Low Dose Versus Normal Dose Ketorolac for Postoperative Pain After Prostatectomy and Hysterectomy

Low Dose Versus Normal Dose Ketorolac for Postoperative Pain After Prostatectomy and Hysterectomy: a Double-blind Randomized Controlled Non-inferiority Trial

A monocenter, prospective, double-blind, randomized controlled non-inferiority trial will be designed to investigate if ketorolac 10 mg is as effective for pain relief as the standard dose of 30 mg in patients undergoing robot assisted radical prostatectomy (RARP) or hysterectomy by laparoscopic assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH). It is hypothesised that the postoperative pain score at rest at 8 hours after surgery when receiving ketolorac 10 mg is non-inferior to the pain score at rest when receiving ketolorac 30mg.

Study Overview

• Status: Recruiting
• Conditions: Surgery; Anesthesia
• Intervention / Treatment: Drug: 10 mg IV ketorolac; Drug: 30 mg IV ketorolac

Detailed Description

Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), is a commonly used and effective drug for moderate to severe postoperative pain. It is widely prescribed as one of the first steps in acute and postoperative pain since decades. Because of its non-opioid character, this type of drug is safe concerning the risk of addiction and respiratory depression in the postoperative setting, but other side-effects are well known.

Gastro-intestinal (GI) haemorrhage is the most feared complication. The risk of a GI-bleeding increases with age, higher doses and longer duration of therapy. Decrease in renal function seems less important than always assumed. Feldman et al proved that developing renal failure with the use of NSAIDs was rather rare (1,1%) and similar for ketorolac as for opioids. Nonetheless, the risk again increased in a linear fashion with the duration of use. Especially for the postoperative and trauma patient, the fear of platelet inhibition and subsequent bleeding has dominated restriction of its use. Other adverse effects of ketorolac, i.e. cardiovascular toxicity, asthma, allergic reaction, etc., are usually less of a concern for the physician.

In an attempt to reduce these unwanted side effects but still have the benefit of its highly effective analgesic activity, patients should be given the lowest effective dose. Several studies have already demonstrated that ketorolac analgesic efficacy at 10 mg is similar to that at higher doses due to a ceiling effect. Unfortunately, none of the published trials investigated pain scores of the alternative dose beyond 6 hours. Based on the pharmacokinetics of ketorolac, it is possible that the lower dose will loose its analgesic effect after a shorter period. To investigate whether this alternative dose of ketorolac will preserve its analgesic efficacy up to eight hours postoperative, the primary goal of this study will be the pain score after 8 hours, right before the next dose of ketorolac.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Björn Stessel; Phone Number: 003211222107; Email: bjorn.stessel@jessazh.be
• Study Contact Backup: Name: Ina Callebaut; Phone Number: 003211339848; Email: ina.callebaut@jessazh.be

Study Locations

• Belgium
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Recruiting
      • Jessa Hospital
      • Contact: Björn Stessel, Dr.; Phone Number: 003211222107; Email: bjorn.stessel@jessazh.be
      • Contact: Ina Callebaut, PhD; Phone Number: 003211339848; Email: ina.callebaut@jessazh.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients between 18 and 70 years
• Patients undergoing RARP, LAVH or TLH
• ASA 1-3
• Scheduled as inpatient surgery (at least 1 night)
• Body weight > 60 kg

Exclusion Criteria:

• Refusal of the patient
• Cognitive impairment or no understanding of the Dutch language
• Allergy for salicylates or NSAID
• Pregnancy
• Active or history of peptic ulcer disease
• History of gastro-intestinal hemorrhage or perforation
• History of gastric bypass
• History of renal disease with creatinine > 1 mg/dl
• Haematological disease
• Tromboctopenia < 150000 / µl
• Current anticoagulant use
• Current clopidogrel use
• History of substance abuse or use of medication with a suppressive effect on the central nervous system

