Efficacy of Perioperative Duloxetine as a Part of Multimodal Analgesia in Laparoscopic Colorectal Cancer Surgery

Our aim will be to evaluate the efficacy of perioperative Duloxetine in decreasing acute postoperative pain after laparoscopic colorectal cancer surgery and its role in reducing postoperative morphine requirements

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Duloxetine; Drug: Placebo oral tablet

Detailed Description

Abdominal surgery is usually associated with severe; wide spread post-operative pain. The greater propensity for pain and opioid-related side effects are likely contributing factors for poor postsurgical recovery, and it often results in significant pain and slow recovery. Although Opioids are considered the analgesics of choice to treat moderate to severe pain, their use carries the risk of side effects and hyperalgesia. Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Multimodal analgesia can be achieved by combining different analgesics and different methods of administration, to provide better analgesia synergistically compared with conventional analgesia.Therefore, lower doses for each drug can be provided with fewer overall side-effects obtained from individual compounds.Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief.

Duloxetine is a serotonin-norepinephrine reuptake inhibitor commonly prescribed for the treatment of major depression and anxiety. Duloxetine also has been used in the treatment of chronic pain conditions. There several reasons why duloxetine might improve postsurgical quality of recovery. First, systemic Duloxetine seems to have perioperative analgesic effects. In addition, as a serotonin-norepinephrine reuptake inhibitor, it is possible that the drug may prevent transient emotional problems that are common during the perioperative period. Lastly, the combination of less pain and better emotional status can result in better physical independence scores after surgery.

The main objective of the current study is to examine the effect of perioperative Duloxetine on postoperative pain after laparoscopic colorectal surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mirna Ismail; Phone Number: 01064081717; Email: Mirnaismail94@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I-III
• aged 18-65 years and scheduled for laparoscopic colorectal surgery for cancer colon

Exclusion Criteria:

• unable to express their pain or patient refusal.
• allergy to the study drug
• an abnormal liver or renal function tests
• a chronic opioid abuser(> 3 mo), being on chronic gabapentin or pregabalin(> 3 mo)
• antidepressant drugs, patients with psychiatric disorders
• Pregnant females

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group (I) (D) : (Duloxetine group)	Drug: Duloxetine; Each Patient will receive oral Duloxetine capsule 60mg at the night before operation(12hrs before surgery), the 2nd dose 60 mg Duloxetine capsule 1hr before operation and 3rd dose 60mg capsule after 24hrs postoperative
Placebo Comparator: Group (II) (P): (placebo group)	Drug: Placebo oral tablet; Each patient will receive a similar looking placebo capsule in the same time schedule. The placebo capsule will be prepared by hospital pharmacy to insure that active Duloxetine capsules will be indistinguishable from the placebo capsules contained starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
morphine consumption	total morphine consumption(mg) in 48 hours if VAS score( Visual Analog Scale ) more than 3. score from 0 to 10 where 0 = no pain and 10 = the worst pain imaginable	48 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain scores	- pain scores ( theVAS score ).evaluation the pain using VAS ( Visual Analog Scale ) scored from 0 to 10 where 0 = no pain and 10 = the worst pain imaginable	48 hours postoperative
first request of analgesia	- the time of first request of analgesia (morphine) requirement postoperative	48 hours postoperative
Postoperative sedation	Postoperative sedation will be assessed using a modified observers. Assessment of alterness /sedation scale where 6= agitated to 0 = doesn't respond to deep stimulus.	48 hours postoperative
Postoperative patient satisfaction	Postoperative patient satisfaction will be measured using a numerical score of 1-4 (1= poor, 2= fair, 3= good, 4= very good) .	48 hours postoperative

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Ho KY, Tay W, Yeo MC, Liu H, Yeo SJ, Chia SL, Lo NN. Duloxetine reduces morphine requirements after knee replacement surgery. Br J Anaesth. 2010 Sep;105(3):371-6. doi: 10.1093/bja/aeq158. Epub 2010 Jun 23.
• Govil N, Parag K, Arora P, Khandelwal H, Singh A; Ruchi. Perioperative duloxetine as part of a multimodal analgesia regime reduces postoperative pain in lumbar canal stenosis surgery: a randomized, triple blind, and placebo-controlled trial. Korean J Pain. 2020 Jan 1;33(1):40-47. doi: 10.3344/kjp.2020.33.1.40.
• Takmaz O, Bastu E, Ozbasli E, Gundogan S, Karabuk E, Kocyigit M, Dede S, Naki M, Kose F, Gungor M. Perioperative Duloxetine for Pain Management After Laparoscopic Hysterectomy: A Randomized Placebo-Controlled Trial. J Minim Invasive Gynecol. 2020 Mar-Apr;27(3):665-672. doi: 10.1016/j.jmig.2019.04.028. Epub 2019 Aug 30.
• Attia JZ, Mansour HS. Perioperative Duloxetine and Etoricoxibto improve postoperative pain after lumbar Laminectomy: a randomized, double-blind, controlled study. BMC Anesthesiol. 2017 Dec 2;17(1):162. doi: 10.1186/s12871-017-0450-z.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: Duloxetine

Drug and device information, study documents

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