The Effect of Gabapentin on Thoracic Epidural Analgesia Following Thoracotomy

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to investigate the effect of gabapentin on thoracic epidural analgesia following thoracotomy, including assessment of both analgesia, pain intensity, pain quality and whether or not gabapentin prevents the development of chronic pain conditions following thoracotomy. The main hypothesis is that gabapentin reduces the proportion of patients who develop a persistent pain condition following thoracotomy from 50% to 20%. Furthermore gabapentin is expected to reduce both pain intensity measured on a 11-point numerical rating scale, usage of epidural infusions of local and/or opioid analgesics, morbidity, hospital length of stay, consumption of opioid analgesics and analgesia-related side-effects. In addition gabapentin is expected to improve postoperative recovery by means of postoperative lung function, walking ability, health related quality of life and patient satisfaction

Official Title
-----------------
The Effect of Gabapentin on Thoracic Epidural Analgesia Following Thoracotomy - A Randomized, Double-blind, Placebo-controlled Trial

Conditions
-----------------
Pain, Postoperative

Intervention / Treatment
-----------------
* Drug: Gabapentin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Elective lung resection via thoracotomy Age > 18 and < 80 years Exclusion Criteria: Inability to answer the detailed questionnaires on pain and quality of life Psychiatric disease (ICD-10) Severe renal impairment (se-creatinin > 110 mmol/l) Known allergy to gabapentin, morphine, bupivacaine and / or ibuprofen Standard use of opioid analgesics Treatment with anticonvulsants or tricyclic antidepressants Use of antacids 24 hours before the intake of study medication Contraindicated placement of a thoracic epidural catheter Previous ipsilateral thoracotomy Presence of a chronic pain syndrome Acute pancreatitis A history of past or current alcohol and / or illegal substance abuse. A history of gastric or duodenal ulcer Gastrointestinal obstruction Pregnancy Participation in another intervention study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gabapentin<br>Gabapentin group | Drug: Gabapentin<br>* Preoperatively (2 hours before surgery): 4 gabapentin capsules each containing 300 mg gabapentin (total gabapentin dose 1200 mg) Postoperative day 1: gabapentin 300 mg x 2 (total gabapentin dose 600 mg) Postoperative day 2: gabapentin 300 mg x 3 (total gabapentin dose 900 mg) Postoperative day 3: gabapentin 300 mg x 4 (total gabapentin dose 1200 mg) Postoperative day 4: gabapentin 300 mg x 4 (total gabapentin dose 1200 mg) Postoperative day 5: gabapentin 300 mg x 4 (total gabapentin dose 1200 mg)<br>* Other names: Gabapentin Sandoz 300 mg;|
| Placebo Comparator: Placebo<br>Placebo group | Drug: Placebo<br>* Preoperatively (2 hours before surgery): 4 placebo capsules Postoperative day 1: 1 placebo capsule x 2 Postoperative day 2: 1 placebo capsule x 3 Postoperative day 3: 1 placebo capsule x 4 Postoperative day 4: 1 placebo capsule x 4 Postoperative day 5: 1 placebo capsule x 4<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent post surgical pain | Pain is assessed by means of the Brief Pain Inventory (BPI-SF) and The McGill Pain Questionnaire (SF-MPQ). Persistent postoperative pain is measured both on a 11-point numeric pain rating scale and on a 10 cm visual analog scale (VAS). A score >=3 is considered as moderate pain. | 3 months after surgery | 
| Acute postoperative pain | Acute postoperative pain is measured on a 11-point numeric rating scale both at rest and when coughing/sitting up. General pain intensity and specific (shoulder) pain intensity are measured. On postoperative day 4 pain is furthermore assessed by means of the Brief Pain Inventory (BPI-SF) and The McGill Pain Questionnaire (SF-MPQ). A score >=3 is considered as moderate pain. | Within the first 5 postoperative days | 
| Usage of epidural infusion of local and opioid analgesics (ml) |  | Within the first 5 postoperative days | 
| Persistent post surgical pain | Pain is assessed by means of the Brief Pain Inventory (BPI-SF) and The McGill Pain Questionnaire (SF-MPQ). Persistent postoperative pain is measured both on a 11-point numeric pain rating scale and on a 10 cm visual analog scale (VAS). A score >=3 is considered as moderate pain. | 6 months following surgery | 
| Persistent post surgical pain | Pain is assessed by means of the Brief Pain Inventory (BPI-SF) and The McGill Pain Questionnaire (SF-MPQ). Persistent postoperative pain is measured both on a 11-point numeric pain rating scale and on a 10 cm visual analog scale (VAS). A score >=3 is considered as moderate pain. | 12 months following surgery | 
| Early postoperative pain | Early postoperative pain is measured on day 14 (+/-3 days) following discharge pain using the Brief Pain Inventory (BPI-SF) and The McGill Pain Questionnaire (SF-MPQ). A score >=3 is considered as moderate pain. | 14 days (+/-3 days) following discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consumption of opioid analgesics |  | Within the first 5 postoperative days | 
| Time to first request for additional analgesics |  | Within the first 5 postoperative days | 
| Analgesia related side-effects | Evaluation of the presence and/or severity of confusion, hallucinations, nausea, vomiting, usage of antiemetic drugs, urinary retention, sedation, pruitus, headache, respiratory depression, motor blockade and dizziness | Within the first 5 postoperative days | 
| Convalescence of gastrointestinal function | Convalescence of gastrointestinal function (time to first defecation) | Within the first 5 postoperative days | 
| Health related quality of life | Health related quality of life is measured with the EORCT QLQ-C30 and EORCT QLQ-LC13 questionnaires. | Day 14 (+/-3 days) following discharge | 
| Patient satisfaction | Patient satisfaction is assesed with the EORCT-INPATSAT32 questionnaire | Within the first 5 postoperative days | 
| Intensity of preoperative anxiety | Anxiety is measured on a 11-point numeric rating scale (NRS). | 2 hours after administration of the first dose of study medication | 
| Convalescence of lung function (spirometry) | FVC, FEV-1 and PEF is measured. | Within the first five postoperative days | 
| Sleep quality | Sleep quality is measured on a 11-point numeric rating scale (NRS) | Within the first five postoperative days | 
| Walking distance (meters) | Ability to walk is measured by means of the 6-minutes walking test on postoperative day 3. | Postoperative day 3 | 
| Fatigue | Fatigue is measured on a 4-point verbal rating scale (0=None, 1=Mild, 2=Moderate, 3=Severe). | Within the first 5 postoperative days | 
| Hospital length of stay (days) |  | At time of discharge | 
| Health related quality of life | Health related quality of life is measured with the EORCT QLQ-C30 and EORCT QLQ-LC13 questionnaires. | 3 months following surgery | 
| Health related quality of life | Health related quality of life is measured with the EORCT QLQ-C30 and EORCT QLQ-LC13 questionnaires. | 6 months following surgery | 
| Health related quality of life | Health related quality of life is measured with the EORCT QLQ-C30 and EORCT QLQ-LC13 questionnaires. | 12 months following surgery | 
| Use of a vasopressor agent to correct hypotension |  | Within the first 5 days of surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gabapentin, Thoracotomy, Pain, Postoperative, Analgesia, Recovery of Function, Quality of Life