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

• ClinicalTrials.gov Identifier: NCT01265056
• Recruitment Status: Completed
• First Posted: December 22, 2010
• Results First Posted: February 26, 2013
• Last Update Posted: January 23, 2018
• Sponsor: Lucy A Wibbenmeyer
• Information provided by (Responsible Party): Lucy A Wibbenmeyer, University of Iowa

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pain; Burn Injury	Drug: Gabapentin; Drug: Placebo	Not Applicable

Detailed Description:

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Participant, Care Provider and Investigator are all masked.
• Primary Purpose: Treatment
• Official Title: The Effect of Neurontin on Pain Management in the Acutely Burned Patient
• Actual Study Start Date: February 2010
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Sugar Pill; Placebo	Drug: Placebo; Sugar Pill is administered similar to the protocol used for the investigational drug.
Experimental: Gabapentin; Gabapentin	Drug: Gabapentin; 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.; Other Name: Neurontin

Outcome Measures

Primary Outcome Measures :

1. Opioid Consumption Between the Treatment and the Control Groups (Morphine Equivalents) [ Time Frame: From time of enrollment to 2 weeks after being discharged ]

Secondary Outcome Measures :

1. Psychological Functioning as Evaluated by the Brief Symptom Inventory (BSI) Between Treatment and Placebo Groups [ Time Frame: First Clinic Follow Up After Discharge ]
   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.
2. Difference in Psychological Outcomes on the Sickness Inventory Profile (SIP) [ Time Frame: First Clinic Follow Up After Discharge ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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%

Contacts and Locations

Locations

United States, Iowa

University of Iowa Burn Center

Iowa City, Iowa, United States, 52241

Sponsors and Collaborators

Lucy A Wibbenmeyer

Investigators

• Principal Investigator: Lucy Wibbenmeyer, MD; University of Iowa

More Information

Publications:

Gibran NS; Committee on Organization and Delivery of Burn Care, American Burn Association. Practice Guidelines for burn care, 2006. J Burn Care Res. 2006 Jul-Aug;27(4):437-8.

Cuignet O, Pirson J, Soudon O, Zizi M. Effects of gabapentin on morphine consumption and pain in severely burned patients. Burns. 2007 Feb;33(1):81-6. Epub 2006 Oct 30.

Summer GJ, Puntillo KA, Miaskowski C, Green PG, Levine JD. Burn injury pain: the continuing challenge. J Pain. 2007 Jul;8(7):533-48. Epub 2007 Apr 16. Review.

Dierking G, Duedahl TH, Rasmussen ML, Fomsgaard JS, Møiniche S, Rømsing J, Dahl JB. Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial. Acta Anaesthesiol Scand. 2004 Mar;48(3):322-7.

Gray P, Williams B, Cramond T. Successful use of gabapentin in acute pain management following burn injury: a case series. Pain Med. 2008 Apr;9(3):371-6. doi: 10.1111/j.1526-4637.2006.00149.x.

Dworkin RH. An overview of neuropathic pain: syndromes, symptoms, signs, and several mechanisms. Clin J Pain. 2002 Nov-Dec;18(6):343-9. Review.

Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice ASC, Stacey BR, Treede RD, Turk DC, Wallace MS. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007 Dec 5;132(3):237-251. doi: 10.1016/j.pain.2007.08.033. Epub 2007 Oct 24. Review.

• Responsible Party: Lucy A Wibbenmeyer, Associate Clinical Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT01265056
• Other Study ID Numbers: 200909736
• First Posted: December 22, 2010
• Results First Posted: February 26, 2013
• Last Update Posted: January 23, 2018
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Researchers can contact me (lucy-wibbenmeyer@uiowa.edu) for study protocol or statistical plan.
• Supporting Materials: Study Protocol
• Time Frame: Data is available
• Access Criteria: Email permission. Deidentified information only

Additional relevant MeSH terms:

Burns; Wounds and Injuries; Gabapentin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimanic Agents