Acute Pain
Conditions
Keywords
acute pain, dental pain, intranasal ketorolac, dental implant surgery
Brief summary
The surgical placement of dental implants is presently a common procedure performed by oral surgeons, periodontists, and general dentists. The surgery can be performed under local anesthesia and involves the incision of soft tissue to expose the underlying bone, preparation of the implant site using a specialized surgical drill, and.screwing the implant into bone using a specialized headpiece. Dental implant patients experience postoperative pain yet there are no studies in the literature which have evaluated the efficacy of analgesics in this patient population. The current pilot study will evaluate the analgesic effects and tolerability of a recently FDA-approved analgesic formulation of intranasal ketorolac (SPRIX®) in 25 patients who have 1 - 3 dental implants surgically placed. Patients will self administer the ketorolac nasal spray (one spray in each nostril, 31.5 mg total dose) when their postoperative pain reaches at least a moderate severity. Pain intensity and pain relief scores will then be recorded every 20 minutes for the first hour, at 1.5 and 2 hours and then hourly through 6 hours on a validated analgesic diary. Side effects will be recorded when and if they occur. Patients will then transition to a multi-dose phase where they will be allowed to dose with ketorolac as indicated in the package insert (up to 4 times per day for 5 days). Patients will record the time of each dose, a daily assessment of overall efficacy and side effects, and the use of any rescue medication (acetaminophen 650 mg) on a take home diary.
Detailed description
OBJECTIVES 1. Overall Objectives The purpose of this pilot study will be to evaluate the analgesic efficacy and tolerability of intranasal ketorolac employed at doses and dosing intervals stated in the package insert in patients experiencing moderate to severe pain following dental implant surgery. This open label study should provide data that will allow us to estimate sample size for a future placebo-controlled trial in the dental implant surgery population. 2. Primary Outcome Variable(s) To determine if intranasal ketorolac significantly reduces pain intensity scores when compared to baseline pain intensity as measured by the area under the 6-hour pain intensity difference (SPID-6). 3. Secondary Outcome Variable(s) To determine the median onset of first perceptible, confirmed first perceptible, and meaningful pain relief of intranasal ketorolac in dental implant surgery patients. To compare mean post-dose pain intensity scores at each time-point with the baseline pain intensity score during the initial 6-hour evaluation period. To calculate the area under the 6-hour pain relief time action curve (TOTPAR-6) for intranasal ketorolac. To calculate the percentage of subjects who reach a level of at least moderate pain by achieving a score of at least 40 mm on a 100 mm visual analog scale within 5 hours after the completion of surgery. To determine the mean number of days of analgesic dosing in dental implant surgery patients when employing intranasal ketorolac as their pain medication. To determine the number of patients taking rescue medication (acetaminophen 650 mg) and the mean number of rescue medication doses taken in dental implant surgery patients when employing intranasal ketorolac as their pain medication. To determine the overall tolerability of intranasal ketorolac in dental implant surgery patients.
Interventions
DRUGKetorolac Nasal Spray
15.75 mg nasal spray delivery to each nostril no more than every six hours
Sponsors
Hersh, Elliot V., DMD, MS, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. Male or female between 18 and 64 years of age. 2. Must sign informed consent prior to initiation of any study procedures. The subject must be able to understand and agree to cooperate with study requirements. 3. BMI between 19 and 29 kg/m2. 4. Must require the surgical placement of 1 - 3 dental implants that are being placed in a one or two stage non-immediately loaded surgical procedure employing 2% lidocaine and/or 4% articaine with epinephrine and/or 3% mepivacaine plain for local anesthesia. 5. Females of child-bearing potential must have a negative urine pregnancy test at screening and immediately prior to the initiation of dental implant surgery and must have been using adequate means of birth control (abstinence, oral contraceptive steroids, intrauterine device (IUD), etc.) for at least one month prior to study entry and during the study. 6. In the opinion of the investigators the subject can safely tolerate ketorolac and acetaminophen. \-
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Pain Intensity Scores at 3 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 3 hours post-dose | — |
| Comparison of Pain Intensity Scores at 40 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period. | 40 minutes post dose | VAS pain intensity score at 40 minutes post-dose |
| Comparison of Pain Intensity Scores at 60 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 60 minutes post dose | VAS pain intensity score 60 minutes after dosing. |
| Comparison of Pain Intensity Scores at 90 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 90 minutes post-dose | — |
| Comparison of Pain Intensity Scores at 2 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 2 Hours | — |
| Comparison of Pain Intensity Scores at 5 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 5 Hours post-dose | — |
| Comparison of Pain Intensity Scores at 6 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 6 Hours post-dose | — |
| Comparison of Pain Intensity Scores at 4 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 4 Hours post-dose | — |
| Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period. | 20 minutes post dose | Pain intensity scores will be recorded by patient employing a standard 100 mm visual analog scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Reach a Level of at Least Moderate Pain by Achieving a Score of at Least 40 mm on a 100 mm Visual Analog Scale Within 5 Hours After the Completion of Surgery. | Up to 5 hours after last suture is placed | — |
| Most Frequent Number of Days of Analgesic Dosing in Dental Implant Surgery Patients When Employing Intranasal Ketorolac as Their Pain Medication. | Up to 5 days | Self explanatory |
| Median Onset of Meaningful Pain Relief | At time of depressing meaningful relief stopwatch up to 6 hours. | Measure obtained using recognized double-stop watch technique. Patient is asked to depress the second stop watch when pain relief is meaningful to them. Each patient decides what meaningful relief is for them. |
| The Median Onset of First Perceptible Pain Relief of Intranasal Ketorolac in Dental Implant Surgery Patients | Censored at 6 hours | Data will be obtained employing the well-described double stop watch technique |
Countries
United States
Participant flow
Recruitment details
Consecutive patients in PENN periodontal clinic or faculty practice requiring 1 to 3 dental implants employing lidocaine with epinephrine for anesthesia without significant bone augmentation
Pre-assignment details
Subjects not experiencing moderate pain (at least 40 mm on the pain intensity VAS and moderate or severe pain on the 4-point categorical scale) within 4 hours of surgery were not dosed with ketorolac. Of the 28 enrolled subjects, 25 (89%) achieved at least moderate pain and were dosed.
