Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hersh, Elliot V., DMD, MS, PhD
ClinicalTrials.gov Identifier:
NCT01490931
First received: December 11, 2011
Last updated: August 6, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Postsurgical Dental Implant Surgery Pain
Drug: Ketorolac Tromethamine Nasal Spray
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Hersh, Elliot V., DMD, MS, PhD:

Primary Outcome Measures:
  • Area under the 6-hour pain intensity difference (SPID-6). [ Time Frame: 6 hour ] [ Designated as safety issue: No ]
    Area under the 6-hour Pain Intensity Difference time action curve


Secondary Outcome Measures:
  • The median onset of first perceptible, confirmed first perceptible, and meaningful pain relief of intranasal ketorolac in dental implant surgery patients [ Time Frame: Censored at 6 hours ] [ Designated as safety issue: No ]
    Data will be obtained employing the well-described double stop watch technique

  • Comparison of pain intensity scores at each time-point with the baseline pain intensity score during the initial 6-hour evaluation period. [ Time Frame: 6 hours post dose ] [ Designated as safety issue: No ]
    Pain intensity scores will be recorded by patient employing a standard 100 mm visual analog scale

  • Area under the 6-hour pain relief time action curve (TOTPAR-6) for intranasal ketorolac. [ Time Frame: 6 hours post dose ] [ Designated as safety issue: No ]
    Standard categoric pain relief score on a 0-4 scale (0=no relief, 4=complete relief) will be obtained from subject.

  • 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 ] [ Designated as safety issue: No ]
    Self explanatory

  • Mean number of days of analgesic dosing in dental implant surgery patients when employing intranasal ketorolac as their pain medication. [ Time Frame: Up to 5 days ] [ Designated as safety issue: No ]
    Self explanatory

  • 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. [ Time Frame: Up to 5 days ] [ Designated as safety issue: No ]
    Subjects will be allowed to ingest rescue medication (acetaminophen 650 mg) when and if they need it (but no more than 3000 mg per day.

  • The overall tolerability of intranasal ketorolac in dental implant surgery patients. [ Time Frame: Up to 5 days ] [ Designated as safety issue: Yes ]
    Research coordinator or investigator will record expected and unexpected adverse events during the in-house (initial 6 hours) of the study. Research subject will record adverse events during take home multi-dose phase.


Estimated Enrollment: 30
Study Start Date: November 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketorolac nasal spray 31.5 mg (SPRIX)
Recommended dose according to package insert in 18 - 64 year olds for moderate to moderately severe pain.
Drug: Ketorolac Tromethamine Nasal Spray
15.75 mg nasal spray delivery to each nostril no more than every six hours
Other Name: SPRIX

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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.

    -

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01490931

Locations
United States, Pennsylvania
University of Pennsylvania School of Dental Medicine
Philadelphia, Pennsylvania, United States, 19104-6030
Sponsors and Collaborators
Hersh, Elliot V., DMD, MS, PhD
Investigators
Principal Investigator: Elliot V Hersh, DMD, MS, PhD Univeristy of Pennsylvania School of Dental Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Hersh, Elliot V., DMD, MS, PhD
ClinicalTrials.gov Identifier: NCT01490931     History of Changes
Other Study ID Numbers: SPRIX IMPLANT 001
Study First Received: December 11, 2011
Last Updated: August 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Hersh, Elliot V., DMD, MS, PhD:
Acute pain, dental pain, ketorolac, intranasal delivery, dental implant surgery

Additional relevant MeSH terms:
Ketorolac Tromethamine
Ketorolac
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 15, 2014