Immunomodulation, IL-1 Inhibition, and Postoperative Incisional Pain

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Immunomodulation, IL-1 Inhibition, and Postoperative Incisional Pain

Conditions
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Pain, Inflammation

Intervention / Treatment
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* Drug: Anakinra
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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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: 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 End-stage renal disease A history of diabetic neuropathy A malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the previous 5 years Leukopenia (white blood cell count < 2,000/ul) Thrombocytopenia (platelet count < 100,000/ul) Abnormal liver function test result (aspartate aminotransferase or alanine aminotransferase level ≥1.5-fold the upper limit of normal) A history or infection with tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anakinra<br>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<br>* An injection of 100 mg Anakinra was administered 1 hour prior to surgery and again 24 hours following surgery.<br>* Other names: Kineret;|
| Placebo Comparator: Saline injection<br>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<br>* An injection of normal saline was administered 1 hour prior to surgery and again 24 hours following surgery.<br>* Other names: No other name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration Levels of Inflammatory Mediators IL-1 Receptor Antagonist (IL-1ra) Present in Human Wounds Following Surgery With and Without the Use of Anakinra. | 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 | Up to 72 hours following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Analgesic Consumption During the 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 | Up to 72 hours following surgery | 
| Post-operative Pain Intensity | 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) | Up to 72 hours following surgery | 
| Count of Participants Experiencing Wound Infection in the Study From Surgery Till the Time of Discharge From the Hospital | 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. | Up to 72 hours following surgery plus 3 weeks follow-up | 
| Count of Participants With Venous Thrombosis After Surgery During Hospitalization | 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. | Up to 72 hours following surgery plus 3 weeks follow-up | 
| Assess Rates of Wound Dehiscence | 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. | Up to 72 hours following surgery plus 3 weeks follow-up | 
| Total Length of Hospital Stay | Total length of hospital stay for patients enrolled in the study. | Up to approximately 5 days maximum (admittance to discharge) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarkers