Bunionectomy Study (0000-063)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00601458
• Collaborator: (none)
• Enrollment: 100
• Arms: 3
• Duration (Months): 6

Study Details

Study Description

Brief Summary

We are interested in whether bunionectomy can be used as a model to study the treatment of acute pain. It has been used to study the effect of Non-Steroidal Anti-inflammatory (NSAIDS) medications (such as ibuprofen) and other pain relieving drugs. We are interested to know if this model is useful to study other drugs for the treatment of acute pain. The other drugs being tested in this study are pregabalin and naproxen sodium. These drugs are approved for use by the Food and Drug Administration (FDA). This study is designed to test whether these two drugs are effective in treating pain after a bunionectomy.

Condition or Disease	Intervention/Treatment	Phase
Acute Pain	Drug: pregabalin; Drug: naproxen sodium; Drug: Comparator: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Pregabalin and Naproxen Sodium on Postoperative Pain After Bunionectomy
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: Pregabalin 300 mg	Drug: pregabalin; Patients will be randomized just prior to surgery to 1 of 3 study treatments: pregabalin (300 mg) treatment will be administered approximately 1 hour prior to surgery. Postoperatively, pregabalin (150 mg) will be dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.
Active Comparator: Arm 2: naproxen sodium 550 mg	Drug: naproxen sodium; Patients will be randomized just prior to surgery to 1 of 3 study treatments: naproxen sodium (550 mg) treatment will be administered approximately 1 hour prior to surgery. Postoperatively, naproxen sodium will be dosed starting 12 hours following T=0 and every 12 hours until 36 hours following T=0.; Other Names: naproxen
Placebo Comparator: Arm 3: Placebo	Drug: Comparator: Placebo; Patients will be randomized just prior to surgery to 1 of 3 study treatments: placebo treatment will be administered approximately 1 hour prior to surgery. Postoperatively, placebo will be dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.

Outcome Measures

Primary Outcome Measures

1. Total Patient Controlled Analgesic (PCA) Hydromorphone Consumption Over the 24 Hours Post-surgery [First 24 hours following surgery]

   Total dose (amount) of hydromorphone via patient controlled analgesic (PCA) pump required in the 24 hours post-surgery in each of the treatment arms: placebo, pregabalin 300 mg or naproxen 550 mg.

Secondary Outcome Measures

1. Time to First Request of PCA Hydromorphone [First 24 hours following surgery]

   Time (in hours) to first patient controlled analgesic (PCA) pump use after surgery in each of the treatment arms: placebo, pregabalin 300 mg or naproxen 550 mg.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is a man or woman between 18 and 65 years of age

• For Women of Child-bearing potential: woman who is currently not pregnant not nursing and who is willing to use a medically acceptable method of birth control from the time after the screening visit until completion of the follow-up visit

• Patient is scheduled to have a bunionectomy

• Patient must be willing to stay at the study site throughout the 48-hour observation period following surgery and is willing to complete a 2-week follow up

• Patient is capable of operating a Patient Controlled Analgesia device

Exclusion Criteria:

• Patient is being treated for a disease and has not been on a stable dose of medication for at least 2 weeks prior to surgery

• Patient has used or intends to use any of the medications that are prohibited by the protocol, which could interfere with the evaluation of the study drugs

• Patient has an estimated creatinine clearance of < or = 60 mL per min

• Patient has a history of drug abuse or dependence, or patient has a positive urine drug screen

• Patient has a condition that prevents clear communication concerning pain perception (such as diabetic neuropathy, peripheral neuropathy, etc.)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00601458
• Other Study ID Numbers: 0000-063; 063; 2007_661
• First Posted: Jan 28, 2008
• Last Update Posted: Apr 10, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Merck Sharp & Dohme LLC: Primary, unilateral, first metatarsal bunionectomy with osteotomy
• Additional relevant MeSH terms: Acute Pain; Naproxen; Pregabalin

Study Results

Participant Flow

Recruitment Details	First Patient Entered: 25 July 2007 Last Patient Last Visit: 28 January 2008 1 site

