The Effect of Gabapentin on Thoracic Epidural Analgesia Following Thoracotomy (GABATEA)

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

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

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Gabapentin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo group	Drug: Placebo; 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
Active Comparator: Gabapentin; Gabapentin group	Drug: Gabapentin; 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); Other Names: Gabapentin "Sandoz" 300 mg

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital Skejby
• Investigators: Principal Investigator: Hans K Pilegaard, MD, Chief Surgeon, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark; Study Director: Kasper Grosen, RN, MHScS, PhDS, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark; Study Chair: Mogens P Jensen, MD, Chief Physician, PhD, Department of Reumatology, Aarhus University Hospital, Aarhus Hospital, Denmark; Study Chair: Gerhard Linnemann, MD, Chief Physician, Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Denmark; Study Chair: Vibeke Laursen, RN, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark; Study Chair: Anette Hoejsgaard, MD, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: April 27, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 5, 2010

Study Record Updates

• Last Update Posted (Estimate): August 5, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Quality of Life; Analgesia; Gabapentin; Thoracotomy; Pain, Postoperative; Recovery of Function
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: 2007-002769-11