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: Peri- and postoperative 10 mg Ketolorac; Patients undergoing LAVH, RARP or TLH will receive dosages of 10 mg ketolorac (IV).	Drug: 10 mg IV ketorolac; Patients undergoing LAVH, RARP or TLH will receive half an hour before the end of surgery, 10 mg ketorolac (IV). Also, 10 mg IV ketorolac will be given 8h and 16h after the surgery
Active Comparator: Peri- and postoperative standard-dose 30 mg Ketolorac; Patients undergoing LAVH, RARP or TLH will receive standard dosages of 30 mg ketolorac (IV).	Drug: 30 mg IV ketorolac; Patients undergoing LAVH, RARP or TLH will receive half an hour before the end of surgery, 30 mg ketorolac (IV). Also, 30 mg ketorolac will be given 8h and 16h after the surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at rest 8 hours after surgery: Numeric Rating Scale (NRS)	Pain at rest 8 hours after surgery (measured via an 11-point Numeric Rating Scale where 0 = no pain and 10 is worst pain imaginable)	At 8 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at rest at PACU, 2, 4, 6, 12, 16 and 24 hours after surgery: Numeric Rating Scale (NRS)	Pain at rest at PACU, 2, 4, 6, 12, 16 and 24 hours after surgery (measured via an 11-point Numeric Rating Scale where 0 = no pain and 10 is worst pain imaginable)	At PACU, 2, 4, 6, 12, 16 and 24 hours after surgery
Pain at movement at PACU, 2, 4, 6, 8, 12, 16 and 24 hours after surgery: Numeric Rating Scale	Pain at movement at PACU, 2, 4, 6, 12, 16 and 24 hours after surgery (measured via an 11-point Numeric Rating Scale where 0 = no pain and 10 is worst pain imaginable)	At PACU, 2, 4, 6, 8, 12, 16 and 24 hours after surgery
Piritramide consumption at PACU (mg)	Mean total postoperative intravenous piritramide consumption at PACU (milligram)	At PACU until 2 hours after surgery
Piritramide consumption first 24 hours postoperative (mg): PCIA pump	Total amount of intravenous piritramide used in the first 24h postoperative. Use of piritramide will be objectified by a patient controlled intravenous analgesia (PCIA) pump. Information on piritramide consumption will be extracted from the PCIA-system and analyzed using 4-hour intervals.	First 24 hours after surgery
Quality of sleep during the first postoperative night: Numeric Rating Scale	Quality of sleep during the first postoperative night, as measured by an 11-point NRS (where 0 = no sleep at all, and 10 = sleeping very well)	First postoperative night
Patient satisfaction: Numeric Rating Scale	Overall patient satisfaction with pain therapy, as assessed with an 11-point NRS scale (where 0 = not satisfied at all and 10 = extremely satisfied).	1week postoperatively assessed with telephone-call
Global Surgical Recovery Index	General health status at that moment, as assessed with a scale (where 0=worst imaginable health status, and 100 = best imaginable health status)	Before surgery (baseline) and 1 week postoperatively assessed with telephone-call
EQ-5D	Quality of life concerning mobility, self-care, pain/discomfort and anxiety/depression, as assessed with a score (where 0 = lowest quality of life, and 1 = highest quality of life)	Before surgery (baseline) and 1 week postoperatively assessed with telephone-call
Adverse effects of ketorolac use or suspected by the use of ketorolac	Possible adverse effects related to ketolorac are: GI-bleeding, acute kidney failure (defined as an increase in serum creatinine by 1,5), postoperative bleeding (defined as the necessity of packed cells transfusion or surgical relook), allergic reaction and asthma exacerbation.	During study completion, i.e. 1 week after the surgery
Fear of the surgical procedure: Surgical fear questionnaire	Fear of the surgical procedure using an 8-item Surgical Fear Questionnaire.	Before surgery (baseline)
Expected pain after surgery: Numeric Rating Scale	Expected pain after surgery measured via an 11-point Numeric Rating Scale where 0 = no pain and 10 is worst pain imaginable)	Before surgery (baseline)
Pain before surgery: Numeric Rating Scale	Pain before surgery measured via an 11-point Numeric Rating Scale where 0 = no pain and 10 is worst pain imaginable)	Before surgery (baseline)

Collaborators and Investigators

• Sponsor: Jessa Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): January 25, 2022

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Dosage; Ketolorac
• 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; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: f/2021/129

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