Adding Amantadine to Pregabalin on Occurrence of Post-thoracotomy Pain Syndrome

Effectiveness of Adding Amantadine to Pregabalin on Occurrence of Post-thoracotomy Pain Syndrome; Randomized Controlled Study

This study aims to evaluate the additive effect of Amantadine to Pregabaline in the development of post-thoracotomy pain syndrome.

Study Overview

• Status: Completed
• Conditions: Pregabalin; Post-thoracotomy Pain Syndrome; Amantadine
• Intervention / Treatment: Drug: Amantadine+ Pregabalin; Drug: Pregabalin

Detailed Description

Lung cancer is still the most common cause of cancer-related deaths, and lung resection surgeries could be the primary therapeutic option. Hence, the number of thoracotomy procedures is progressively increasing, as well as the development of post-thoracotomy pain syndrome (PTPS).

Pregabalin is one of the drugs that can reduce the excitability of the dorsal horn neurons. It is a γ-aminobutyric acid analogue that binds to α2-δ subunits of the voltage-gated calcium channels in the central nervous system.

Amantadine (1-aminoadamantane) is NMDA receptor antagonists. NMDA receptors were found to have role in the development of central sensitization, acute opioid tolerance, and opioid induced hyperalgesia.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt, 12613
      • Cairo university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age (18-65) years.
• Both sexes.
• American Society of Anesthesiologists (ASA) Physical status II, III.
• Body mass index (BMI): (20-40) kg/m2.
• Cancer patients undergoing posterolateral thoracotomy incision for cancer lung, mesothelioma or other lung resection procedures.

Exclusion Criteria:

• Patients with known sensitivity or contraindication to drug used in the study.
• History of psychological disorders and/or chronic pain and drug abuse patients.
• Previous administration of antidepressants, anticonvulsants, or opioids before surgery.
• Patient refusal.
• Severe respiratory or cardiac disorders.
• Advanced liver or kidney disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amantadine group; Two hours preoperative, patient will receive two capsules, one of them is Amantadine (Amantadine Hydrochloride) 100 mg and the other is Pregabalin (Lyrica) 75 mg and continued on both of them twice daily for 5 days postoperative.	Drug: Amantadine+ Pregabalin; Two hours preoperative, patient will receive two capsules, one of them is Amantadine (Amantadine Hydrochloride) 100 mg and the other is Pregabalin (Lyrica) 75 mg and continued on both of them twice daily for 5 days postoperative.
Placebo Comparator: Placebo group; Two hours preoperative, the patient will receive two capsules, one of them is pregabalin 75 mg, and the other is a placebo capsule similar to the amantadine capsule and continued on both of them twice daily for 5 days postoperative.	Drug: Pregabalin; Two hours preoperative, the patient will receive two capsules, one of them is pregabalin 75 mg, and the other is a placebo capsule similar to the amantadine capsule and continued on both of them twice daily for 5 days postoperative.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of occurrence of post-thoracotomy pain syndrome	Incidence of occurrence of post-thoracotomy pain syndrome at 12 weeks through according to grading system for neuropathic pain (GSNP). GSNP is as follows: Grade 1 (unlikely), Grade 2 (possible), Grade 3 (probable), and Grade 4 (definite), the patients will be considered positive regarding incidence being in grade 3 or 4.	12 weeks postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Quality of life	Patient's Quality of life according to Flanagan Quality of Life Scale (QOLS) which is a 16-item (domain) questionnaire with each item scored from 1 to 7 points. Participants respond to the questions using a seven-point Likert scale, ranging from 1 ("completely dissatisfied") to 7 ("delighted"). The scale will be explained to the patients and the total score will be calculated and recorded at the preoperative assessment (baseline) and at postoperative weeks 2, 4, 8, and 12.	12 weeks postoperatively
Patient's activity level	Postoperative Patient's activity level according to Barthel Activities of Daily Living scale (ADL). This scale comprises 10 basic daily activities (bowel, bladder, feeding, toilet, bathing, dressing, grooming, walking, stairs and transfer) with each item scored as 0 = need complete help, 1 = need some help or 2 = need no help	12 weeks postoperatively
Total amount of morphine consumption	Rescue analgesia will be provided in the form of intravenous morphine 3 mg boluses if the patient indicates Visual Analogue Scale (VAS) ≥ 4.	48 hours postoperatively
Total amount of fentanyl consumption	Rescue analgesia of fentanyl 1 μg/kg will be given if the mean arterial blood pressure or heart rate rises above 20% of baseline levels.	Intraoperatively
Patient Global Impression of Change (PGIC)	Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. 0 (very much worse" to 7 (very much improved).	12 weeks postoperatively
Incidence of side effects of Pregabalin	Side effects of Pregabalin such as headaches, feeling sleepy, tired or dizzy, diarrhoea, mood changes, feeling sick, swollen hands, arms, legs and feet, blurred vision, difficulties with getting an erection, and weight gain - because pregabalin can cause you feel hungry, and memory problems will be recorded.	12 weeks postoperatively
Incidence of side effects of Pregabalin	The side effects of Amantadine such as dry mouth, constipation, nausea, vomiting, decreased appetite, difficulty falling asleep or staying asleep, abnormal dreams, headache, confusion, drowsiness, tiredness, uncontrollable tightening of muscles, change from normal walking to falls, and a lace-like purple pattern on the skin.	12 weeks postoperatively

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Somatoform Disorders; Syndrome; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin
• Other Study ID Numbers: AP2310-201-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be available upon a reasonable request from the corresponding author after the end of study for one year.
• IPD Sharing Time Frame: After the end of study for one year.
• IPD Sharing Access Criteria: The data will be available upon a reasonable request from the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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