Clinical Trial of Gabapentin to Improve Postoperative Pain in Surgical Patients
Overview[ - collapse ][ - ]
| Purpose | This will be a double blind, placebo-controlled study of patients ≥65 years of age undergoing surgery of the spine, hips and knees replacement at the University of California, San Francisco (UCSF) Medical Center. Intraoperative anesthetic and postoperative pain management will be standardized. Patients will be randomized to receive either placebo or gabapentin preoperatively, and continued postoperatively until discharge. Intraoperative anesthetic and other postoperative pain management strategies will be standardized. Postoperative delirium will be measured using structured interviews. Cognitive function will be measured using a battery of neurocognitive tests pre- and post-operatively. Using an intention to treat strategy, we, the researchers at UCSF, will compare the amount of postoperative pain, narcotic requirements, and postoperative delirium and cognitive dysfunction between the two groups. |
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| Condition | Postoperative Pain |
| Intervention | Drug: Gabapentin |
| Phase | Phase 3 |
| Sponsor | University of California, San Francisco |
| Responsible Party | University of California, San Francisco |
| ClinicalTrials.gov Identifier | NCT00221338 |
| First Received | September 19, 2005 |
| Last Updated | January 14, 2014 |
| Last verified | January 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 19, 2005 |
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| Last Updated Date | January 14, 2014 |
| Start Date | August 2005 |
| Estimated Primary Completion Date | September 2015 |
| Current Primary Outcome Measures | Postoperative delirium and cognitive decline [Time Frame: postoperative days 1, 2 and 3] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Postoperative opioid doses and pain scores [Time Frame: postoperative days 1, 2 and 3] [Designated as safety issue: Yes] |
Descriptive Information[ + expand ][ + ]
| Brief Title | Clinical Trial of Gabapentin to Improve Postoperative Pain in Surgical Patients |
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| Official Title | Clinical Trial of Gabapentin to Improve Postoperative Pain in Surgical Patients |
| Brief Summary | This will be a double blind, placebo-controlled study of patients ≥65 years of age undergoing surgery of the spine, hips and knees replacement at the University of California, San Francisco (UCSF) Medical Center. Intraoperative anesthetic and postoperative pain management will be standardized. Patients will be randomized to receive either placebo or gabapentin preoperatively, and continued postoperatively until discharge. Intraoperative anesthetic and other postoperative pain management strategies will be standardized. Postoperative delirium will be measured using structured interviews. Cognitive function will be measured using a battery of neurocognitive tests pre- and post-operatively. Using an intention to treat strategy, we, the researchers at UCSF, will compare the amount of postoperative pain, narcotic requirements, and postoperative delirium and cognitive dysfunction between the two groups. |
| Detailed Description | Postoperative delirium is a common condition, occurring in 10-70% of surgical patients after major surgery. To date, few studies have examined events in the postoperative period as contributing factors to postoperative delirium. We recently completed a study in over 500 geriatric surgical patients to examine whether the mode of postoperative analgesia delivery, medication types, and the severity of postoperative pain may impact the occurrence of postoperative delirium. In this study, 46% of patients developed postoperative delirium on either the first or second postoperative day. By multivariate logistic regression, variables which had independent association with postoperative delirium included age ≥80 years, moderate to severe preoperative resting pain, and increased level of resting pain postoperatively in comparison with preoperative baseline. When the analysis was focused on patients who used Patient Controlled Analgesia (PCA) alone for postoperative pain control, the amount of narcotic used (hydromorphone) was significantly higher in those with postoperative delirium as compared to those without, suggesting that inadequate pain control and/or the central effects of opioids may be associated with postoperative delirium. Since increasing the doses of opioids in the elderly patients will likely lead to unwanted side effects such as respiratory depression, the addition of a non-opioid agent may result in a narcotic-sparing effect, and also reducing pain postoperatively. Gabapentin is a structural analog of gamma-amino butyric acid, and has been used as an anti-convulsant and anti-nociceptive drug. It is not metabolized in humans (therefore no hepatic enzyme induction), and is eliminated from the body by renal clearance. In