Participants by arm
| Arm | Count |
|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) Recommended dose according to package insert in 18 - 64 year olds for moderate to moderately severe pain.
Ketorolac Tromethamine Nasal Spray: 15.75 mg nasal spray delivery to each nostril no more than every six hours | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Ketorolac Nasal Spray 31.5 mg (SPRIX) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| pain intensity on 100 mm visual analog scale (VAS). 0=No pain 100=worst possible pain | 54.4 units on a scale STANDARD_DEVIATION 14.3 |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period.
Pain intensity scores will be recorded by patient employing a standard 100 mm visual analog scale
Time frame: 20 minutes post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period. | 14.3 millimeters | Standard Error 4.1 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 2 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Time frame: 2 Hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 2 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 9.1 millimeters | Standard Error 2 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 3 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Time frame: 3 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 3 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 9.6 millimeters | Standard Error 2.2 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <1t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 40 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period.
VAS pain intensity score at 40 minutes post-dose
Time frame: 40 minutes post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 40 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period. | 10.1 millimeters | Standard Error 2.2 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 4 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Time frame: 4 Hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 4 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 10.0 millimeters | Standard Error 2 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 5 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Time frame: 5 Hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 5 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 16.2 millimeters | Standard Error 4.3 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 60 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
VAS pain intensity score 60 minutes after dosing.
Time frame: 60 minutes post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 60 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 10.6 millimeters | Standard Error 1.8 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 6 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Time frame: 6 Hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 6 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 19.8 millimeters | Standard Error 3.7 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Primary
Comparison of Pain Intensity Scores at 90 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Time frame: 90 minutes post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Comparison of Pain Intensity Scores at 90 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period | 9.6 millimeters | Standard Error 2.2 |
Comparison: Changes in pain intensity on the VAS were statistically compared to baseline pain utilizing paired t tests with Bonferroni corrections for multiple comparisons. The median onsets of first perceptible and meaningful relief (with 95% confidence intervals) were calculated and then used to construct Kaplan-Meier Curves of the distribution of pain relief times.p-value: <0.0001t-test, 2 sided
Secondary
Median Onset of Meaningful Pain Relief
Measure obtained using recognized double-stop watch technique. Patient is asked to depress the second stop watch when pain relief is meaningful to them. Each patient decides what meaningful relief is for them.
Time frame: At time of depressing meaningful relief stopwatch up to 6 hours.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Median Onset of Meaningful Pain Relief | 172 seconds |
Secondary
Most Frequent Number of Days of Analgesic Dosing in Dental Implant Surgery Patients When Employing Intranasal Ketorolac as Their Pain Medication.
Self explanatory
Time frame: Up to 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Most Frequent Number of Days of Analgesic Dosing in Dental Implant Surgery Patients When Employing Intranasal Ketorolac as Their Pain Medication. | 3 days |
Secondary
Percentage of Subjects Who Reach a Level of at Least Moderate Pain by Achieving a Score of at Least 40 mm on a 100 mm Visual Analog Scale Within 5 Hours After the Completion of Surgery.
Time frame: Up to 5 hours after last suture is placed
Population: All subjects (regardless of pain intensity) receiving one to three dental implants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | Percentage of Subjects Who Reach a Level of at Least Moderate Pain by Achieving a Score of at Least 40 mm on a 100 mm Visual Analog Scale Within 5 Hours After the Completion of Surgery. | 89 percentage of participants |
Secondary
The Median Onset of First Perceptible Pain Relief of Intranasal Ketorolac in Dental Implant Surgery Patients
Data will be obtained employing the well-described double stop watch technique
Time frame: Censored at 6 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketorolac Nasal Spray 31.5 mg (SPRIX) | The Median Onset of First Perceptible Pain Relief of Intranasal Ketorolac in Dental Implant Surgery Patients | 86 seconds |