Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients

Study Overview
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Brief Summary
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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
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OBJECTIVES 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. 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). 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.

Official Title
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Single-dose and Multi-dose Open-label Pilot Trial of the Analgesic Efficacy and Tolerability of Intranasal Ketorolac Tromethamine (SPRIX®) in Dental Implant Surgery Patients With Postoperative Pain.

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Ketorolac Nasal Spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Key Inclusion Criteria Male or female between 18 and 64 years of age. 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. BMI between 19 and 29 kg/m2. 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. 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. In the opinion of the investigators the subject can safely tolerate ketorolac and acetaminophen. - Exclusion Criteria: Key Exclusion Criteria Require the placement of more than 3 implants or require extensive bone grafting in addition to implant placement. Need to administer anxiolytic/sedation drugs during surgery other than nitrous oxide/oxygen. Need to administer the long acting local anesthetic bupivacaine with 1:200,000 epinephrine. Implant(s) that are going to be immediately loaded on the day of surgery Females that are pregnant or breast feeding Allergies or hypersensitivity (aspirin sensitive asthma) to ketorolac, aspirin, ibuprofen, other NSAIDs, or acetaminophen. History of gastrointestinal ulcers and/or bleeding. On warfarin, dicumarol, clopidogrel or any other anticoagulant or antiplatelet therapy other than low dose (81 mg - 325 mg) aspirin. Clinically significant kidney or liver disease where the intake of NSAIDs or acetaminophen would put the subject at undo risk. Blood pressure greater than 160/95 at the time of screening or immediately before surgery. Inflammation of the nasal mucosa or upper respiratory tract infection Have ingested any analgesic agent within 48 hours of surgery. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketorolac nasal spray 31.5 mg<br>Recommended dose according to package insert in 18 - 64 year olds for moderate to moderately severe pain. | Drug: Ketorolac Nasal Spray<br>* 15.75 mg nasal spray delivery to each nostril no more than every six hours<br>* Other names: SPRIX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 20 minutes post dose | 
| 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 | 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 | VAS pain intensity score 60 minutes after dosing. | 60 minutes post dose | 
| 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 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 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 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Censored at 6 hours | 
| 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. | Self explanatory | Up to 5 days | 
| 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. | At time of depressing meaningful relief stopwatch up to 6 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute pain, dental pain, intranasal ketorolac, dental implant surgery