The Effect of Neurontin on Pain Management in the Acutely Burned Patient

Study Overview
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Brief Summary
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Burn patients have extreme pain. Opioids are the main agents used for analgesia. We therefore propose a single center study to fruther assess the efficacy of neuropathic agents in controlling the pain associated with acute thermal injury.

Detailed Description
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The study was conducted in a 16-bed American Burn Association certified burn unit. Patients age >18 years old, with at least a 5% burn injury and an expected length of stay (LOS) of 48 hours, were approached for enrollment in this prospective, placebo controlled randomized study. Patients who were pregnant, lactating, prisoners or who had renal insufficiency were excluded. After consent, patients were assigned to either placebo or Gp by random numbers generated in Microsoft Excel (2010). Both the drug and the placebo were over-encapsulated to appear identical. The placebo pills contained starch. The research clinical pharmacist was the only unblinded staff member and did not participate in clinical care of the patients. Following randomization, patients received a loading dose of study drug on day one and began three times a day (TID) dosing per the dose escalation schedule the following day. At discharge, patients were given a three day taper per the dose de-escalation schedule Patients were assessed for completion of psychosocial adjustment (Brief Symptom Inventory, BSI, and Sickness Inventory Profile, SIP) at their first clinic visit. Agents used for pain control included: acetaminophen, non-steroidal anti-inflammatories, morphine instantaneous release and morphine extended release. In the case of allergies or ineffectiveness, other agents were occasionally used. Short acting morphine was ordered every two hours prn and hydromorphone was ordered every four hours as needed. All were converted to morphine equivalents. The study was powered to detect a 22% difference in opioid consumption between the two groups based on the work by Cuignet et al. It was estimated that a total of 50 patients were needed to achieve an alpha of 0.05 and a beta of 0.80 to detect the difference in the primary endpoint. For statistical purposes, conversion tables were used to convert all opioid medications into morphine equivalents with 1 morphine equivalents (ME)=30mg oral morphine. The primary outcome variable (morphine consumption) were adjusted for days past injury. The BSI and SIP scales were scored according to study directions. Both an intention to treat and actual treatment analysis were performed using Stata 11.2 for Windows (Stata Corp. College Station, Texas, U.S.A.). Continuous variables between groups were analyzed with the students T test. Categorical variables were analyzed with the Chi Square test or Fischer Exact Test where appropriate. A random effects model adjusting for confounders was used to assess the effect of treatment on the outcome measures. The study was approved by the University's Institutional Review Board and was registered with the clinical trials association (200909736).

Official Title
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The Effect of Neurontin on Pain Management in the Acutely Burned Patient

Conditions
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Pain, Burn Injury

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All admitted patients with LOS expected to be > 48 hours (usually burn injury > 5%) > 18 years of age Thermal injury to skin Exclusion Criteria: Prisoners Pregnant or nursing women Children <18 years of age Frostbite or non thermal injury to skin Renal insuffiency (creatinine clearance < 60mL/min) or failure (on renal replacement) Expected length of stay < 48 hours (this usually includes burn <5%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar Pill<br>Placebo | Drug: Placebo<br>* Sugar Pill is administered similar to the protocol used for the investigational drug.<br>|
| Experimental: Gabapentin<br>Gabapentin | Drug: Gabapentin<br>* On Study day 1: 1200mg (single dose). Study day 2,3: 300mg TID, 900mg daily. Study day 4-7: 600mg TID 1800mg* daily. Study day 8-11: 800mg TID 2400mg* daily [Optional increase to 2400 if pain scores are still 4 on NRS] Study day 11: 1200mg TID 3600mg* daily [Optional increase to 3600 if pain scores are still >4 on NRS] * May revert back to prior dose if adverse symptoms occur and are thought to be drug related. Up titration then will be preformed in 48 hours following deexcalation.<br>* Other names: Neurontin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Consumption Between the Treatment and the Control Groups (Morphine Equivalents) |  | From time of enrollment to 2 weeks after being discharged | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychological Functioning as Evaluated by the Brief Symptom Inventory (BSI) Between Treatment and Placebo Groups | The Brief Symptom Inventory 18 (BSI 18) is designed with reliability in mind. The BSI 18 assessment gathers patient-reported data to help measure psychological distress and psychiatric disorders in medical and community populations. As the latest in an integrated series of test instruments that include the SCL-90-R®, BSI® (53 questions), and DPRS® instruments, the BSI 18 test offers a more effective, easy-to-administer tool to help support clinical decision-making and monitor progress throughout treatment. BSI-18 measures three dimensions with 6 questions a piece (somatization , depression , anxiety) and overall psychological distress scores (Global severity index, GSI). Each of the 18 items range from a score of 0-4; total score ranges from 0-72 with higher scores indicating worse function. The GSI score is calculated as the mean of the three subscales. The study reported the GSI score. Higher score is worse. | First Clinic Follow Up After Discharge | 
| Difference in Psychological Outcomes on the Sickness Inventory Profile (SIP) | The sickness inventory profile (SIP) is a behaviorally based measure of health status. Scores range from 0-68 with higher numbers indicating worse outcomes. The study report total SIP score. The higher the score the worse the function. | First Clinic Follow Up After Discharge |