Oral Pregabalin Premedication for Postoperative Pain Relief

• ClinicalTrials.gov Identifier: NCT04708353
• Recruitment Status: Recruiting
• First Posted: January 13, 2021
• Last Update Posted: September 5, 2021
• Sponsor: Zagazig University
• Information provided by (Responsible Party): Asmaa Mohammed Galal El-Deen, Zagazig University

Study Description

Brief Summary:

Pain management after gynecological surgeries is essential for early mobilization of the patient, decrease postoperative complication and hospital stay. The use of opioids is associated with adverse effects such as nausea, vomiting, ileus, pruritus, sedation and respiratory depression.

Previous studies stated that pregabalin has been used to reduce pre-operative anxiety, acute postoperative pain, postoperative opioid requirements, postoperative nausea, vomiting and postoperative delirium. The most effective dose of pregabalin to relief postoperative pain with least side effect is still under trial.

In this study we will compare between two different doses of pregabalin when given as oral premedication in patients undergoing gynecological surgeries under spinal anesthesia regarding postoperative pain in order to reduce opioids consumption and subsequently avoid opioid-related adverse effects.

Condition or disease	Intervention/treatment	Phase
Gynecologic Disease	Drug: placebo capsule (vitamin c); Drug: Group pregabalin 150; Drug: Group pregabalin 300	Not Applicable

Detailed Description:

Postoperative pain, nausea and vomiting continue to be one of the most common and unpleasant complications after surgery. The traditional pain treatment with opioids alone is not adequate any more. To optimize pain treatment and postoperative outcome, new analgesics and new combination of already existing analgesics are searched for.

Pain after gynecological surgery usually severe. Uncontrolled acute post-operative pain is associated with dissatisfaction, post-operative complications and considered as a strong risk factor for development of chronic pain. An enhanced recovery pathway for gynecological surgery must include a strategy to effectively control post-operative pain and allow attainment of other Enhanced Recovery After Surgery (ERAS) targets such as early mobilization and return to oral diet whilst reducing the need for opiates.

Beyond increasing the risk of developing opioid use disorder, perioperative opioid consumption may produce undesirable side effects such as nausea, vomiting, constipation, ileus, pruritus, altered mental status, urinary retention, respiratory complications and increased length of hospital stay. While many of these side effects are frustrating to patient in the immediate postoperative period, the most dangerous effects are those that affect the respiratory system such as opioid-induced respiratory depression (ORD) which consider as a significant cause of brain damage and death in the postoperative period.

Opioid reduction strategies prove useful for decreasing total opioid dose and, in turn, their associated adverse effects. Such strategies may include adjuvant non opioid analgesics such as α-2 agonists, gabapentinoids and N-methyl-D-aspartate receptor agonists as well as local, regional or neuraxial anesthesia and modification of surgical technique where possible for operative patients.

Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter gamma-amino butyric acid. It is a α2-δ ligand that has analgesic, anticonvulsant, anxiolytic and sleep-modulating activities. Pregabalin binds potently to the α2-δ subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters including glutamate, noradrenaline, serotonin, dopamine and substance P.

Pregabalin could reduce the hyperexcitability of dorsal horn neurons induced by tissue damage; therefore it may be useful in the postsurgical pain prevention.

In 2015, a meta-analysis published in British Medical Journal (BMJ) suggested that pregabalin could improve postoperative analgesia and opioid-related adverse effects namely, vomiting and visual disturbances after surgery. However, the use of the pregabalin for acute postoperative pain is still under trial though widely reported.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The patients will be allocated randomly using computer generated randomization table into three equal groups
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: double-blinded ( patient and outcome assessors)
• Primary Purpose: Treatment
• Official Title: Effect of Two Different Doses of Oral Pregabalin Premedication for Postoperative Pain Relief After Gynecological Surgeries
• Actual Study Start Date: August 20, 2020
• Estimated Primary Completion Date: October 2021
• Estimated Study Completion Date: November 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: control group; the patient will receive one placebo capsule (vitamin c) once one hour before the operation.	Drug: placebo capsule (vitamin c); the patient will receive one placebo capsule (vitamin c) once one hour before the operation
Active Comparator: Group Pregabalin 150; the patient will receive one capsule of pregabalin 150 mg once one hour before the operation	Drug: Group pregabalin 150; the patient will receive one capsule of pregabalin 150 mg once one hour before the operation; Other Name: p150
Active Comparator: Group Pregabalin 300; the patient will receive one capsule of pregabalin 300 mg once one hour before the operation	Drug: Group pregabalin 300; the patient will receive one capsule of pregabalin 300 mg once one hour before the operation; Other Name: p300

Outcome Measures

Primary Outcome Measures :

1. changes in Postoperative pain [ Time Frame: at 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours postoperatively ]
   will be assessed by visual analogue scale (VAS), On a scale of 0-10, the patient will learn to quantify postoperative pain where 0= No pain and 10= Maximum worst pain.

