Acute PainPhase 4NCT01490931
Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients
A Phase 4 study testing Ketorolac Nasal Spray in people with Acute Pain, run by Hersh, Elliot V., DMD, MS, PhD at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Acute Pain
- What is being tested?
- Ketorolac Nasal Spray
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Aug 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
- -
Who cannot join
- 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.
Show all 13Show fewer
- 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.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania School of Dental Medicine
Philadelphia, Pennsylvania, 19104-6030
About this study
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.
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.
Read the detailed description
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.
- Conditions
- Acute Pain
- Being tested
- Ketorolac Nasal Spray
- Keywords
- acute pain, dental pain, intranasal ketorolac, dental implant surgery
- Medical subject headings
- Acute Pain, Toothache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketorolac Nasal SprayDrug
Also called SPRIX
15.75 mg nasal spray delivery to each nostril no more than every six hours
| Study group | Role | What they receive |
|---|---|---|
| Ketorolac nasal spray 31.5 mg | Experimental | Recommended dose according to package insert in 18 - 64 year olds for moderate to moderately severe pain. Receives: Drug: Ketorolac Nasal Spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 2 Hours
Comparison of Pain Intensity Scores at 3 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Measured: 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
Measured: 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
Measured: 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
Measured: 6 Hours post-dose
Secondary outcomes (4)
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
Measured: 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.
Measured: 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
Measured: 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.
Measured: At time of depressing meaningful relief stopwatch up to 6 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hersh, Elliot V., DMD, MS, PhD
- Responsible party
- Sponsor
- Investigators
- Elliot V Hersh, DMD, MS, PhD, Principal investigator, Univeristy of Pennsylvania School of Dental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490931
- Sponsor's protocol ID
- SPRIX IMPLANT 001
- Status last verified
- Apr 2014
- First submitted
- 11 Dec 2011
- Last updated
- 9 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 17274712Hersh 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.
PubMed 15476903Bockow 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.
PubMed 24564610
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01490931
- Acronym / sponsor ID
- SPRIX IMPLANT 001
- Conditions
- Acute Pain
- Keywords
- acute pain, dental pain, intranasal ketorolac, dental implant surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Hersh, Elliot V., DMD, MS, PhD
- Study start
- Nov 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 13 Dec 2011 (estimated)
- Results
- Posted 9 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketorolac nasal spray 31.5 mg | Experimental | Drug: Ketorolac Nasal SprayRecommended dose according to package insert in 18 - 64 year olds for moderate to moderately severe pain. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketorolac Nasal SprayAlso: SPRIX15.75 mg nasal spray delivery to each nostril no more than every six hours | Drug | Ketorolac nasal spray 31.5 mg |
Primary outcome
Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period.
Time frame: 20 minutes post dose
Pain intensity scores will be recorded by patient employing a standard 100 mm visual analog scale
Comparison of Pain Intensity Scores at 40 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 2 Hours
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
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
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
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
4 secondary outcomes
The Median Onset of First Perceptible Pain Relief of Intranasal Ketorolac in Dental Implant Surgery Patients
Time frame: 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.
Time frame: 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.
Time frame: Up to 5 days
Median Onset of Meaningful Pain Relief
Time frame: At time of depressing meaningful relief stopwatch up to 6 hours.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17274712Al-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.
- Background: PubMed 15476903Hersh 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.
- Results publication: PubMed 24564610Bockow 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elliot V Hersh, DMD, MS, PhD principal investigator
Univeristy of Pennsylvania School of Dental Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketorolac Nasal Spray in people with Acute Pain, run by Hersh, Elliot V., DMD, MS, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period. (time frame: 20 minutes post dose). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01490931, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2014.