Acute Pain
Conditions
Keywords
Primary, unilateral, first metatarsal bunionectomy with osteotomy
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.
Interventions
DRUGpregabalin
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.
DRUGnaproxen 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.
DRUGComparator: 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.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Recruitment details
First Patient Entered: 25 July 2007 Last Patient Last Visit: 28 January 2008 1 site
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin 300 mg 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. | 32 |
| Naproxen Sodium 550 mg 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. | 29 |
| Placebo 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. | 28 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Dosing Error | 1 | 0 | 0 |
| Overall Study | Early Termination | 0 | 1 | 1 |
| Overall Study | Incomplete Data | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | Pregabalin 300 mg | Naproxen Sodium 550 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 40.3 years STANDARD_DEVIATION 14.1 | 40.6 years STANDARD_DEVIATION 13.5 | 38.8 years STANDARD_DEVIATION 11.6 | 39.9 years STANDARD_DEVIATION 13.1 |
| Body Weight | 72.3 Kilograms STANDARD_DEVIATION 18.1 | 76.7 Kilograms STANDARD_DEVIATION 17.2 | 77.2 Kilograms STANDARD_DEVIATION 16.9 | 75.3 Kilograms STANDARD_DEVIATION 17.4 |
| Lidocaine Use | 15.0 Milliliters STANDARD_DEVIATION 2.3 | 15.9 Milliliters STANDARD_DEVIATION 2.7 | 14.6 Milliliters STANDARD_DEVIATION 1.6 | 15.2 Milliliters STANDARD_DEVIATION 2.2 |
| Propofol Use | 348.4 Milligrams STANDARD_DEVIATION 132.9 | 364.5 Milligrams STANDARD_DEVIATION 122.8 | 353.9 Milligrams STANDARD_DEVIATION 105.8 | 355.4 Milligrams STANDARD_DEVIATION 121.1 |
| Sex: Female, Male Female | 27 Participants | 23 Participants | 23 Participants | 73 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 36 | 19 / 34 | 25 / 30 |
| serious Total, serious adverse events | 0 / 36 | 0 / 34 | 0 / 30 |
Outcome results
Primary
Total Patient Controlled Analgesic (PCA) Hydromorphone Consumption Over the 24 Hours Post-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.
Time frame: First 24 hours following surgery
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Total Patient Controlled Analgesic (PCA) Hydromorphone Consumption Over the 24 Hours Post-surgery | 2.94 milligrams |
| Naproxen Sodium 550 mg | Total Patient Controlled Analgesic (PCA) Hydromorphone Consumption Over the 24 Hours Post-surgery | 2.07 milligrams |
| Placebo | Total Patient Controlled Analgesic (PCA) Hydromorphone Consumption Over the 24 Hours Post-surgery | 5.96 milligrams |
p-value: 0.00597.8% CI: [-73.6, -8]ANOVA
p-value: 0.000197.8% CI: [-81.7, -34.6]ANOVA
Secondary
Time to First Request of PCA Hydromorphone
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin 300 mg | Time to First Request of PCA Hydromorphone | 7.3 Hours |
| Naproxen Sodium 550 mg | Time to First Request of PCA Hydromorphone | 9.1 Hours |
| Placebo | Time to First Request of PCA Hydromorphone | 5.8 Hours |
p-value: 0.00495% CI: [0.183, 2.95]Log Rank
p-value: <0.00195% CI: [1.77, 6.72]Log Rank