Postoperative Pain
Conditions
Keywords
photorefractive keratectomy, excimer laser, PRK, pain, postoperative, pregabalin
Brief summary
The purpose of this study is to compare the efficacy of pregabalin to placebo for postoperative pain control after photorefractive keratectomy.
Detailed description
Study subjects will be taken from a standard group of typical candidates for PRK surgery including active duty and DoD (Department of Defense) beneficiaries. Prior to being approached for the study, all patients will have had a previous desire for surgery and had a pre-operative evaluation indicating healthy ocular status. Patients scheduled for PRK surgery will be briefed on the purpose of the study and invited to participate at the preoperative appointment. After the consent process, patients will be randomized in a 1:1 fashion to receive either oral pregabalin 75mg twice daily or placebo for pain control, in addition to the standard care treatment of as needed Percocet and tetracaine ophthalmic drops. Subjects will be evaluated daily for 4 days post-operatively for subjective pain assessment, adverse drug events and compliance, use of concomitant medications as well as monitoring of healing time. Quality of life will be measured at baseline and post-op day 2 when the peak of pain is anticipated. Analysis will be performed to detect an approximate 10% improvement in pain scores. Secondary outcomes will include measuring healing time, quality of life and use of rescue medications.
Interventions
DRUGpregabalin
1 capsule (75 mg) by mouth twice daily starting two hours prior to surgery and continuing 4 days postoperatively.
DRUGPlacebo
1 capsule by mouth twice daily starting two hours prior to surgery and continuing 4 days postoperatively.
Sponsors
59th Medical Wing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Healthy ocular status * Stable preoperative refractive anisometropia * Consented to the PRK surgical procedure
Exclusion criteria
* Pregnant or breastfeeding * Diagnosed with autoimmune disease or diabetes * Patients with a known adverse reaction or hypersensitivity to gabapentin or pregabalin * Patients only desiring PRK on one eye * Patients with history of drug use/abuse/addiction * Patients who are on chronic pain medications * Patients currently taking anti-epileptic, antidepressant and/or anti-psychotic medications * Patients with a history of suicidality * Patients with chronic renal insufficiency (defined as estimated creatinine clearance less than 30ml/min or Scr ≥ 2.0) 10) Patients who have experienced angioedema, or have heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy | 5 days | Determine if clinical efficacy is achieved with pregabalin administered prior to PRK and continued for 5 days. This will be evaluated using the short-form McGill pain questionnaire (SF-MPQ). Primary efficacy is assessed on 100mm Visual Analog Scale (VAS); total range is 0 to 100. A score closer to zero indicates a better outcome of less pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PPI Score | 5 days | Determine if clinical efficacy is achieved with pregabalin administered prior to PRK and continued for 5 days. This will be evaluated using the short-form McGill pain questionnaire (SF-MPQ). Secondary efficacy is assessed with present pain intensity (PPI) score. Scale is 0 (no pain) to 5 (excruciating pain) |
| Total MPQ Score | 5 days | Determine if clinical efficacy is achieved with pregabalin administered prior to PRK and continued for 5 days. This will be evaluated using the short-form McGill pain questionnaire (SF-MPQ). Secondary efficacy is assessed using the Total MPQ Score. Scale minimum is 0 (no pain) to maximum of 45 (severe pain). A higher score indicates a worse outcome. |
| Quality of Life - BPI | 5 days | Determine if there was an improvement in the patient's functional health and well-being associated with pregabalin compared to standard of care as assessed by Brief Pain Inventory-short form (BPI-SF). Data was assessed on the day of surgery (Day 0) and at the expected peak of pain, postop Day 2 in the morning. Scale is minimum 0 (no pain) to maximum of 10 (pain as bad as you can imagine). A higher score indicates a worse outcome. |
| Clinical Efficacy 2 | 5 days | Determine if there was a reduction in the need for use of rescue pain medications, Percocet and tetracaine, in those subjects who received pregabalin. Total number of doses was collected. A higher number of doses required indicates a worse outcome. |
| Epithelial Healing Time | 5 days or more | Determine if there was a reduction in healing time associated with pregabalin as seen with daily slit-lamp observation. Epithelial defect was measured at post-operative day 3, 5, 7, and 9 in each eye. A higher number of days required for healing indicates a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin pregabalin: 1 capsule (75 mg) PO BID starting two hours prior to surgery and continuing 4 days postoperatively. | 67 |
| Lactose Capsule Placebo: 1 capsule PO BID starting two hours prior to surgery and continuing 4 days postoperatively. | 63 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Pregabalin | Lactose Capsule | Total |
|---|---|---|---|
| Age, Continuous | 34.6 years | 35.1 years | 34.85 years |
| Race/Ethnicity, Customized Black | 12 participants | 7 participants | 19 participants |
| Race/Ethnicity, Customized Caucasian | 38 participants | 45 participants | 83 participants |
| Race/Ethnicity, Customized Latino | 12 participants | 11 participants | 23 participants |
| Race/Ethnicity, Customized Other | 5 participants | 0 participants | 5 participants |
| Region of Enrollment United States | 67 participants | 63 participants | 130 participants |
| Sex: Female, Male Female | 37 Participants | 33 Participants | 70 Participants |
| Sex: Female, Male Male | 30 Participants | 30 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 67 | 13 / 62 |
| serious Total, serious adverse events | 0 / 67 | 0 / 62 |
Outcome results
Primary
Clinical Efficacy
Determine if clinical efficacy is achieved with pregabalin administered prior to PRK and continued for 5 days. This will be evaluated using the short-form McGill pain questionnaire (SF-MPQ). Primary efficacy is assessed on 100mm Visual Analog Scale (VAS); total range is 0 to 100. A score closer to zero indicates a better outcome of less pain.