Arm/Group Title	Pregabalin 300 mg	Naproxen Sodium 550 mg	Placebo
Arm/Group Description	Active Comparator: Arm 1: Pregabalin 300 mg Pregabalin (300 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, pregabalin (150 mg) was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.	Active Comparator: Arm 2: Naproxen sodium 550 mg Naproxen sodium (550 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, naproxen sodium was dosed starting at 12 hours following T=0 and every 12 hours until 36 hours following T=0.	Placebo treatment was administered approximately 1 hour prior to surgery. Postoperatively, placebo was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.
Period Title: Overall Study
STARTED	36	34	30
COMPLETED	32	29	28
NOT COMPLETED	4	5	2

Baseline Characteristics

Arm/Group Title	Pregabalin 300 mg	Naproxen Sodium 550 mg	Placebo	Total
Arm/Group Description	Active Comparator: Arm 1: Pregabalin 300 mg Pregabalin (300 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, pregabalin (150 mg) was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.	Active Comparator: Arm 2: Naproxen sodium 550 mg Naproxen sodium (550 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, naproxen sodium was dosed starting at 12 hours following T=0 and every 12 hours until 36 hours following T=0.	Placebo treatment was administered approximately 1 hour prior to surgery. Postoperatively, placebo was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.	Total of all reporting groups
Overall Participants	32	29	28	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.3 (14.1)	40.6 (13.5)	38.8 (11.6)	39.9 (13.1)
Sex: Female, Male (Count of Participants)
Female	27 84.4%	23 79.3%	23 82.1%	73 82%
Male	5 15.6%	6 20.7%	5 17.9%	16 18%
Body Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	72.3 (18.1)	76.7 (17.2)	77.2 (16.9)	75.3 (17.4)
Lidocaine Use (Milliliters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Milliliters]	15.0 (2.3)	15.9 (2.7)	14.6 (1.6)	15.2 (2.2)
Propofol Use (Milligrams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Milligrams]	348.4 (132.9)	364.5 (122.8)	353.9 (105.8)	355.4 (121.1)

Outcome Measures

1. Primary Outcome

Title	Total Patient Controlled Analgesic (PCA) Hydromorphone Consumption Over the 24 Hours Post-surgery
Description	Total dose (amount) of hydromorphone via patient controlled analgesic (PCA) pump required in the 24 hours post-surgery in each of the treatment arms: placebo, pregabalin 300 mg or naproxen 550 mg.
Time Frame	First 24 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregabalin 300 mg	Naproxen Sodium 550 mg	Placebo
Arm/Group Description	Active Comparator: Arm 1: Pregabalin 300 mg Pregabalin (300 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, pregabalin (150 mg) was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.	Active Comparator: Arm 2: Naproxen sodium 550 mg Naproxen sodium (550 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, naproxen sodium was dosed starting at 12 hours following T=0 and every 12 hours until 36 hours following T=0.	Placebo treatment was administered approximately 1 hour prior to surgery. Postoperatively, placebo was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.
Measure Participants	32	29	28
Geometric Mean (Inter-Quartile Range) [milligrams]	2.94	2.07	5.96

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	1-sided alpha = 0.045 Hochberg closed testing procedure
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-50.7
	Confidence Interval	() 97.8%; -73.6 to -8.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The natural log scale treatment difference (pregabalin - placebo) and 97.8% CI for the treatment difference were exponentiated and reported as a percentage reduction in 24-h cumulative hydromorphone consumption.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naproxen Sodium 550 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	1-sided alpha = 0.045 Hochberg closed testing procedure
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-65.4
	Confidence Interval	() 97.8%; -81.7 to -34.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	The natural log scale treatment difference (naproxen - placebo) and 97.8% CI for the treatment difference were exponentiated and reported as a percentage reduction in 24-h cumulative hydromorphone consumption.

2. Secondary Outcome

Title	Time to First Request of PCA Hydromorphone
Description	Time (in hours) to first patient controlled analgesic (PCA) pump use after surgery in each of the treatment arms: placebo, pregabalin 300 mg or naproxen 550 mg.
Time Frame	First 24 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregabalin 300 mg	Naproxen Sodium 550 mg	Placebo
Arm/Group Description	Active Comparator: Arm 1: Pregabalin 300 mg Pregabalin (300 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, pregabalin (150 mg) was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.	Active Comparator: Arm 2: Naproxen sodium 550 mg Naproxen sodium (550 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, naproxen sodium was dosed starting at 12 hours following T=0 and every 12 hours until 36 hours following T=0.	Placebo treatment was administered approximately 1 hour prior to surgery. Postoperatively, placebo was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.
Measure Participants	32	29	28
Median (Inter-Quartile Range) [Hours]	7.3	9.1	5.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 300 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	1-sided alpha = 0.045 Hochberg closed testing procedure
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.46
	Confidence Interval	() 95%; 0.183 to 2.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehmann procedure was used to obtain an estimate of the difference in medians and an exact CI for the difference in medians

