Trial Outcomes & Findings for OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients (NCT NCT04694300)
NCT ID: NCT04694300
Last Updated: 2024-05-16
Results Overview
Median maximum pain intensity scores where 0 = no pain and 10 = worst possible pain
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
30 participants
Primary outcome timeframe
Up to 6 hours
Results posted on
2024-05-16
Participant Flow
Subjects scheduled in University of Pennsylvania School of Dental Medicine Periodontics Clinic to receive the surgical placement of one or two dental implants.
Participant milestones
| Measure |
Naproxen Sodium
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later. Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients
Baseline characteristics by cohort
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later. Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.8 years
STANDARD_DEVIATION 14.9 • n=99 Participants
|
45.5 years
STANDARD_DEVIATION 14.2 • n=107 Participants
|
46.2 years
STANDARD_DEVIATION 14.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Body Mass Index (BMI)
|
25.2 BMI (kg/m^2)
STANDARD_DEVIATION 3.6 • n=99 Participants
|
26.8 BMI (kg/m^2)
STANDARD_DEVIATION 4.3 • n=107 Participants
|
26.0 BMI (kg/m^2)
STANDARD_DEVIATION 4.0 • n=206 Participants
|
|
Length of Surgery
|
71.1 Minutes
STANDARD_DEVIATION 35.8 • n=99 Participants
|
85.5 Minutes
STANDARD_DEVIATION 30.6 • n=107 Participants
|
78.4 Minutes
STANDARD_DEVIATION 33.7 • n=206 Participants
|
PRIMARY outcome
Timeframe: Up to 6 hoursPopulation: Medium Greatest Pain Intensity Scores from 0-6 hours Following Dosing With Naproxen Sodium or Acetaminophen
Median maximum pain intensity scores where 0 = no pain and 10 = worst possible pain
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Pain Intensity Scores on Numeric Pain Intensity Scale 0-6 Hours
|
1 score on a scale
Interval 0.0 to 2.0
|
3 score on a scale
Interval 2.0 to 7.0
|
PRIMARY outcome
Timeframe: 6-72 hours Post initial DosePopulation: Mean Pain Intensity Scores from 6-72 hours Following Around-the-Clock Dosing With Naproxen Sodium or Acetaminophen
Pain intensity scores where 0 = no pain and 10 = worst possible pain
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Pain Intensity Scores From 6 Through 72 Hours (Multi-dose Phase)
|
0.3 units on pain intensity scale
Interval 0.0 to 0.6
|
1.7 units on pain intensity scale
Interval 0.3 to 3.2
|
PRIMARY outcome
Timeframe: 6 hoursPlasma IL-6 concentrations 6 hours after treatment measured by ELISA
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Peak Plasma IL-6 Concentrations
|
6.5 pg/ml
Interval 6.1 to 13.4
|
12.1 pg/ml
Interval 6.7 to 30.0
|
PRIMARY outcome
Timeframe: 6 hours post dosePercent change in plasma IL-6 levels at 6 hours after treatment relative to baseline
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Plasma IL-6 Change From Baseline
|
276.9 percentage change from baseline
Interval 181.3 to 348.4
|
519.1 percentage change from baseline
Interval 262.6 to 1091.0
|
SECONDARY outcome
Timeframe: 0-6 hoursPopulation: Number of patients in each treatment group requiring opioid rescue medication (tramadol) during inpatient phase (0-6 hours)
Number of patients requiring opioid rescue medication (tramadol) during inpatient phase (0-6 hours) in each treatment group
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Rescue Analgesic Use
|
0 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 6-72 hoursNumber of patients requiring opioid rescue medication during outpatient phase in both treatment groups
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Rescue Medication Use Outpatient Phase (6-72 Hours)
|
2 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 24 hours post-doseLevels of IL-1β in gingival crevicular fluid measured at 24 hours after treatment
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Peak GCF IL-1β Levels
|
263 pg/ml
Interval 110.0 to 1293.0
|
456 pg/ml
Interval 243.0 to 1590.0
|
SECONDARY outcome
Timeframe: 6 hours post doseCyclooxygenase (COX)-1 activity was evaluated ex vivo by quantifying serum thromboxane B2 levels
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
COX-1 Activity Percent of Baseline (Pre-surgery)
|
3.7 percentage of baseline blood levels
Interval 2.8 to 11.3
|
77.4 percentage of baseline blood levels
Interval 44.2 to 84.0
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Patient in each group surgically receiving one or two implants
COX-2 activity was evaluated ex vivo by quantifying plasma prostaglandin (PG)E2 levels following lipopolysaccharide (LPS) stimulation in whole blood,
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
COX-2 Activity
|
48.4 percentage of baseline blood levels
Interval 20.3 to 113.7
|
52.4 percentage of baseline blood levels
Interval 27.7 to 146.3
|
SECONDARY outcome
Timeframe: 24 hours post-doseLevels of IL-8 in gingival crevicular fluid measured at 24 hours after treatment
Outcome measures
| Measure |
Naproxen Sodium
n=15 Participants
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 Participants
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
Peak GCF IL-8levels
|
2962 pg/ml
Interval 657.0 to 7976.0
|
5729 pg/ml
Interval 1972.0 to 9119.0
|
Adverse Events
Naproxen Sodium
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Acetaminophen
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Naproxen Sodium
n=15 participants at risk
Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)
Naproxen: 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
Acetaminophen
n=15 participants at risk
Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)
Acetaminophen: 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.
Tramadol: 50 mg by mouth every 6 hours as needed for pain
|
|---|---|---|
|
General disorders
Headache
|
6.7%
1/15 • Number of events 1 • One week
Does not differ from clinicaltrials.gov
|
0.00%
0/15 • One week
Does not differ from clinicaltrials.gov
|
|
Psychiatric disorders
Agitation
|
0.00%
0/15 • One week
Does not differ from clinicaltrials.gov
|
6.7%
1/15 • Number of events 1 • One week
Does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/15 • One week
Does not differ from clinicaltrials.gov
|
13.3%
2/15 • Number of events 2 • One week
Does not differ from clinicaltrials.gov
|
|
Gastrointestinal disorders
emesis
|
0.00%
0/15 • One week
Does not differ from clinicaltrials.gov
|
13.3%
2/15 • Number of events 2 • One week
Does not differ from clinicaltrials.gov
|
Additional Information
Elliot V Hersh DMD, MS, PhD. Professor of Oral Surgery and Pharmacology
University of Pennsylvania School of Dental Medicine
Phone: 215-898-9686
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place