Time frame: 5 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Clinical Efficacy | Surgery Day | 7.56 units on a scale | Standard Deviation 10.95 |
| Pregabalin | Clinical Efficacy | Postop day 2 evening | 26.14 units on a scale | Standard Deviation 22.79 |
| Pregabalin | Clinical Efficacy | Postop day 1 evening | 21.32 units on a scale | Standard Deviation 21.95 |
| Pregabalin | Clinical Efficacy | Postop day 3 morning | 8.48 units on a scale | Standard Deviation 12.84 |
| Pregabalin | Clinical Efficacy | Postop day 1 morning | 6.32 units on a scale | Standard Deviation 9.14 |
| Pregabalin | Clinical Efficacy | Postop day 3 evening | 3.48 units on a scale | Standard Deviation 6.74 |
| Pregabalin | Clinical Efficacy | Postop day 2 morning | 23.49 units on a scale | Standard Deviation 21.31 |
| Pregabalin | Clinical Efficacy | Postop day 4 morning | 1.9 units on a scale | Standard Deviation 4.56 |
| Pregabalin | Clinical Efficacy | Baseline | 0.89 units on a scale | Standard Deviation 2.51 |
| Lactose Capsule | Clinical Efficacy | Postop day 4 morning | 2.65 units on a scale | Standard Deviation 7.7 |
| Lactose Capsule | Clinical Efficacy | Baseline | 1.33 units on a scale | Standard Deviation 8.3 |
| Lactose Capsule | Clinical Efficacy | Surgery Day | 10.34 units on a scale | Standard Deviation 16.55 |
| Lactose Capsule | Clinical Efficacy | Postop day 1 morning | 10.22 units on a scale | Standard Deviation 15.27 |
| Lactose Capsule | Clinical Efficacy | Postop day 1 evening | 27.09 units on a scale | Standard Deviation 25.03 |
| Lactose Capsule | Clinical Efficacy | Postop day 2 morning | 29.27 units on a scale | Standard Deviation 25.1 |
| Lactose Capsule | Clinical Efficacy | Postop day 2 evening | 25.78 units on a scale | Standard Deviation 26.66 |
| Lactose Capsule | Clinical Efficacy | Postop day 3 morning | 8.76 units on a scale | Standard Deviation 15.66 |
| Lactose Capsule | Clinical Efficacy | Postop day 3 evening | 6.02 units on a scale | Standard Deviation 11.18 |
Comparison: This study was designed to determine if pregabalin is an effective regimen for postoperative pain control following PRK. We hypothesized that there will be at least a 10% improvement in pain after PRK using a scheduled pregabalin dosing regimen compared to placebo. A power analysis was completed to determine the number of patients necessary.p-value: 0.18ANOVA
Secondary
Clinical Efficacy 2
Determine if there was a reduction in the need for use of rescue pain medications, Percocet and tetracaine, in those subjects who received pregabalin. Total number of doses was collected. A higher number of doses required indicates a worse outcome.
Time frame: 5 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Clinical Efficacy 2 | Surgery Day | 0.81 Rescue medication doses | Standard Deviation 1.234 |
| Pregabalin | Clinical Efficacy 2 | Postop Day 1 | 1.7 Rescue medication doses | Standard Deviation 1.842 |
| Pregabalin | Clinical Efficacy 2 | Postop Day 3 | 1.7 Rescue medication doses | Standard Deviation 1.633 |
| Pregabalin | Clinical Efficacy 2 | Postop Day 4 | 0.43 Rescue medication doses | Standard Deviation 0.802 |
| Lactose Capsule | Clinical Efficacy 2 | Postop Day 4 | 0.62 Rescue medication doses | Standard Deviation 1.25 |
| Lactose Capsule | Clinical Efficacy 2 | Surgery Day | 0.94 Rescue medication doses | Standard Deviation 1.134 |
| Lactose Capsule | Clinical Efficacy 2 | Postop Day 3 | 2.56 Rescue medication doses | Standard Deviation 2.589 |
| Lactose Capsule | Clinical Efficacy 2 | Postop Day 1 | 2.44 Rescue medication doses | Standard Deviation 2.014 |
p-value: 0.311ANOVA
Secondary
Epithelial Healing Time
Determine if there was a reduction in healing time associated with pregabalin as seen with daily slit-lamp observation. Epithelial defect was measured at post-operative day 3, 5, 7, and 9 in each eye. A higher number of days required for healing indicates a worse outcome.