Secondary Outcome Measures :

1. The level of sedation [ Time Frame: at 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours postoperatively ]

   using the modified Ramsay Sedation Score:

   1. Patient is anxious and agitated or restless, or both.
   2. Patient is cooperative, oriented and tranquil.
   3. Patient responds to commands only.
   4. Patient exhibits brisk response to light glabellar tap or loud auditory stimulus.
   5. Patient exhibits sluggish response to light glabellar tap or loud auditory stimulus.
   6. Patient exhibits no response.
2. Total amount of rescue analgesic [ Time Frame: in the first 24 hours ]
   Total amount of rescue analgesic requirement by the patient

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 60 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female patients scheduled for benign gynecological surgeries (abdominal hysterectomy, myomectomy, adnexal mass or disturbed ectopic pregnancy) under spinal anesthesia.
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Physical status: ASA I-II
• BMI ≥ 20kg/m2 & ≤ 35kg/m2,
• Written informed consent from the patient.

Exclusion Criteria:

• Patients with known history of allergy to study drugs,
• Patients on ACE inhibitors, anticonvulsant therapy or any drug interacting with pregabalin,
• Patients on chronic alcohol, opioid, tranquilizer or sedative use,
• Patient with renal impairment or heart failure,
• Pregnant females, Psychological, mental disorders or depression,
• Patients receiving anticoagulants therapy or suspected coagulopathy,
• Patients already on pregbalin or gabapentin therapy.

Contacts and Locations

Contacts

Contact: Asmaa M Galal, MD; 01271550089 ext 002; asmaa_galal79@yahoo.com

Contact: Rehab A Wahdan, MD; 01003481323 ext 002; obz13w@yahoo.com

Locations

Egypt

faculty of medicine, Zagazig university; Recruiting

Zagazig, Elsharqya, Egypt, 44519

Contact: Howaida A Kamal, MD 01225096755 ext 002 k.howaida@yahoo.com

Sponsors and Collaborators

Zagazig University

More Information

Publications:

Guay DR. Pregabalin in neuropathic pain: a more "pharmaceutically elegant" gabapentin? Am J Geriatr Pharmacother. 2005 Dec;3(4):274-87. Review.

Dahl JB, Mathiesen O, Møiniche S. 'Protective premedication': an option with gabapentin and related drugs? A review of gabapentin and pregabalin in in the treatment of post-operative pain. Acta Anaesthesiol Scand. 2004 Oct;48(9):1130-6. Review.

Mishriky BM, Waldron NH, Habib AS. Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis. Br J Anaesth. 2015 Jan;114(1):10-31. doi: 10.1093/bja/aeu293. Epub 2014 Sep 10. Review.

Balaban F, Yağar S, Özgök A, Koç M, Güllapoğlu H. A randomized, placebo-controlled study of pregabalin for postoperative pain intensity after laparoscopic cholecystectomy. J Clin Anesth. 2012 May;24(3):175-8. doi: 10.1016/j.jclinane.2011.06.027. Epub 2012 Mar 28.

• Responsible Party: Asmaa Mohammed Galal El-Deen, lecturer of anesthesia and surgical intensive care, Zagazig University
• ClinicalTrials.gov Identifier: NCT04708353
• Other Study ID Numbers: 19-11-2020
• First Posted: January 13, 2021
• Last Update Posted: September 5, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: planned after the completion of the study and publication
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code
• Time Frame: planned after the completion of the study and publication
• Access Criteria: principal investigator

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

Keywords provided by Asmaa Mohammed Galal El-Deen, Zagazig University:

Oral Pregabalin; Postoperative Pain Relief; Gynecological Surgeries

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Ascorbic Acid; Pregabalin; Vitamins; Micronutrients; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Antioxidants; Protective Agents