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Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients

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ClinicalTrials.gov Identifier: NCT01490931
Recruitment Status : Completed
First Posted : December 13, 2011
Results First Posted : May 9, 2014
Last Update Posted : May 9, 2014
Sponsor:
Information provided by (Responsible Party):
Hersh, Elliot V., DMD, MS, PhD

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Pain
Intervention Drug: Ketorolac Nasal Spray
Enrollment 28
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.
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description

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
Period Title: Overall Study
Started 25
Completed 25
Not Completed 0
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description

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
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
Pilot Study. No power analysis performed.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
<=18 years
0
   0.0%
Between 18 and 65 years
25
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
14
  56.0%
Male
11
  44.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
pain intensity on 100 mm visual analog scale (VAS). 0=No pain 100=worst possible pain  
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 25 participants
54.4  (14.3)
1.Primary Outcome
Title Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period.
Hide Description Pain intensity scores will be recorded by patient employing a standard 100 mm visual analog scale
Time Frame 20 minutes post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
14.3  (4.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P value adjusted with Bonferroni corrections for multiple comparisons
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Comparison of Pain Intensity Scores at 40 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period.
Hide Description VAS pain intensity score at 40 minutes post-dose
Time Frame 40 minutes post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
10.1  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Comparison of Pain Intensity Scores at 60 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description VAS pain intensity score 60 minutes after dosing.
Time Frame 60 minutes post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
10.6  (1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Primary Outcome
Title Comparison of Pain Intensity Scores at 90 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description [Not Specified]
Time Frame 90 minutes post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
9.6  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Primary Outcome
Title Comparison of Pain Intensity Scores at 2 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description [Not Specified]
Time Frame 2 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
9.1  (2.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Primary Outcome
Title Comparison of Pain Intensity Scores at 3 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description [Not Specified]
Time Frame 3 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
9.6  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Primary Outcome
Title Comparison of Pain Intensity Scores at 4 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description [Not Specified]
Time Frame 4 Hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
10.0  (2.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Primary Outcome
Title Comparison of Pain Intensity Scores at 5 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description [Not Specified]
Time Frame 5 Hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
16.2  (4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Primary Outcome
Title Comparison of Pain Intensity Scores at 6 Hours With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period
Hide Description [Not Specified]
Time Frame 6 Hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Mean (Standard Error)
Unit of Measure: millimeters
19.8  (3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketorolac Nasal Spray 31.5 mg (SPRIX)
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title The Median Onset of First Perceptible Pain Relief of Intranasal Ketorolac in Dental Implant Surgery Patients
Hide Description Data will be obtained employing the well-described double stop watch technique
Time Frame Censored at 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: seconds
86
(64 to 172)
11.Secondary Outcome
Title 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.
Hide Description [Not Specified]
Time Frame Up to 5 hours after last suture is placed
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects (regardless of pain intensity) receiving one to three dental implants
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: percentage of participants
89
12.Secondary Outcome
Title Most Frequent Number of Days of Analgesic Dosing in Dental Implant Surgery Patients When Employing Intranasal Ketorolac as Their Pain Medication.
Hide Description Self explanatory
Time Frame Up to 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: days
3
13.Secondary Outcome
Title Median Onset of Meaningful Pain Relief
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description:

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
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: seconds
172
(132 to 735)
Time Frame 5 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ketorolac Nasal Spray 31.5 mg (SPRIX)
Hide Arm/Group Description

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
All-Cause Mortality
Ketorolac Nasal Spray 31.5 mg (SPRIX)
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Ketorolac Nasal Spray 31.5 mg (SPRIX)
Affected / at Risk (%) # Events
Total   0/25 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ketorolac Nasal Spray 31.5 mg (SPRIX)
Affected / at Risk (%) # Events
Total   14/25 (56.00%)    
Ear and labyrinth disorders   
Ears popping sensation * [1]  1/25 (4.00%)  1
Eye disorders   
Watery eyes *  1/25 (4.00%)  1
Gastrointestinal disorders   
Constipation *  1/25 (4.00%)  1
Nervous system disorders   
Headache * [2]  3/25 (12.00%)  3
Respiratory, thoracic and mediastinal disorders   
Nasal burning or stinging * [3]  9/25 (36.00%)  9
Throat burning * [4]  3/25 (12.00%)  3
Sneezing * [5]  2/25 (8.00%)  2
Difficulty breathing sensation * [6]  1/25 (4.00%)  1
Runny nose *  1/25 (4.00%)  1
Skin and subcutaneous tissue disorders   
Perspiring *  1/25 (4.00%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Transient immediately after dosing
[2]
3 of 25 (12%) reported headache sometime during 5 day evaluation period
[3]
Transient nasal burning on dosing in 9/25 (36%) of subjects
[4]
Transient throat burning on dosing 3/25 subjects (12%)
[5]
Sneezing on dosing 2/25 (8%)
[6]
Transient difficulty breathing sensation immediately after dosing
The major weakness of this study was its open-label design and lack of a placebo control and an active comparator drug. The study was also not powered to determine differences between the sites of implant placement and the number of implants placed.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Elliot V Hersh DMD, MS, PhD Professor of Pharmacology
Organization: Univeristy of Pennsylvania School of Dental Medicine
Phone: 215-898-9686
EMail: evhersh@pobox.upenn.edu
Publications of Results:
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.
Other Publications:
Layout table for additonal information
Responsible Party: Hersh, Elliot V., DMD, MS, PhD
ClinicalTrials.gov Identifier: NCT01490931    
Other Study ID Numbers: SPRIX IMPLANT 001
First Submitted: December 11, 2011
First Posted: December 13, 2011
Results First Submitted: February 24, 2014
Results First Posted: May 9, 2014
Last Update Posted: May 9, 2014