Stanford Accelerated Recovery Trial (START)

The goal of this study is to determine whether administering Gabapentin prior to surgery affects duration of pain and opioid use post-surgery. The investigators aim to compare gabapentin to placebo in a prospective, randomized clinical trial in which patients will be followed post-surgery until pain resolves and opioid use ceases.

Study Overview

• Status: Terminated
• Conditions: Pain; Breast Cancer; Lung Cancer
• Intervention / Treatment: Drug: Lorazepam (active control); Drug: Placebo (inactive); Drug: Gabapentin

Detailed Description

Gabapentin was originally developed as an anti-convulsant, but was quickly recognized as a medication with significant analgesic activity in patients with neuropathic pain. More recently it has begun to be appreciated that it may have some benefits in the peri-operative period. Pre-operative Gabapentin reduces preoperative anxiety, early post-operative pain severity, post-operative opioid use and post-operative delirium (presumably through reduced opioid consumption). These same attributes are shared by medications such as NSAIDS and tylenol and the use of peri-operative gabapentin has not permeated the standard of care. Early post-operative pain severity and preoperative anxiety have been implicated in our own research as risk factors for prolonged time to pain resolution and prolonged time to opioid cessation. Since these endpoints are generally synonymous with time to recovery, interventions reducing these times would be seen not just to increase comfort but to actually speed recovery.

• Study Type: Interventional
• Enrollment (Actual): 422
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

• Age 18 to 75
• Undergoing a scheduled surgery
• English speaking
• Ability and willingness to complete questionnaires or use Palm Pilot

EXCLUSION CRITERIA

• Known kidney disease
• Currently receiving gabapentin or (pregabalin) lyrica already
• Cognitive impairment
• Previous history of excessive sedation or adverse reaction to gabapentin (not it was tried but ineffective for nerve pain)
• Coexisting chronic pain > 4/10 disorder in area other than surgical target
• Plan to move out of state
• Condition that would in judgment of team member make patient likely to be lost to follow-up
• Elevated suicidality
• Known pregnancy
• Current symptoms of ataxia, dizziness, or sedation
• Narrow angle glaucoma
• Severe respiratory insufficiency (ie, severe emphysema or chronic obstructive pulmonary disease)
• History of gastric bypass surgery and obstructive sleep apnea requiring continuous positive airway pressure (CPAP)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Active placebo given pre-operatively, followed by inactive placebo for 10 doses post-operatively	Drug: Lorazepam (active control); 0.5 mg Lorazepam (active control) given pre-operatively in a single dose.; Drug: Placebo (inactive); 2 capsules of inactive placebo given 3-times a day post-operatively for the 72-hour post-surgical period.
Experimental: Gabapentin; 1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.	Drug: Gabapentin; 1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.; Other Names: Gralise; Neurontin; Gabarone; Fanatrex; Nupentin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Pain Resolution	Time to pain resolution was defined as 5 consecutive reports of "0" average pain at the surgical site (as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain). Planned call frequency was daily for 3 months, weekly thereafter up to 6 months, and monthly thereafter up to 2 years after surgery.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Opioid Cessation	Time to opioid cessation was defined as 5 consecutive reports of no opioid use. Planned call frequency was daily for 3 months, weekly thereafter up to 6 months, and monthly thereafter up to 2 years after surgery.	Up to 2 years
Count of Participants With Continued Pain at 6 Months	Continued pain was defined as a report of at least "1" average pain at the surgical site (as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain).	Month 6
Count of Participants With Continued Pain at 1 Year	Continued pain was defined as a report of at least "1" average pain at the surgical site (as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain).	Year 1
Count of Participants With Continued Opioid Use at 6 Months	Continued opioid use was defined as any report of any continued opioid use at Month 6.	Month 6
Count of Participants With Continued Opioid Use at 1 Year	Continued opioid use was defined as any report of any continued opioid use at Year 1.	Year 1

Collaborators and Investigators

• Sponsor: Stanford University

Publications and helpful links

General Publications

• Hah J, Mackey SC, Schmidt P, McCue R, Humphreys K, Trafton J, Efron B, Clay D, Sharifzadeh Y, Ruchelli G, Goodman S, Huddleston J, Maloney WJ, Dirbas FM, Shrager J, Costouros JG, Curtin C, Carroll I. Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial. JAMA Surg. 2018 Apr 1;153(4):303-311. doi: 10.1001/jamasurg.2017.4915. Erratum In: JAMA Surg. 2018 Apr 1;153(4):396. JAMA Surg. 2022 Jun 1;157(6):553.
• Hah JM, Cramer E, Hilmoe H, Schmidt P, McCue R, Trafton J, Clay D, Sharifzadeh Y, Ruchelli G, Goodman S, Huddleston J, Maloney WJ, Dirbas FM, Shrager J, Costouros JG, Curtin C, Mackey SC, Carroll I. Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2019 Mar 1;2(3):e190168. doi: 10.1001/jamanetworkopen.2019.0168. Erratum In: JAMA Netw Open. 2022 Apr 1;5(4):e229747.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 9, 2010
• First Submitted That Met QC Criteria: February 10, 2010
• First Posted (Estimate): February 11, 2010

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Antimanic Agents; Gabapentin; Lorazepam
• Other Study ID Numbers: IRB-16617; SU-02032010-4882 (Other Identifier: Stanford University); VAR0054 (Other Identifier: OnCore)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes