Toradol v. Celecoxib for Postoperative Pain (POP)

A Randomized Control Trial Study of the Efficacy of Celecoxib Versus Ketorolac for Perioperative Pain Control

Randomized control trial between ketorolac versus celecoxib for postoperative pain following hysterectomy.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Celecoxib; Drug: Ketorolac

Detailed Description

Purpose:

To determine if Celebrex (Celecoxib) is as effective as Toradol (Ketorolac) at controlling postoperative pain when given in addition to standard postoperative pain control regimens.

Rationale:

Toradol (Ketorolac) is currently used by many surgeons as adjuvant therapy in addition to standard narcotics in managing immediate postoperative pain. Toradol (Ketorolac) is a non-steroidal anti-inflammatory drug that acts as a non-selective cyclooxygenase (COX), inhibiting COX-1 and COX-2 isoforms. (Toradol) Ketorolac has been associated with significant complications including postoperative bleeding and acute renal insufficiency. Celebrex (Celecoxib) is a selective COX-2 inhibitor that has been associated with adverse cardiovascular outcomes in patients with pre-existing cardiac disease but not with postoperative bleeding or renal insufficiency. Celebrex (Celecoxib) has also been shown to control postoperative pain but has never been compared to Toradol (Ketorolac).

Population:

Patients undergoing hysterectomy on the gynecology oncology service.

Design:

Randomized control trial.

Procedures:

All patients will receive a standard postoperative pain regimen with oral Tylenol (Acetaminophen), oral Lortab (Hydrocodone/Acetaminophen) as needed, and IV Dilaudid (Hydromorphone) as needed.

Randomization: Each participant will be assigned a number using a random number generator for assignment to one of the two postoperative pain regimens:

Arm 1:

Patients ages 18-65 will receive IV Toradol (Ketorolac) 30mg q6 hrs after their operation for 48 hrs or until hospital discharge if patients are discharged home in less than 48 hours after their operation.

**Patients over age 65 will receive IV Toradol (Ketorolac) 15mg q6hrs instead of 30mg

Arm 2:

Patients who will receive oral Celebrex (Celecoxib) 400mg 1 hour prior to their procedure then 200mg oral twice daily for a total of seven days. Patients discharged prior to 7 days will be given a prescription for Celebrex (Celecoxib) to complete a total of 7 days.

Following surgery all patients will be given a postoperative questionnaire at the day of surgery, which was returned at the two week postoperative visit, examining time until return to ADLs, days of narcotic use, and number of narcotic pills used.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist Hospital System

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients undergoing hysterectomy

Exclusion Criteria:

• Coronary Artery Disease
• Peptic Ulcer Disease
• Chronic Renal Disease
• Liver disease
• Alcohol Abuse
• Daily narcotic usage
• Narcotic use 24 hours prior to surgery
• Crohn's Disease
• History of myocardial infarction
• History of stroke
• Preoperative hematocrit less than 24
• Asthma
• Ulcerative Colitis
• Diverticulitis
• Aspirin Allergy
• Sulfonamide Allergy
• Pre-operative pain score of greater than 3
• Patients undergoing procedures that may involve bowel resection or bowel reanastomosis.
• Allergy to any non-steroidal anti-inflammatory drug
• Cardiac anomaly or disease
• Congestive Heart Failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketorolac; Patients receiving scheduled ketorolac postoperatively	Drug: Ketorolac
Experimental: Celecoxib; Patients receiving celebrex preoperative and postoperatively for 7 days	Drug: Celecoxib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Inpatient Postoperative Pain Score	Pain measured using the Visual Analog Scale, no pain (0-0.4 cm), mild pain(0.5-4.4 cm), moderate pain (4.5-7.4 cm), and severe pain (7.5-10.0 cm). Subscale scoring was not used in analysis but provided as reference for patient and nursing staff.	48 hrs following surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Inpatient Hydromorphone Use	Average inpatient hydromorphone use measured in milligrams	48 hrs following surgery
Average Inpatient Ondansetron Use	Average inpatient ondansetron use measured in milligrams	48 hrs following surgery
Total Hospital Stay	Total hospital stay from time fo admission to time of discharge measured in hours	Following surgery
Number of Participants With Perioperative Complications	Perioperative Complications measured intraoperatively and postoperatively by type	During and after surgery
Return to Activities of Daily Living	Average number of days required for complete return to independent activities of daily living	2 weeks after discharge
Days of Oral Narcotic Use After Discharge	Measured using postoperative questionnaire	2 weeks after discharge
Number of Oral Narcotic Pills Used After Discharge	Number of oral narcotic pills used after discharge until 2 week postoperative visit.	2 weeks after discharge

Collaborators and Investigators

• Sponsor: Michael Ulm, MD
• Investigators: Principal Investigator: Michael A Ulm, MD, University of Tennessee

Publications and helpful links

General Publications

• Azari L, Santoso JT, Osborne SE. Optimal pain management in total abdominal hysterectomy. Obstet Gynecol Surv. 2013 Mar;68(3):215-27. doi: 10.1097/OGX.0b013e31827f5119.
• Blanton E, Lamvu G, Patanwala I, Barron KI, Witzeman K, Tu FF, As-Sanie S. Non-opioid pain management in benign minimally invasive hysterectomy: A systematic review. Am J Obstet Gynecol. 2017 Jun;216(6):557-567. doi: 10.1016/j.ajog.2016.12.175. Epub 2016 Dec 30.
• Strom BL, Berlin JA, Kinman JL, Spitz PW, Hennessy S, Feldman H, Kimmel S, Carson JL. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA. 1996 Feb 7;275(5):376-82.
• Gong L, Thorn CF, Bertagnolli MM, Grosser T, Altman RB, Klein TE. Celecoxib pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012 Apr;22(4):310-8. doi: 10.1097/FPC.0b013e32834f94cb. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): June 30, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: April 7, 2015
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; 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; Cyclooxygenase 2 Inhibitors; Ketorolac; Celecoxib
• Other Study ID Numbers: 12-02041-FB