animal studies, gabapentin has been demonstrated to be effective in reducing both allodynia and hyperalgesia, and may have selective effect on the nociceptive process involved in central sensitization. Gabapentin has been successfully used in the treatment of neuropathic pain and other painful conditions. Recently, there is substantial evidence to suggest that gabapentin also may be useful in the treatment of postoperative pain. To date, there have been nine randomized clinical trials of gabapentin versus placebo including a total of over 700 patients. Taken together, these studies reported that gabapentin given perioperatively significantly reduced postoperative analgesic requirements, and had minimum side effects. The only reported significant side effects in these trials were mild sedation in two studies. In patients with epilepsy, gabapentin can be introduced at therapeutic doses, and presents no safety or serious side effect issues. Since gabapentin has negligible protein binding, it has no interactions with other medications. It is recommended that metabolic and laboratory monitoring is not necessary, and excellent cognitive profile is evident. At UCSF, gabapentin has been used safely in a relatively large number of patients on an empiric bases in the postoperative period, typically in surgical patients with substantial chronic pain, and more recently, in patients who have undergone spinal surgery as an adjuvant agent to narcotics to relieve postoperative radicular pain (personal communication with Peter Koo, Clinical Pharmacist at UCSF). Typically, patients are started on gabapentin 300 mg po TID on the first day, rapidly escalating to 600 mg TID on the second day, and finally to 900 mg TID the third day until discharge. The UCSF experience suggests that gabapentin is well tolerated with minimal side effects. Hypothesis We hypothesize that intensive pain management postoperatively using an adjuvant agent, gabapentin, will lead to a decrease in the amount of postoperative pain experienced, thereby resulting in a decrease in the incidence of postoperative delirium in elderly patients undergoing surgery of the spine. Aims 1. To compare the incidence of postoperative delirium and cognitive dysfunction between the placebo vs. the gabapentin groups 2. To compare the amount of postoperative pain between the placebo vs. the gabapentin groups 3. To compare the amount of narcotic used postoperatively between the placebo vs. the gabapentin groups Objectives 1. The broad overall goal is to identify the pathophysiology of postoperative delirium and cognitive dysfunction in older patients 2. To determine whether optimization of postoperative pain control will reduce the incidence of postoperative delirium and cognitive dysfunction |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Postoperative Pain |
| Intervention | Drug: Gabapentin This is a Double blind, placebo-controlled experimental study in which gabapentin adjusted for renal clearance (or placebo) is given preoperatively and also the first three postoperative days Other Names: gabapentin versus placebo |
| Study Arm (s) | Experimental: Gabapentin Double blind, placebo controlled |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
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| Estimated Enrollment | 750 |
| Estimated Completion Date | September 2015 |
| Estimated Primary Completion Date | September 2014 |
| Eligibility Criteria | Inclusion Criteria: - Male or female ≥45 years of age undergoing surgery involving the spine, hip or knee replacement. - English speaking. - Anticipated to stay in the hospital for at least 48 hours. Exclusion Criteria: - Patients who take gabapentin preoperatively, or have known sensitivity to the drug, or those unable to be randomized to receive gabapentin. - Subjects who are unable to provide informed consent. - Patients with a history of narcotic tolerance. - Patients with planned two stage spinal procedures (anterior-posterior spinal fusion to be done on two separate days). |
| Gender | Both |
| Ages | 65 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Jacqueline M Leung, MD, MPH 415-476-0711 leungj@anesthesia.ucsf.edu |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00221338 |
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| Other Study ID Numbers | H5636-26795-01 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University of California, San Francisco |
| Study Sponsor | University of California, San Francisco |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Jacqueline M Leung, MD, MPH University of California, San Francisco, CA, USA |
| Verification Date | January 2014 |
Locations[ + expand ][ + ]
| University of California, San Francisco | San Francisco, California, United States, 94143-0648 Contact: Gabriela Meckler, BS | 415-476-9489 | mecklerg@anesthesia.ucsf.eduPrincipal Investigator: Jacqueline M Leung, MD, MPH Recruiting |
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