Stanford Accelerated Recovery Trial (START)

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01067144
• Collaborator: (none)
• Enrollment: 422
• Location: 1
• Arms: 2
• Duration (Months): 74
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pain; Breast Cancer; Lung Cancer	Drug: Gabapentin; Drug: Lorazepam (active control); Drug: Placebo (inactive)	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 422 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Stanford Accelerated Recovery Trial (START)
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

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: Fanatrex Gabarone Gralise Neurontin Nupentin

Outcome Measures

Primary Outcome Measures

1. Time to Pain Resolution [Up to 2 years]

   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.

Secondary Outcome Measures

1. Time to Opioid Cessation [Up to 2 years]

   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.

2. Count of Participants With Continued Pain at 6 Months [Month 6]

   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).

3. Count of Participants With Continued Pain at 1 Year [Year 1]

   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).

4. Count of Participants With Continued Opioid Use at 6 Months [Month 6]

   Continued opioid use was defined as any report of any continued opioid use at Month 6.

5. Count of Participants With Continued Opioid Use at 1 Year [Year 1]

   Continued opioid use was defined as any report of any continued opioid use at Year 1.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Ian R Carroll, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Hah, Assistant Professor of Anesthesiology, Perioperative and Pain Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT01067144
• Other Study ID Numbers: IRB-16617; SU-02032010-4882; VAR0054
• First Posted: Feb 11, 2010
• Last Update Posted: May 5, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Additional relevant MeSH terms: Gabapentin; Lorazepam

Study Results

Participant Flow

Pre-assignment Detail	1805 patients were assessed for eligibility; 422 were enrolled and randomized.

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Period Title: Treatment
STARTED	207	215
COMPLETED	203	208
NOT COMPLETED	4	7
Period Title: Treatment
STARTED	203	208
Intention-to-Treat Analysis Set	202	208
COMPLETED	144	152
NOT COMPLETED	59	56

Baseline Characteristics

Arm/Group Title	Control	Gabapentin	Total
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.	Total of all reporting groups
Overall Participants	202	208	410
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.4 (11.8)	57.0 (11.7)	56.7 (11.7)
Sex: Female, Male (Count of Participants)
Female	123 60.9%	120 57.7%	243 59.3%
Male	78 38.6%	87 41.8%	165 40.2%

Outcome Measures

1. Primary Outcome

Title	Time to Pain Resolution
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Analysis Set

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Measure Participants	202	208
Median (Inter-Quartile Range) [days]	73	84

2. Secondary Outcome

Title	Time to Opioid Cessation
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Analysis Set

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Measure Participants	202	208
Median (Inter-Quartile Range) [days]	32	25

3. Secondary Outcome

Title	Count of Participants With Continued Pain at 6 Months
Description	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).
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Analysis Set

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Measure Participants	202	208
Count of Participants [Participants]	37 18.3%	42 20.2%

4. Secondary Outcome

Title	Count of Participants With Continued Pain at 1 Year
Description	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).
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Analysis Set

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Measure Participants	202	208
Count of Participants [Participants]	18 8.9%	21 10.1%

5. Secondary Outcome

Title	Count of Participants With Continued Opioid Use at 6 Months
Description	Continued opioid use was defined as any report of any continued opioid use at Month 6.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Analysis Set

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Measure Participants	202	208
Count of Participants [Participants]	4 2%	5 2.4%

6. Secondary Outcome

Title	Count of Participants With Continued Opioid Use at 1 Year
Description	Continued opioid use was defined as any report of any continued opioid use at Year 1.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

Intention-to-Treat Analysis Set

Arm/Group Title	Control	Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.	1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
Measure Participants	202	208
Count of Participants [Participants]	3 1.5%	4 1.9%

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Control		Gabapentin
Arm/Group Description	Active placebo (lorazepam 0.5 mg) given pre-operatively, followed by inactive placebo for 10 doses post-operatively.		1200 mg Gabapentin preoperative dose, 300 mg of Gabapentin 3-times a day postoperative doses for 72-hour post-surgical period.
All Cause Mortality
	Control		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/202 (1%)		2/208 (1%)
Blood and lymphatic system disorders
Postoperative hemodynamic instability	1/202 (0.5%)		0/208 (0%)
Hematoma	1/202 (0.5%)		0/208 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/202 (0%)		1/208 (0.5%)
Pneumothorax	0/202 (0%)		1/208 (0.5%)
Other (Not Including Serious) Adverse Events
	Control		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	191/202 (94.6%)		208/208 (100%)
Eye disorders
Visual disturbance	45/202 (22.3%)		63/208 (30.3%)
Eye pain	19/202 (9.4%)		26/208 (12.5%)
Gastrointestinal disorders
Abdominal pain	44/202 (21.8%)		30/208 (14.4%)
Diarrhea	8/202 (4%)		11/208 (5.3%)
Dry mouth	184/202 (91.1%)		192/208 (92.3%)
Constipation	147/202 (72.8%)		128/208 (61.5%)
Nausea	125/202 (61.9%)		117/208 (56.3%)
Vomiting	55/202 (27.2%)		49/208 (23.6%)
Sore throat	113/202 (55.9%)		104/208 (50%)
General disorders
Leg swelling	56/202 (27.7%)		49/208 (23.6%)
Generalized weakness	122/202 (60.4%)		119/208 (57.2%)
Nervous system disorders
Headache	68/202 (33.7%)		81/208 (38.9%)
Impaired coordination	66/202 (32.7%)		89/208 (42.8%)
Memory	72/202 (35.6%)		75/208 (36.1%)
Skin and subcutaneous tissue disorders
Rash	14/202 (6.9%)		27/208 (13%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.