, 2017
• Last Update Posted: August 9, 2017
• Sponsor: Stanford University
• Information provided by (Responsible Party): Gary Peltz, Stanford University

Study Description

Brief Summary:

The investigators hypothesize that perioperative administration of anakinra will reduce incisional pain by lowering the concentration of inflammatory mediators in surgical wounds. This knowledge is important because it suggests a new, previously unexplored pharmacological target for the control of postoperative incisional pain.

Condition or disease	Intervention/treatment	Phase
Pain; Inflammation	Drug: Anakinra; Other: Normal Saline	Not Applicable

Detailed Description:

This study will test whether administration of anakinra, an IL-1 receptor antagonist, will decrease pain and improve wound healing in patients undergoing vascular or orthopedic surgical procedures. The investigators will administer two doses of Anakinra via an injection under the skin, one dose one hour before surgery and a second dose on the first postoperative day (24 hours after surgery). The investigators will remove fluid from the surgical incisions using a small plastic catheter placed under skin during surgery and measure the amounts of pain- causing inflammatory mediators. The investigators will also measure the amount of pain the participant is experiencing using questions about pain intensity and by gently touching the incision to determine sensitivity of the incision site.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Immunomodulation, IL-1 Inhibition, and Postoperative Incisional Pain
• Study Start Date: October 2011
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Anakinra; Two subcutaneous injections of anakinra (IL-1ra) were given, the first one hour prior to surgery and the second 24 hours after surgery.	Drug: Anakinra; An injection of 100 mg Anakinra was administered 1 hour prior to surgery and again 24 hours following surgery.; Other Name: Kineret
Placebo Comparator: Saline injection; Two subcutaneous injections of normal saline (same volume as the anakinra group injection) were given, the first one hour prior to surgery and the second 24 hours after surgery.	Other: Normal Saline; An injection of normal saline was administered 1 hour prior to surgery and again 24 hours following surgery.; Other Name: No other name

Outcome Measures

Primary Outcome Measures :

1. Concentration Levels of Inflammatory Mediators IL-1 Receptor Antagonist (IL-1ra) Present in Human Wounds Following Surgery With and Without the Use of Anakinra. [ Time Frame: Up to 72 hours following surgery ]
   Tissue samples were collected at the surgical wound site at 3 time points during the 1st 72 hours following surgery. Tissue samples from subjects receiving placebo, and subjects receiving anakinra injections pre, and post op were analyzed for IL-1

Secondary Outcome Measures :

1. Number of Participants With Analgesic Consumption During the 72 Hours Following Surgery [ Time Frame: Up to 72 hours following surgery ]

   Analgesic consumption is reported as the count of participants receiving each analgesic type. Comparisons between the placebo and active drug groups were made at the conclusion of the study.

   PCA/IV: Patient controlled Analgesia/ Intravenous

2. Post-operative Pain Intensity [ Time Frame: Up to 72 hours following surgery ]
   Pain was measured on Day 1 and day 2 following surgery using a VAS scale at rest and on stimulation with Visual Analog Scale (VAS) of 1-10 (1=no pain and 10=worst pain)
3. Count of Participants Experiencing Wound Infection in the Study From Surgery Till the Time of Discharge From the Hospital [ Time Frame: Up to 72 hours following surgery plus 3 weeks follow-up ]
   Evaluation of the surgical wound for symptoms of wound infection was made every day during hospitalization. Records from the first post-operative clinic visit were also evaluated for evidence of wound infection.
4. Count of Participants With Venous Thrombosis After Surgery During Hospitalization [ Time Frame: Up to 72 hours following surgery plus 3 weeks follow-up ]
   Evaluation of the surgical wound for symptoms of venous thrombosis was made every day during hospitalization. Records from the first post-operative clinic visit were also evaluated for evidence of venous thrombosis.
5. Assess Rates of Wound Dehiscence [ Time Frame: Up to 72 hours following surgery plus 3 weeks follow-up ]
   Evaluation of the surgical wound for symptoms of wound dehiscence was made every day during hospitalization. Records from the first post-operative clinic visit were also evaluated for evidence of wound dehiscence.
6. Total Length of Hospital Stay [ Time Frame: Up to approximately 5 days maximum (admittance to discharge) ]
   Total length of hospital stay for patients enrolled in the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

-Patients 18 years of age and older presenting to the Stanford Preoperative Evaluation Clinic prior to elective orthopedic surgical procedures or elective vascular surgical procedures not involving the abdominal aorta or carotid arteries.

Exclusion Criteria:

Patients will be excluded from participation if they have one or more of the following conditions:

1. Evidence of active local or systemic infection as demonstrated by fever, leukocytosis (white blood cell count > 11,000/ul), productive cough, new infiltrate on chest x-ray, or purulent drainage from any source
2. End-stage renal disease
3. A history of diabetic neuropathy
4. A malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the previous 5 years
5. Leukopenia (white blood cell count < 2,000/ul)
6. Thrombocytopenia (platelet count < 100,000/ul)
7. Abnormal liver function test result (aspartate aminotransferase or alanine aminotransferase level ≥1.5-fold the upper limit of normal)
8. A history or infection with tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
9. Pregnant or breastfeeding

Contacts and Locations

Locations

United States, California

Stanford Hospital and Clinics

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Robert L Lobato, MD; Stanford U

More Information

• Responsible Party: Gary Peltz, Professor of Anesthesiology, Perioperative and Pain Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT01466764
• Other Study ID Numbers: SU-10312011-8587
• First Posted: November 8, 2011
• Results First Posted: July 6, 2017
• Last Update Posted: August 9, 2017
• Last Verified: July 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Gary Peltz, Stanford University:

biomarkers

Additional relevant MeSH terms:

Inflammation; Pathologic Processes; Interleukin 1 Receptor Antagonist Protein; Antirheumatic Agents