Oral Pregabalin as Preemptive Analgesia in Abdominal Hysterectomy

NCT04495374 | Terminated Phase 4 Results DMC

• 1 other identifier: 3.334.050
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Postoperative pain affects 80% of surgical patients and is one of the main negative symptoms resulting from surgery. It impairs the recovery of patient since it is related to chronic pain, nausea and vomiting and longer hospital stay, generating higher cost to the health system. Thus, the use of new methods to control postoperative pain is recommended and multimodal analgesia, an opioid-sparing strategies, has been widely used by several researchers. Studies show that gabapentins have beneficial effects on postoperative pain control when used as pre-anesthetic medication, also showing a reduction in opioid consumption, with few adverse effects. Among gynecological surgeries, abdominal hysterectomy is one of the procedures that generates the highest degree of acute postoperative pain. Thus, the aim of the present study is to investigate the effect of oral pregabalin (300 mg) two hours before abdominal hysterectomy procedures on postoperative pain. This study is a randomized, double-blind, placebo controlled clinical trial. Patients submitted to abdominal hysterectomy for benign pathologies will be selected and divided into two groups: the placebo controlled group (P0) and the pregabalin 300 mg group (P1). Group P0 will receive a placebo tablet one hour before the procedure, while group P1 will receive a 300 mg tablet of pregabalin identical to the placebo tablet. The reduction of postoperative pain and the best quality of patient recovery will be evaluated using the Visual Analogue Pain Scale (VAS) and the McGill Pain Questionnaire. Also, it will be evaluated the consumption of opioids as a rescue analgesic medication and the presence of adverse effects such as nausea and vomiting.

Conditions

Pain, Postoperative; Analgesia; Gabapentin Adverse Reaction; Opioid Abuse

Keywords

postoperative pain; multimodal analgesia; pregabalin; preemptive analgesia; abdominal hysterectomy; gabapentins

Outcome Measures

Primary Outcomes (3)

• Postoperative Pain in Rest Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)

  Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.

  End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)

• Postoperative Pain Assessed 24 Hours After Abdominal Hysterectomy Surgery, Using the McGill Pain Questionnaire

  Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single 300mg dose of pregabalin or placebo as preemptive analgesia, using the McGill pain questionnaire, which consists of 20 word groups , and each group can contain from 2 to 6 descriptive words, these descriptors are placed in an increasing order of magnitude in relation to the intensity. The left of each word has a numerical value in an attempt to represent the intensity of the descriptor. For the analysis of the answers, the total number of words chosen in each subgroup by the patient was used to qualify his pain, the minimum value being equal to 0 (zero), if the patient chose not to choose any descriptor, and the maximum value would be 20, as the patient can choose only one descriptor for each subgroup. The quantitative pain index was also evaluated, which represents the sum of the values of each descriptor chosen by the patient, with a minimum value of 0 and a maximum of 78.

  End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)

• Postoperative Pain in Active Movement Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)

  Postoperative pain assessment, 24 hours after abdominal hysterectomy surgery, in patients who used a single dose of pregabalin 300mg or placebo as preemptive analgesia, using the visual analog scale (VAS) consisting of a 10 cm (cm) line ) graduated in natural number intervals, starting at 0 (zero) until reaching 10 (ten), associated with the numbers, drawings related to the pain presented by the patient at the moment, in which the absence of pain (0 ) there is a happy face, and as the numerical value increases, the drawn face will represent the intensity of pain, up to the value of 10, where a face with crying characteristics is found, indicating greater pain.

  End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)

Secondary Outcomes (3)

• Number of Doses of Opioids Used as Analgesic Rescue in the Postoperative Period

  End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)

• Time Required for the Use of the First Dose of Opioid as an Analgesic Rescue in the Postoperative Period

  End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)

• Number of Participants With Dizziness Between the Intervention and Control Groups

  End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery) and also immediately in the post-anesthetic recovery room

Study Arms (2)

Group P(0) - Placebo

PLACEBO COMPARATOR

Patients were randomly allocated to Group P(0) - Placebo by a double blind randomized study. Group P(0) received two placebo tablets as medication, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B

Other: Placebo

Group P(1) - Pregabalin 300mg

EXPERIMENTAL

Patients were randomly allocated to Group P(1) - Pregabalin 300mg by a double blind randomized study. Group P(1) received two tablets of pregabalin 150mg, 02h before the start of the anesthesic-surgical procedure in identical sealed envelops, only identified as medication A or B

Drug: Pregabalin 300mg

Interventions

Pregabalin 300mg DRUG

Group P1 will receive a 300 mg tablet of pregabalin, 02h before the surgical procedure

Also known as: Preemptive analgesia

Group P(1) - Pregabalin 300mg

Placebo OTHER

Group P0 will receive a placebo tablet, 02h before the surgical procedure

Also known as: Controls

Group P(0) - Placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Gender Eligibility Details: Female patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who will undergo elective abdominal hysterectomy surgery due to benign pathologies;
• Be classified as physical status by the Society of Anesthesiologists (ASA) as ASA I (healthy individual) or ASA II (patient with mild and controlled systemic disease);

You may not qualify if:

• Allergy or intolerance previously known to pregabalin or opioids;
• Patients with chronic pain or fibromyalgia;
• Patients on chronic opioid use;
• Carriers of malignant neoplasms;
• Pregnant women;
• People with active uncontrolled cardiovascular disease;
• Patients with kidney and / or liver disease;
• Patients who have spinal deformities that make spinal anesthesia impossible;
• Presence of coagulation disorders or anticoagulant therapy that cannot be suspended for surgery;
• Presence of active sepsis.

