Clinical trial NCT05206110: Low Dose Versus Normal Dose Ketorolac for Postoperative Pain After Prostatectomy and Hysterectomy
Official title: Low Dose Versus Normal Dose Ketorolac for Postoperative Pain After Prostatectomy and Hysterectomy: a Double-blind Randomized Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anesthesia
Surgery
Keywords: Ketolorac
Dosage
Lead sponsor: Jessa Hospital
Sponsor class: OTHER
First posted: 2022-01-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain at rest 8 hours after surgery: Numeric Rating Scale (NRS)
timeFrame: At 8 hours after surgery
Secondary outcomes:
measure: Pain at rest at PACU, 2, 4, 6, 12, 16 and 24 hours after surgery: Numeric Rating Scale (NRS)
timeFrame: At PACU, 2, 4, 6, 12, 16 and 24 hours after surgery
measure: Pain at movement at PACU, 2, 4, 6, 8, 12, 16 and 24 hours after surgery: Numeric Rating Scale
timeFrame: At PACU, 2, 4, 6, 8, 12, 16 and 24 hours after surgery
measure: Piritramide consumption at PACU (mg)
timeFrame: At PACU until 2 hours after surgery
measure: Piritramide consumption first 24 hours postoperative (mg): PCIA pump
timeFrame: First 24 hours after surgery
measure: Quality of sleep during the first postoperative night: Numeric Rating Scale
timeFrame: First postoperative night
measure: Patient satisfaction: Numeric Rating Scale
timeFrame: 1week postoperatively assessed with telephone-call
measure: Global Surgical Recovery Index
timeFrame: Before surgery (baseline) and 1 week postoperatively assessed with telephone-call
measure: EQ-5D
timeFrame: Before surgery (baseline) and 1 week postoperatively assessed with telephone-call
measure: Adverse effects of ketorolac use or suspected by the use of ketorolac
timeFrame: During study completion, i.e. 1 week after the surgery
measure: Fear of the surgical procedure: Surgical fear questionnaire
timeFrame: Before surgery (baseline)
measure: Expected pain after surgery: Numeric Rating Scale
timeFrame: Before surgery (baseline)
measure: Pain before surgery: Numeric Rating Scale
timeFrame: Before surgery (baseline)
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa hospital
state: Limburg
Study officials:
References: