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Gabapentin as a Pre-emptive Analgesic in Oral and Maxillofacial Surgical Procedures

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ClinicalTrials.gov Identifier: NCT02957097
Recruitment Status : Not yet recruiting
First Posted : November 6, 2016
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
Jeffry R. Shaefer, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE July 21, 2016
First Posted Date  ICMJE November 6, 2016
Last Update Posted Date August 15, 2019
Estimated Study Start Date  ICMJE September 2019
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2016)
  • Intensity of pain [ Time Frame: 6 hours postoperatively ]
    Pain score of participants on a likert type pain scale (0-10), where 0 is indicative of no pain, and 10 indicates worst pain imaginable.
  • total opioid consumption [ Time Frame: 24 hours ]
    Consumption of opioid medication postoperatively
  • time to first rescue analgesic [ Time Frame: post-operatively (up to 6 hours) ]
  • incidence of adverse effects [ Time Frame: post-operatively (up to 24 hours) ]
  • Intensity of pain [ Time Frame: 12 hours postoperatively ]
    Pain score of participants on a likert type pain scale (0-10), where 0 is indicative of no pain, and 10 indicates worst pain imaginable.
  • Intensity of pain [ Time Frame: 24 hours postoperatively ]
    Pain score of participants on a likert type pain scale (0-10), where 0 is indicative of no pain, and 10 indicates worst pain imaginable.
  • Intensity of pain [ Time Frame: 72 hours postoperatively. ]
    Pain score of participants on a likert type pain scale (0-10), where 0 is indicative of no pain, and 10 indicates worst pain imaginable.
  • total opioid consumption [ Time Frame: 72 hours post-operatively ]
    Consumption of opioid medication postoperatively.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2016)
  • incidence of pain [ Time Frame: 1 month ]
    incidence of pain after 1 month postoperatively
  • intensity of pain on a numeric rating scale (0-10) [ Time Frame: 1 month ]
    intensity of pain after 1 month post-operative. Pain score of participants on a likert type pain scale (0-10), where 0 is indicative of no pain, and 10 indicates worst pain imaginable.
  • length of post-operative hospital-stay [ Time Frame: postoperatively in terms of days (up to 1 week) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gabapentin as a Pre-emptive Analgesic in Oral and Maxillofacial Surgical Procedures
Official Title  ICMJE Gabapentin as a Pre-emptive Analgesic in Oral and Maxillofacial Surgical Procedures
Brief Summary The purpose of this study is to assess the effectiveness of pre-operative administration of gabapentin 900 mg in management of acute post-operative pain in patients undergoing oral and maxillofacial surgical procedures.
Detailed Description

Pain after surgery is a significant acute clinical symptom. It is associated with quality of post-operative recovery, time spent in the hospital, post-discharge care and readmissions, morbidity, psychosocial distress, and cost of care. The management of acute postsurgical pain primarily consists of a multimodal approach consisting of opioids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and local anesthetics. The associated adverse effects often limit the use of such multimodal pharmacotherapy. Opioids have excellent analgesic properties, however are associated with poor adverse-effects profile. They have been associated with nausea, vomiting, somnolence, and urinary retention. Such adverse-effects may decrease the quality of post-operative recovery, increase patient post-surgical management, and overall cost of care. Moreover, in patients undergoing oral and maxillofacial surgical procedures, such adverse-effects may be further potentiated due to placement of reconstructive plates, screws, and maxillomandibular fixation. In order to improve post-surgical quality of care, researchers have been looking for alternative modalities for the management of acute post-surgical pain. One of such modalities has been use of preemptive analgesic therapy. Preemptive analgesia is defined as a treatment modality that is initiated before a traumatic event, such as, surgical incision or tissue manipulation is introduced. Gabapentin is an antiepileptic drug that has been used in the management of painful neuropathies, such as, diabetic poly-neuropathy, post-herpetic neuralgia, and trigeminal neuropathy. Gabapentin has antiallodynic and antihyperalgesic properties with only a minor effect on normal nociception. It reduces the hyperexcitability of dorsal horn neuron induced by tissue injury, as well as, central sensitization induced after trauma and surgery. Gabapentin has been studied extensively as a preemptive analgesic in various non-craniofacial surgeries. In a systemic review and meta-analysis on the pre-operative administration of gabapentin during various surgical procedures, Tiippana et al reported the opioid-sparing effect during the first 24 h after a single dose of gabapentin 300-1200 mg, administered 1-2 h preoperatively, ranged from 20% to 62%. Authors further concluded that the combined effect of a single dose of gabapentin was a reduction of opioid consumption equivalent to 30 +/- 4 mg of morphine (mean +/- 95% confidence interval) during the first 24 h after surgery. In another meta-regression analysis authors reported that gabapentin reduced opioid related adverse effects, such as nausea, vomiting, and urinary retention (Numbers needed to treat (NNT) 25, 6, and 7, respectively). In a systematic review and meta-analysis, consisting of randomized controlled trials of women who underwent a total abdominal hysterectomy, under general anesthesia, it was concluded that preemptive administration of gabapentin was effective in decreasing postsurgical pain scores, narcotic consumption, and nausea and vomiting episodes. Similar reduction in postsurgical pain scores, narcotic consumption, and adverse effects were seen after other surgical procedures, such as, breast surgery, spinal surgery, orthopedic surgical procedures, and amputation surgery. However, no such data is available for major oral and maxillofacial surgical procedures

Primary and secondary aims are as following:

Primary aims:

  1. To determine the difference in the intensity of pain, post-operatively, at 6 hours, 12 hours, 24 hours, and 72 hours between participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.
  2. To determine the difference in the total opioid consumption at 24 and 72 hours post-operatively, among participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.
  3. To evaluate the difference in the time to first rescue analgesic post-operatively, among participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.
  4. To determine the difference in the incidence of adverse effects within first 24 hours and 72 hours post-operatively between participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.

Secondary aims:

  1. To determine the difference in the incidence and the intensity of pain at 1 month post-operatively, among participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.
  2. To evaluate the differences in post-operative hospital-stay among participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.
  3. To evaluate the influence of a history of a chronic pain disorder on:

    1. The association between intensity of pain and pre-emptive use of gabapentin.
    2. The association between opioid consumption and pre-emptive use of gabapentin.
    3. The difference in the time to first rescue analgesic post-operatively, among participants pre-operatively administered gabapentin versus those pre-operatively administered a placebo medication.

Hypothesis:

  1. Participants receiving gabapentin 900 mg PO 3h pre-operatively will have significantly less pain at 6 hours, 12 hours, 24 hours, and 72 hours post-operatively compared to those receiving placebo medication.
  2. Participants receiving gabapentin 900 mg 3h pre-operatively will have significantly less total opioid consumption at 24 and 72 hours post-operatively than those receiving placebo medication.
  3. There will be significantly fewer incidences of adverse events associated with opioid consumption in participants with pre-emptive use of gabapentin medication.
  4. The gabapentin group will have significantly longer time to first rescue medication compared to the placebo group.

Study enrollment will be carried out in the department of Oral and Maxillofacial Surgery (OMFS), Massachusetts General Hospital, Boston, Massachusetts. Relevant patients are going to be identified and offered to participate in the study. This will take place during the history and physical examination visit, which is conducted prior to any surgical procedure in the department of OMFS.

This will be a double-blind investigation, randomized, placebo-controlled drug trial. Randomization of treatment group will be carried out by the hospital pharmacy using a computer generated randomization template. Both investigator and participant will be blind to the group allotment.

The investigation is primarily divided into two sections, the medication phase and the surgical phase. In the medication phase of the investigation, treatment group will receive a single dose of Gabapentin 900mg 2-3h before commencement of surgery (initial incision). Placebo group will receive a single dose of placebo medication 2-3h pre-operatively (before commencement of surgery). Both gabapentin and placebo medication will look similar in shape, color, and size. Hospital pharmacy will be recruited to provide the placebo and gabapentin medications. Hospital pharmacy will be responsible for delivering the medication to the participant prior to the surgical procedure.

During the surgical phase of the study, all of the participants will undergo respective oral and maxillofacial surgical procedure, under general anesthesia. The surgical part of this investigation will not, in any way or form, be different than the usual standard of care followed by the department of oral and maxillofacial surgery department, at Massachusetts General Hospital. Peri-operative and post-operative analgesic regimens will also be standardized as per departmental guidelines for the respective surgical procedures.

Data that will be collected consists of following:

Prior to undergoing surgical procedure

  1. Age, gender, past medical history, medical illnesses, past surgical history, past hospitalization history, psychosocial history, current medications, allergies.
  2. Graded chronic pain scale - 6 months
  3. McGill Pain-short questionnaire

After the surgical procedure

  1. Surgical characteristics such as, type of surgery, surgeon who performed the surgery, complications during surgery, duration of surgery
  2. Pain score on an 11-point likert-type visual analog scale at 6h, 12h, 24h, 72h, 1 month post-surgically.
  3. Opioid consumption at 24h and 72h post-operatively
  4. Vomiting/Nausea score on an 11-point likert-type visual analog scale at 6h, 12h, 24h, and 72h post-surgically.
  5. Opioid-related symptom distress scale at 24h and 72h, post-surgically
  6. Duration of hospital stay
  7. Analgesic medication regimen after 1 month post-operatively.

All of the data will be collected over 7 data collection points.

Screening phase:

Screening visit. Interested participant will undergo screening and evaluation. Participants will be explained the study and consent will be obtained.

Participants willing to participate will also fill out following questionnaires:

  • Graded Chronic Pain Scale 6 months
  • McGill pain questionnaire

Surgical phase:

Baseline visit. Participants will be administered either a single tablet of gabapentin 900 mg or a placebo medication, 2-3 hours before undergoing surgical procedure.

Follow-up phase:

Follow-up 1. It will be carried out 6 hours post-surgically. Participant will be asked to rate the level of pain, and intensity of nausea and vomiting on an 11-point likert type 0 to 10 scale, where 0 is indicative of no symptom and 10 is indicative of worst symptom ever. In addition, information from the medical record regarding the characteristics of the surgical procedure (type, surgeon, duration, complications) will be collected.

Follow-up 2, 3, and 4. Follow-up 2, 3, and 4 will be carried out post-operatively, after 12 hours, 24 hours, and 72 hours, respectively. Participant will be asked same questions as in step 3. In addition participants use of analgesic medication and stay in hospital will be recorded. Further more, during follow-up 3 and 4 (24 and 72 hours post-operative, respectively) participants will fill out opioid-related symptom distress scale and data on type, dosage, and quantity of opioid medications consumed will be collected. If participant leaves hospital prior to any of the follow-up visits, they will be contact via telephone.

Follow-up 5. These will be carried out over the phone, at 1 month post-surgically. Following data will be collected:

  1. Participants will be asked questions from McGill pain-short questionnaire and opioid-related symptom distress scale.
  2. Intensity of nausea and/or vomiting on a 0 to 10 scale, where 0 is indicative of no nausea and/or vomiting and 10 is indicative of worst nausea/vomiting ever.
  3. List of analgesic medications.

All types of opioid medications used during the investigation period for management of pain will be converted to morphine sulphate PO equivalent at 0 % cross-reactivity resistance.

BIOSTATISTICAL ANALYSIS

A total of 100 participants are going to be recruited for the present investigation. This number was calculated using either effect size of 25% less consumption of opioid medications, or 25% less pain score at 6h post-operatively, and alpha value of 0.05 and power of 0.95. However, if 100 participants are not recruited by 12 months, recruitment process will be terminated.

A multistep analytic approach will be carried out. In the first step, participants' demographics, and clinical characteristics are going to be compared among participants of the treatment and the placebo group, using t-tests (or non-parametric equivalent) and Chi-squared (or Fisher exact) tests where appropriate. Next, using univariate and multivariate logistic regression analyses are going to be used to determine the efficacy of the drug.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pain, Postoperative
  • Acute Pain
  • Facial Pain
Intervention  ICMJE
  • Drug: Gabapentin
    Medication used for management of neuropathic pain conditions
    Other Names:
    • Neurontin
    • Gralise
    • Horizant
  • Drug: Placebo
    Placebo medication. It looks exactly same as the Gabapentin medication in same size, shape, and color.
Study Arms  ICMJE
  • Experimental: Medication - Gabapentin
    Participants of this group will be administered either Gabapentin 900 milligram PO 2-3 hours prior to the surgical procedure.
    Intervention: Drug: Gabapentin
  • Placebo Comparator: Medication - Placebo
    Participants of this group will be administered either Placebo PO 2-3 hours prior to the surgical procedure.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 23, 2017)
30
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2016)
100
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants, of any race, between ages of 18 - 65 years.
  2. Participants undergoing unilateral or bilateral Lefort osteotomy, unilateral or bilateral mandibular inverted-L or sagittal split osteotomy with or without genioplasty, temporomandibular joint arthroplasty with or without total joint replacement prosthesis.

Exclusion Criteria:

  1. Participants who are pregnant.
  2. Participants allergic to gabapentin.
  3. Participants with a history of alcohol, or drug abuse.
  4. Participants who are unwilling to participate, or are non-compliant to the guidelines of the investigation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Steven J Scrivani, DDS, DMedSc 617-726-8222 Sscrivani1@partners.org
Contact: Khawaja S Nasir, BDS, MS 435-710-1080 ksnasir@partners.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02957097
Other Study ID Numbers  ICMJE ksn17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jeffry R. Shaefer, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Massachusetts General Hospital
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP