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

• ClinicalTrials.gov Identifier: NCT00621530
• Recruitment Status: Terminated
• First Posted: February 22, 2008
• Results First Posted: July 27, 2017
• Last Update Posted: September 11, 2018
• Sponsor: Wake Forest University
• Collaborator: National Institute of General Medical Sciences (NIGMS)
• Information provided by (Responsible Party): Wake Forest University Health Sciences ( Wake Forest University )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hip Arthroplasty	Drug: ketorolac tromethamine opthalmic solution; Drug: placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Intrathecal Ketorolac on Mechanical Hypersensitivity After Total Hip Arthroplasty
• Study Start Date: March 2008
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

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: Acular- Preservative Free (PF); Ketorolac
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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Present Pain Intensity [ Time Frame: 6 months ]
   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
2. McGill Pain Intensity [ Time Frame: 6 months ]
   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.
3. McGill Affective Pain [ Time Frame: 6 months ]
   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.
4. Neuropathic Pain Symptom Inventory [ Time Frame: 6 months ]
   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.

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:

• 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

Contacts and Locations

Locations

United States, North Carolina

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

The Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44120

Sponsors and Collaborators

Wake Forest University

National Institute of General Medical Sciences (NIGMS)

Investigators

• Principal Investigator: James C. Eisenach, MD; Wake Forest University Health Sciences

  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences ( Wake Forest University ):

Study Protocol and Statistical Analysis Plan  [PDF] February 24, 2011

Informed Consent Form  [PDF] May 1, 2009

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Wake Forest University
• ClinicalTrials.gov Identifier: NCT00621530
• Other Study ID Numbers: IRB00004736; 5R37GM048085 ( U.S. NIH Grant/Contract )
• First Posted: February 22, 2008
• Results First Posted: July 27, 2017
• Last Update Posted: September 11, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences ( Wake Forest University ):

Total hip arthroplasty; Total hip replacement; Pain, postoperative; Ketorolac; Patients undergoing unilateral total hip arthroplasty

Additional relevant MeSH terms:

Hypersensitivity; Immune System Diseases; Ketorolac; Ketorolac Tromethamine; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action