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Naproxen Sodium 550 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	1-sided alpha = 0.045 Hochberg closed testing procedure
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	3.70
	Confidence Interval	() 95%; 1.77 to 6.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehmann procedure was used to obtain an estimate of the difference in medians and an exact CI for the difference in medians

Adverse Events

Time Frame	AEs were collected from the time the subject signed consent until 14 days following the last dose of study mediciation.
Adverse Event Reporting Description	AE were assessed by clinical evaluation including vital signs, physical examination. medical history, clinical laboratory safety assessment (chemistry, hematology, urinalysis) and ECG at time points specified in the study. Subjects were queried at each visit for any clinical adverse experiences that may have occurred since the previous visit.
Arm/Group Title	Pregabalin 300 mg		Naproxen Sodium 550 mg		Placebo
Arm/Group Description	Active Comparator: Arm 1: Pregabalin 300 mg Pregabalin (300 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, pregabalin (150 mg) was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.		Active Comparator: Arm 2: Naproxen sodium 550 mg Naproxen sodium (550 mg) treatment was administered approximately 1 hour prior to surgery. Postoperatively, naproxen sodium was dosed starting at 12 hours following T=0 and every 12 hours until 36 hours following T=0.		Placebo treatment was administered approximately 1 hour prior to surgery. Postoperatively, placebo was dosed starting at 8 hours following T=0 and every 8 hours until 40 hours following T=0.
All Cause Mortality
	Pregabalin 300 mg		Naproxen Sodium 550 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin 300 mg		Naproxen Sodium 550 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/34 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Pregabalin 300 mg		Naproxen Sodium 550 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/36 (72.2%)		19/34 (55.9%)		25/30 (83.3%)
Eye disorders
Vision Blurred	0/36 (0%)		0/34 (0%)		1/30 (3.3%)
Gastrointestinal disorders
Abdominal Pain	0/36 (0%)		1/34 (2.9%)		0/30 (0%)
Constipation	2/36 (5.6%)		2/34 (5.9%)		1/30 (3.3%)
Diarrhoea	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Dry Mouth	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Nausea	16/36 (44.4%)		14/34 (41.2%)		21/30 (70%)
Vomiting	7/36 (19.4%)		9/34 (26.5%)		18/30 (60%)
General disorders
Chills	0/36 (0%)		1/34 (2.9%)		0/30 (0%)
Pain	0/36 (0%)		2/34 (5.9%)		0/30 (0%)
Pyrexia	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Investigations
Blood Pressure Decreased	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Oxygen Saturation Decreased	2/36 (5.6%)		0/34 (0%)		3/30 (10%)
Metabolism and nutrition disorders
Anorexia	1/36 (2.8%)		1/34 (2.9%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/36 (5.6%)		0/34 (0%)		0/30 (0%)
Muscle Spasms	0/36 (0%)		1/34 (2.9%)		1/30 (3.3%)
Pain In Extremity	1/36 (2.8%)		0/34 (0%)		1/30 (3.3%)
Nervous system disorders
Dizziness	6/36 (16.7%)		5/34 (14.7%)		3/30 (10%)
Headache	8/36 (22.2%)		1/34 (2.9%)		4/30 (13.3%)
Somnolence	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Tremor	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Psychiatric disorders
Insomnia	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Renal and urinary disorders
Dysuria	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Reproductive system and breast disorders
Vulvovaginal Dryness	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/36 (0%)		0/34 (0%)		1/30 (3.3%)
Epistaxis	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Hypoxia	2/36 (5.6%)		0/34 (0%)		1/30 (3.3%)
Pharyngolaryngeal Pain	0/36 (0%)		0/34 (0%)		2/30 (6.7%)
Skin and subcutaneous tissue disorders
Blood Blister	1/36 (2.8%)		0/34 (0%)		0/30 (0%)
Hyperhidrosis	0/36 (0%)		1/34 (2.9%)		4/30 (13.3%)
Pruritus	1/36 (2.8%)		5/34 (14.7%)		5/30 (16.7%)
Rash	1/36 (2.8%)		1/34 (2.9%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.