Sponsors & Collaborators

• Universidade Federal de Alfenas: lead

Study Sites (1)

Universidade Federal de Alfenas

Alfenas, Minas Gerais, 37130-001, Brazil

Location

Related Publications (10)

• Hu J, Huang D, Li M, Wu C, Zhang J. Effects of a single dose of preoperative pregabalin and gabapentin for acute postoperative pain: a network meta-analysis of randomized controlled trials. J Pain Res. 2018 Nov 2;11:2633-2643. doi: 10.2147/JPR.S170810. eCollection 2018.

  PMID: 30519075 BACKGROUND

• As-Sanie S, Till SR, Mowers EL, Lim CS, Skinner BD, Fritsch L, Tsodikov A, Dalton VK, Clauw DJ, Brummett CM. Opioid Prescribing Patterns, Patient Use, and Postoperative Pain After Hysterectomy for Benign Indications. Obstet Gynecol. 2017 Dec;130(6):1261-1268. doi: 10.1097/AOG.0000000000002344.

  PMID: 29112660 BACKGROUND

• Farzi F, Naderi Nabi B, Mirmansouri A, Fakoor F, Atrkar Roshan Z, Biazar G, Zarei T. Postoperative Pain After Abdominal Hysterectomy: A Randomized, Double-Blind, Controlled Trial Comparing the Effects of Tramadol and Gabapentin as Premedication. Anesth Pain Med. 2016 Jan 17;6(1):e32360. doi: 10.5812/aapm.32360. eCollection 2016 Feb.

  PMID: 27110531 BACKGROUND

• Ghai A, Gupta M, Hooda S, Singla D, Wadhera R. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth. 2011 Jul;5(3):252-7. doi: 10.4103/1658-354X.84097.

  PMID: 21957402 BACKGROUND

• Kohli M, Murali T, Gupta R, Khan P, Bogra J. Optimization of subarachanoid block by oral pregabalin for hysterectomy. J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):101-5.

  PMID: 21804717 BACKGROUND

• Main CJ. Pain assessment in context: a state of the science review of the McGill pain questionnaire 40 years on. Pain. 2016 Jul;157(7):1387-1399. doi: 10.1097/j.pain.0000000000000457.

  PMID: 26713423 BACKGROUND

• Steinberg AC, Schimpf MO, White AB, Mathews C, Ellington DR, Jeppson P, Crisp C, Aschkenazi SO, Mamik MM, Balk EM, Murphy M. Preemptive analgesia for postoperative hysterectomy pain control: systematic review and clinical practice guidelines. Am J Obstet Gynecol. 2017 Sep;217(3):303-313.e6. doi: 10.1016/j.ajog.2017.03.013. Epub 2017 Mar 27.

  PMID: 28351670 BACKGROUND

• Tulandi T, Krishnamurthy S, Mansour F, Suarthana E, Al-Malki G, Ballesteros LER, Moore A. A Triple-Blind Randomized Trial of Preemptive Use of Gabapentin Before Laparoscopic Hysterectomy for Benign Gynaecologic Conditions. J Obstet Gynaecol Can. 2019 Sep;41(9):1282-1288. doi: 10.1016/j.jogc.2018.11.019. Epub 2019 Jan 25.

  PMID: 30686609 BACKGROUND

• Verret M, Lauzier F, Zarychanski R, Savard X, Cossi MJ, Pinard AM, Leblanc G, Turgeon AF. Perioperative use of gabapentinoids for the management of postoperative acute pain: protocol of a systematic review and meta-analysis. Syst Rev. 2019 Jan 16;8(1):24. doi: 10.1186/s13643-018-0906-3.

  PMID: 30651123 BACKGROUND

• Yucel A, Ozturk E, Aydogan MS, Durmus M, Colak C, Ersoy MO. Effects of 2 different doses of pregabalin on morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind clinical trial. Curr Ther Res Clin Exp. 2011 Aug;72(4):173-83. doi: 10.1016/j.curtheres.2011.06.004.

  PMID: 24648587 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Agnosia; Opioid-Related Disorders

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Failure to monitor patients 24 hours after surgery to assess parameters such as chronic pain and home opioid consumption. All patients admitted to the study underwent abdominal hysterectomy, a surgery known to have higher pain rates, which makes it impossible for the results found to be used as a basis for patients undergoing laparoscopic hysterectomy or other types of surgery.

Results Point of Contact

• Title: Profa. Dra. Larissa Helena Lobos Torres Pacheco
• Organization: Universidade Federal de Alfenas

larissa.torres@unifal-mg.edu.br

3537011805

Study Officials

• Larissa H Torres, PhD

  Universidade Federal de Alfenas

  PRINCIPAL INVESTIGATOR

• Fabrício G Silva, BSc

  Santa Casa de Alfenas

  STUDY CHAIR

• Carlos M de Barros, BSc

  Universidade Federal de Alfenas

  STUDY CHAIR

• Marcia H Podestá, PhD

  Universidade Federal de Alfenas

  STUDY CHAIR

• Carla S Ceron, PhD

  Universidade Federal de Alfenas

  STUDY CHAIR

• Thayná C Silva, BSc

  Santa Casa de Alfenas

  STUDY CHAIR

• Denismar A Nogueira, PhD

  Universidade Federal de Alfenas

  STUDY CHAIR

• Tiago M Reis, PhD

  Universidade Federal de Alfenas

  STUDY CHAIR

• Milena C Espósito, PhD

  Universidade Federal de Alfenas

  STUDY CHAIR

• Danielle A Oliveira, BSc

  Universidade Federal de Alfenas

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: July 31, 2020
• Study Start: September 2, 2019
• Primary Completion: September 9, 2020
• Study Completion: September 30, 2020
• Last Updated: March 4, 2021
• Results First Posted: March 4, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)