Effect of Spinal Ketorolac on Mechanical Hypersensitivity After a Total Hip Replacement

Effect of Intrathecal Ketorolac on Mechanical Hypersensitivity After Total Hip Arthroplasty

Chronic pain in patients following total hip replacement seems to be a significant problem. Previous research has shown that more effective pain management in the early postoperative period may decrease the incidence of the development of chronic pain states.

This study will evaluate whether ketorolac (a non steroidal anti-inflammatory drug) given into the spinal fluid before surgery will reduce the area of sensitivity (or pain to light touch) following surgery. Patients will be monitored during their postoperative hospital stay and then contacted by telephone at 8 weeks and 6 months after surgery and questioned about any pain they are having at their surgical site. Patients that are still experiencing pain at 6 months will be asked to return to the medical center for the study staff to assess their pain or sensitivity at the surgical site.

Study Overview

• Status: Terminated
• Conditions: Hip Arthroplasty
• Intervention / Treatment: Drug: ketorolac tromethamine opthalmic solution; Drug: placebo

Detailed Description

Surgery results in hypersensitivity to mechanical stimuli surrounding the wound and in a subset of patients, also results in chronic pain. The purpose of the study is to test whether intrathecal ketorolac, by selectively and effectively blocking cyclooxygenase in the spinal cord, will reduce hypersensitivity surrounding the surgical wound in patients with high risk for developing chronic pain after surgery. We have chosen to study patients having total hip arthroplasty (THA) because chronic pain seems to be a significant problem after surgery. We will sample cerebrospinal fluid (CSF) prior to injection of the study medication for subsequent prostaglandin E2 (PGE2) analysis in each patient. We will also assess each patient at 48 hours after their surgery for hypersensitivity at their surgical site.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44120
      • The Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physical status I, II, III
• > Age 18
• Primary unilateral total hip arthroplasty under spinal anesthesia

Exclusion Criteria:

• Known allergy to study medication
• Weight > 300 pounds
• Obstructive sleep apnea
• Patients with severe renal (kidney) or hepatic (liver) disease, allergy to ketorolac, amino amide local anesthetic, or contraindications to spinal anesthesia
• Patients on dialysis for kidney failure or patients that are jaundice or have a diagnosis of liver failure
• Patients routinely taking narcotic pain medications for pain other than their primary hip pain
• Patients that are taking Lyrica (pregabalin) or Gabapentin (neurontin) for the treatment of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketorolac; ketorolac 2 mg ketorolac tromethamine opthalmic solution	Drug: ketorolac tromethamine opthalmic solution; ketorolac 2 mg will be added to the patient's routine spinal anesthetic for surgery; Other Names: Ketorolac; Acular- Preservative Free (PF)
Placebo Comparator: Placebo; placebo will be added to the patient's routine spinal anesthetic for surgery	Drug: placebo; placebo will be added to the patient's routine spinal anesthetic for surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area of Hypersensitivity to Mechanical Stimuli Surrounding the Wound 48 Hours After Surgery	Hyperalgesia (using a von Frey filament) and allodynia (using a cotton swab) were evaluated around the surgical site 48 hours after surgery.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Present Pain Intensity	Pain was assessed preoperatively, 2 days, and 2 and 6 months after surgery using a 0-10 (10 being worse) verbal Present Pain Intensity (PPI) scale	6 months
McGill Pain Intensity	Pain was assessed 2 days and 2 and 6 months after surgery using a validated questionnaire wherein subjects rate the degree to which adjectives describe the intensity of their pain experience. This is termed the McGill Pain Intensity Score and is scored from 0 to 33 with 33 being the highest pain intensity.	6 months
McGill Affective Pain	Pain was assessed 2 days, and 2 and 6 months after surgery using a validated questionnaire wherein subjects rate the degree to which adjectives describe the emotional component of their pain experience. This is termed the McGill Pain Affective Score and is scored from 0 to 12 with 12 being the highest pain emotional impact.	6 months
Neuropathic Pain Symptom Inventory	Pain was assessed 2 days, and 2 and 6 months after surgery using a validated questionnaire to assess the degree of neuropathic characteristics of pain. This is termed the Neuropathic Pain Symptom Inventory which is scored 0-100 with 100 being the worst possible pain.	6 months

Collaborators and Investigators

• Sponsor: Wake Forest University
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: James C. Eisenach, MD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Wang L, Bauer M, Curry R, Larsson A, Sessler DI, Eisenach JC. Intrathecal ketorolac does not improve acute or chronic pain after hip arthroplasty: a randomized controlled trial. J Anesth. 2014 Oct;28(5):790-3. doi: 10.1007/s00540-014-1798-6. Epub 2014 Feb 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: February 11, 2008
• First Submitted That Met QC Criteria: February 11, 2008
• First Posted (Estimate): February 22, 2008

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Total hip arthroplasty; Pain, postoperative; Ketorolac; Total hip replacement; Patients undergoing unilateral total hip arthroplasty
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: IRB00004736; 5R37GM048085 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No