Effectiveness, cost-effectiveness and safety of gabapentin versus placebo as an adjunct to multimodal pain regimens in surgical patients: protocol of a placebo controlled randomised controlled trial with blinding (GAP study)

Abstract

IntroductionGabapentin is an antiepileptic drug currently licensed to treat epilepsy and neuropathic pain but has been used off-label to treat acute postoperative pain. The GAP study will compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain after major surgery.Methods and analysisThe GAP study is a multicentre, double-blind, randomised controlled trial in patients aged 18 years and over, undergoing different types of major surgery (cardiac, thoracic or abdominal). Patients will be randomised in a 1:1 ratio to receive either gabapentin (600 mg just before surgery and 600 mg/day for 2 days after surgery) or placebo in addition to usual pain management for each type of surgery. Patients will be followed up daily until hospital discharge and then at 4 weeks and 4 months after surgery. The primary outcome is length of hospital stay following surgery. Secondary outcomes include pain, total opioid use, adverse health events, health related quality of life and costs.Ethics and disseminationThis study has been approved by the Research Ethics Committee . Findings will be shared with participating hospitals and disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and participant newsletters.Trial registration numberISRCTN63614165.

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

“…Hence, gabapentinoids remain a valuable tool in the perioperative opioid stewardship arsenal for appropriate patients and are supported by multiple guidelines [15,18,197,201]. Ongoing controlled trials may further delineate the effectiveness, safety, and cost-effectiveness of perioperative gabapentinoids [202]. Some pharmacokinetic differences exist between gabapentin and pregabalin, though both are heavily renally eliminated.…”

Gabapentin Increases Intra-Epidermal and Peptidergic Nerve Fibers Density and Alleviates Allodynia and Thermal Hyperalgesia in a Mouse Model of Acute Taxol-Induced Peripheral Neuropathy

“…Taxol-induced persistent mechanical allodynia was measured up to three weeks after the 1st Taxol injection ( Figure 2 B). Gabapentin was administered i.p., at a dose of 150 mg/kg, beginning 24 h after the last Taxol injection ( Figure 1 , 2nd and 3rd week, therapeutic effect), at a cumulative dose of 900 mg/kg, that is, in the range of the doses used to treat chemotherapy-induced, peripheral neuropathy in mice [ 16 , 18 ], reported efficacious for the management of pain in patients [ 40 , 41 , 42 ], and lower than the maximally tolerated dose in mice of 2000 mg/kg/day [ 43 ]. At baseline (day-1, Figure 2 B), there were no significant differences between the healthy, disease-vehicle-treated, and disease-gabapentin-treated mice groups.…”

Informed Consent for Placebo‐Controlled Trials: Do Ethics and Science Conflict?

“…29 In the GAP study, the placebo is presented in consent documents as a "dummy pill. " 30 Yet, as discussed previously, placebo and nocebo effects can have important effects on pain. Bioethicists contend that omission of information about placebo and nocebo effects violates the requirement to adequately disclose known risks and benefits and is therefore unethical.…”

“…Materials about the study were provided courtesy of Sarah C. Baos, of the Bristol Population Health Science Institute's Clinical Trials Evaluation Unit. 27 The GAP study is designed "to compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain following three types of major surgery (cardiac, thoracic and abdominal). " This is a multicentered, parallel-group, pragmatic randomized trial in the United Kingdom.…”

“…The Gabapentin in Post Surgery Pain (GAP) Study (ISRCTN registry trial number ISRCTN63614165) allows us to illustrate the conflict between science and ethics that has the potential to arise as researchers seek individuals’ consent to participate in a clinical trial. Materials about the study were provided courtesy of Sarah C. Baos, of the Bristol Population Health Science Institute's Clinical Trials Evaluation Unit 27 …”