Time frame: 5 days or more
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Epithelial Healing Time | Days to Heal OD (Right Eye) | 3 Days | Standard Deviation 1.087 |
| Pregabalin | Epithelial Healing Time | Days to Heal OS (Left Eye) | 3.09 Days | Standard Deviation 1.164 |
| Lactose Capsule | Epithelial Healing Time | Days to Heal OD (Right Eye) | 2.9 Days | Standard Deviation 0.856 |
| Lactose Capsule | Epithelial Healing Time | Days to Heal OS (Left Eye) | 2.9 Days | Standard Deviation 0.856 |
Comparison: Days to Heal, ODp-value: 0.581t-test, 2 sided
Comparison: Days to Heal, OSp-value: 0.307t-test, 2 sided
Secondary
PPI Score
Determine if clinical efficacy is achieved with pregabalin administered prior to PRK and continued for 5 days. This will be evaluated using the short-form McGill pain questionnaire (SF-MPQ). Secondary efficacy is assessed with present pain intensity (PPI) score. Scale is 0 (no pain) to 5 (excruciating pain)
Time frame: 5 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | PPI Score | Postop day 3 morning | 0.67 score on a scale | Standard Deviation 0.77 |
| Pregabalin | PPI Score | Postop day 3 evening | 0.3 score on a scale | Standard Deviation 0.58 |
| Pregabalin | PPI Score | Postop day 2 morning | 1.43 score on a scale | Standard Deviation 0.89 |
| Pregabalin | PPI Score | Postop day 2 evening | 1.46 score on a scale | Standard Deviation 0.94 |
| Pregabalin | PPI Score | Baseline | 0.03 score on a scale | Standard Deviation 0.17 |
| Pregabalin | PPI Score | Surgery Day | 0.69 score on a scale | Standard Deviation 0.76 |
| Pregabalin | PPI Score | Postop day 1 morning | 0.67 score on a scale | Standard Deviation 0.73 |
| Pregabalin | PPI Score | Postop day 1 evening | 1.37 score on a scale | Standard Deviation 0.89 |
| Pregabalin | PPI Score | Postop day 4 morning | 0.18 score on a scale | Standard Deviation 0.46 |
| Lactose Capsule | PPI Score | Postop day 1 evening | 1.62 score on a scale | Standard Deviation 1.24 |
| Lactose Capsule | PPI Score | Postop day 3 morning | 0.68 score on a scale | Standard Deviation 0.93 |
| Lactose Capsule | PPI Score | Surgery Day | 0.84 score on a scale | Standard Deviation 0.79 |
| Lactose Capsule | PPI Score | Postop day 2 evening | 1.48 score on a scale | Standard Deviation 1.05 |
| Lactose Capsule | PPI Score | Postop day 3 evening | 0.48 score on a scale | Standard Deviation 0.78 |
| Lactose Capsule | PPI Score | Postop day 2 morning | 1.62 score on a scale | Standard Deviation 0.99 |
| Lactose Capsule | PPI Score | Postop day 1 morning | 0.89 score on a scale | Standard Deviation 0.88 |
| Lactose Capsule | PPI Score | Postop day 4 morning | 0.22 score on a scale | Standard Deviation 0.66 |
| Lactose Capsule | PPI Score | Baseline | 0.03 score on a scale | Standard Deviation 0.25 |
p-value: 0.207ANOVA
Secondary
Quality of Life - BPI
Determine if there was an improvement in the patient's functional health and well-being associated with pregabalin compared to standard of care as assessed by Brief Pain Inventory-short form (BPI-SF). Data was assessed on the day of surgery (Day 0) and at the expected peak of pain, postop Day 2 in the morning. Scale is minimum 0 (no pain) to maximum of 10 (pain as bad as you can imagine). A higher score indicates a worse outcome.
