Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients

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.

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.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Ketorolac Nasal Spray

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-6030
      • University of Pennsylvania School of Dental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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Exclusion Criteria:

Key Exclusion Criteria

1. Require the placement of more than 3 implants or require extensive bone grafting in addition to implant placement.
2. Need to administer anxiolytic/sedation drugs during surgery other than nitrous oxide/oxygen.
3. Need to administer the long acting local anesthetic bupivacaine with 1:200,000 epinephrine.
4. Implant(s) that are going to be immediately loaded on the day of surgery
5. Females that are pregnant or breast feeding
6. Allergies or hypersensitivity (aspirin sensitive asthma) to ketorolac, aspirin, ibuprofen, other NSAIDs, or acetaminophen.
7. History of gastrointestinal ulcers and/or bleeding.
8. On warfarin, dicumarol, clopidogrel or any other anticoagulant or antiplatelet therapy other than low dose (81 mg - 325 mg) aspirin.
9. Clinically significant kidney or liver disease where the intake of NSAIDs or acetaminophen would put the subject at undo risk.
10. Blood pressure greater than 160/95 at the time of screening or immediately before surgery.
11. Inflammation of the nasal mucosa or upper respiratory tract infection

12. Have ingested any analgesic agent within 48 hours of surgery.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Hersh, Elliot V., DMD, MS, PhD
• Investigators: Principal Investigator: Elliot V Hersh, DMD, MS, PhD, Univeristy of Pennsylvania School of Dental Medicine

Publications and helpful links

General Publications

• Al-Khabbaz AK, Griffin TJ, Al-Shammari KF. Assessment of pain associated with the surgical placement of dental implants. J Periodontol. 2007 Feb;78(2):239-46. doi: 10.1902/jop.2007.060032.
• Hersh EV, Levin LM, Adamson D, Christensen S, Kiersch TA, Noveck R, Watson G 2nd, Lyon JA. Dose-ranging analgesic study of Prosorb diclofenac potassium in postsurgical dental pain. Clin Ther. 2004 Aug;26(8):1215-27. doi: 10.1016/s0149-2918(04)80033-x.
• Bockow R, Korostoff J, Pinto A, Hutcheson M, Secreto SA, Bodner L, Hersh EV. Characterization and treatment of postsurgical dental implant pain employing intranasal ketorolac. Compend Contin Educ Dent. 2013 Sep;34(8):570-6.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: December 11, 2011
• First Submitted That Met QC Criteria: December 11, 2011
• First Posted (Estimate): December 13, 2011

Study Record Updates

• Last Update Posted (Estimate): May 9, 2014
• Last Update Submitted That Met QC Criteria: April 11, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: acute pain; dental pain; intranasal ketorolac; dental implant surgery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac
• Other Study ID Numbers: SPRIX IMPLANT 001