Time frame: 5 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Quality of Life - BPI | Pain at its Worst, Day0 | 0.51 score on a scale | Standard Deviation 1.02 |
| Pregabalin | Quality of Life - BPI | Pain at its Worst, Day2 | 3.76 score on a scale | Standard Deviation 2.511 |
| Pregabalin | Quality of Life - BPI | Pain at its Least, Day 0 | 0.13 score on a scale | Standard Deviation 0.519 |
| Pregabalin | Quality of Life - BPI | Pain at its least, Day2 | 1.31 score on a scale | Standard Deviation 1.588 |
| Pregabalin | Quality of Life - BPI | Avg Pain, Day0 | 0.37 score on a scale | Standard Deviation 0.693 |
| Pregabalin | Quality of Life - BPI | Avg Pain, Day2 | 2.28 score on a scale | Standard Deviation 1.929 |
| Pregabalin | Quality of Life - BPI | Pain Interference, Day0 | 0.13 score on a scale | Standard Deviation 0.484 |
| Pregabalin | Quality of Life - BPI | Pain Interference, Day2 | 2.56 score on a scale | Standard Deviation 2.161 |
| Lactose Capsule | Quality of Life - BPI | Pain Interference, Day2 | 3.5 score on a scale | Standard Deviation 2.832 |
| Lactose Capsule | Quality of Life - BPI | Pain at its Worst, Day0 | 0.24 score on a scale | Standard Deviation 1.011 |
| Lactose Capsule | Quality of Life - BPI | Avg Pain, Day0 | 0.33 score on a scale | Standard Deviation 1.122 |
| Lactose Capsule | Quality of Life - BPI | Pain at its Worst, Day2 | 4.67 score on a scale | Standard Deviation 2.84 |
| Lactose Capsule | Quality of Life - BPI | Pain Interference, Day0 | 0.13 score on a scale | Standard Deviation 0.742 |
| Lactose Capsule | Quality of Life - BPI | Pain at its Least, Day 0 | 0.08 score on a scale | Standard Deviation 0.517 |
| Lactose Capsule | Quality of Life - BPI | Avg Pain, Day2 | 3.03 score on a scale | Standard Deviation 2.155 |
| Lactose Capsule | Quality of Life - BPI | Pain at its least, Day2 | 1.48 score on a scale | Standard Deviation 1.83 |
p-value: 0.223ANOVA
Secondary
Total MPQ Score
Determine if clinical efficacy is achieved with pregabalin administered prior to PRK and continued for 5 days. This will be evaluated using the short-form McGill pain questionnaire (SF-MPQ). Secondary efficacy is assessed using the Total MPQ Score. Scale minimum is 0 (no pain) to maximum of 45 (severe pain). A higher score indicates a worse outcome.
Time frame: 5 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Total MPQ Score | Surgery Day | 1.85 score on a scale | Standard Deviation 2.28 |
| Pregabalin | Total MPQ Score | Postop day 2 evening | 4.87 score on a scale | Standard Deviation 4.1 |
| Pregabalin | Total MPQ Score | Postop day 1 evening | 4.6 score on a scale | Standard Deviation 5.07 |
| Pregabalin | Total MPQ Score | Postop day 3 morning | 1.7 score on a scale | Standard Deviation 2.34 |
| Pregabalin | Total MPQ Score | Postop day 1 morning | 1.79 score on a scale | Standard Deviation 2.16 |
| Pregabalin | Total MPQ Score | Postop day 3 evening | 0.97 score on a scale | Standard Deviation 2.02 |
| Pregabalin | Total MPQ Score | Postop day 2 morning | 4.67 score on a scale | Standard Deviation 3.9 |
| Pregabalin | Total MPQ Score | Postop day 4 morning | 0.6 score on a scale | Standard Deviation 1.35 |
| Pregabalin | Total MPQ Score | Baseline | 0.15 score on a scale | Standard Deviation 0.47 |
| Lactose Capsule | Total MPQ Score | Postop day 4 morning | 0.39 score on a scale | Standard Deviation 1.22 |
| Lactose Capsule | Total MPQ Score | Baseline | 0.16 score on a scale | Standard Deviation 0.85 |
| Lactose Capsule | Total MPQ Score | Surgery Day | 2.18 score on a scale | Standard Deviation 3.01 |
| Lactose Capsule | Total MPQ Score | Postop day 1 morning | 2.16 score on a scale | Standard Deviation 2.36 |
| Lactose Capsule | Total MPQ Score | Postop day 1 evening | 5.37 score on a scale | Standard Deviation 6.67 |
| Lactose Capsule | Total MPQ Score | Postop day 2 morning | 5.61 score on a scale | Standard Deviation 6.5 |
| Lactose Capsule | Total MPQ Score | Postop day 2 evening | 5.68 score on a scale | Standard Deviation 7.54 |
| Lactose Capsule | Total MPQ Score | Postop day 3 morning | 2.9 score on a scale | Standard Deviation 6.21 |
| Lactose Capsule | Total MPQ Score | Postop day 3 evening | 1.16 score on a scale | Standard Deviation 1.72 |
p-value: 0.283ANOVA