Trial Outcomes & Findings for AUGMENTIN™ in Dental Infections (NCT NCT02141217)

NCT ID: NCT02141217

Last Updated: 2017-09-25

Results Overview

Clinical success is defined as the achievement of cure or improvement in signs and symptoms of odontogenic infections. Cure is defined as the complete resolution of signs and symptoms of infection present at baseline, such that no additional antimicrobial therapy is required. Improvement is defined as the resolution of fever (if present at baseline), \>70% reduction in swelling and pain and improvement in other signs and symptoms such that no additional antimicrobial therapy is required. Visual Analogue Scale (VAS) is used to measure the amount of pain and swelling that a participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no pain and 10 indicates worst possible pain.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

472 participants

Primary outcome timeframe

Day 5 or Day 7 [End of treatment]

Results posted on

2017-09-25

Participant Flow

A total of 510 participants (par.) were screened; 472 were randomized to receive one of the two study treatments. Of the 472 par.; 235 par. were randomized to the amoxicillin + clavulanic acid (amx+clv) arm and 237 par. to the clindamycin (clin) arm.

Amongst the randomized par., 236 par. received amx+clv and 235 par. received clin as 2 par. randomized to the clin arm incorrectly received amx+clv and 1 par. randomized to amx+clv arm confirmed not consuming even a single dose of study drug.

Participant milestones

Participant milestones
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
Participants received amoxicillin 875 milligrams (mg) plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Overall Study
STARTED
234
237
Overall Study
ITT Population-Randomized Treatment Arm
234
237
Overall Study
ITT Population-Actual Treatment Received
236
235
Overall Study
COMPLETED
223
229
Overall Study
NOT COMPLETED
11
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
Participants received amoxicillin 875 milligrams (mg) plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Overall Study
Adverse Event
1
2
Overall Study
Protocol Violation
1
4
Overall Study
Withdrawal by Subject
6
0
Overall Study
Lost to Follow-up
1
1
Overall Study
Physician Decision
1
0
Overall Study
Surgical Intervention
1
1

Baseline Characteristics

AUGMENTIN™ in Dental Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=234 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=237 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Total
n=471 Participants
Total of all reporting groups
Age, Continuous
33.1 Years
STANDARD_DEVIATION 12.8 • n=5 Participants
32.6 Years
STANDARD_DEVIATION 12.0 • n=7 Participants
32.9 Years
STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male
Female
135 Participants
n=5 Participants
143 Participants
n=7 Participants
278 Participants
n=5 Participants
Sex: Female, Male
Male
99 Participants
n=5 Participants
94 Participants
n=7 Participants
193 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian-Central/South Asian Heritage
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian-East Asian Heritage
1 Participants
n=5 Participants
4 Participants
n=7 Participants
5 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian-South East Asian Heritage
233 Participants
n=5 Participants
232 Participants
n=7 Participants
465 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 5 or Day 7 [End of treatment]

Population: Per-Protocol (PP) Population: all participants in the Intent-to-Treat (ITT) Population (defined as all randomized participants who received at least one dose of study medication) who were without major protocol violations and had end of treatment clinical response assessment available.

Clinical success is defined as the achievement of cure or improvement in signs and symptoms of odontogenic infections. Cure is defined as the complete resolution of signs and symptoms of infection present at baseline, such that no additional antimicrobial therapy is required. Improvement is defined as the resolution of fever (if present at baseline), \>70% reduction in swelling and pain and improvement in other signs and symptoms such that no additional antimicrobial therapy is required. Visual Analogue Scale (VAS) is used to measure the amount of pain and swelling that a participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no pain and 10 indicates worst possible pain.

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=211 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=203 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Percentage of Participants Achieving Clinical Success (Cure or Improvement) Considering Clinical Judgment of the Investigator at the End of Treatment (Day 5 or Day 7)
88.2 Percentage of participants
89.7 Percentage of participants

PRIMARY outcome

Timeframe: Day 5 or Day 7 [End of treatment]

Population: Intent-To-Treat-Efficacy (ITT-E) Population: all participants in the ITT participants who had at least one post-Baseline assessment of clinical success response (clinical response based on assessment on odontogenic infection and VAS Score).

Clinical success is defined as the achievement of cure or improvement in signs and symptoms of odontogenic infections. Cure is defined as the complete resolution of signs and symptoms of infection present at baseline, such that no additional antimicrobial therapy is required. Improvement is defined as the resolution of fever (if present at baseline), \>70% reduction in swelling and pain and improvement in other signs and symptoms such that no additional antimicrobial therapy is required. Visual Analogue Scale (VAS) is used to measure the amount of pain and swelling that a participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no pain and 10 indicates worst possible pain.

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=228 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=235 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Percentage of Participants Achieving Clinical Success (Cure or Improvement) Considering Clinical Judgment of the Investigator at the End of Treatment (Day 5 or Day 7)
85.5 Percentage of participants
86.4 Percentage of participants

PRIMARY outcome

Timeframe: Day 5 or Day 7 [End of treatment]

Population: Intent-to-Treat (ITT) Population (randomized as per treatment allocation): all randomized participants who received at least one dose of study medication. If the post-Baseline assessment of clinical success response was missing then "Clinical Success" is considered as "No" i.e. the participant was treated as "Clinical Failure".

Clinical success is defined as the achievement of cure or improvement in signs and symptoms of odontogenic infections. Cure is defined as the complete resolution of signs and symptoms of infection present at baseline, such that no additional antimicrobial therapy is required. Improvement is defined as the resolution of fever (if present at baseline), \>70% reduction in swelling and pain and improvement in other signs and symptoms such that no additional antimicrobial therapy is required. Visual Analogue Scale (VAS) is used to measure the amount of pain and swelling that a participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no pain and 10 indicates worst possible pain.

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=234 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=237 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Percentage of Participants Achieving Clinical Success (Cure or Improvement) Considering Clinical Judgment of the Investigator at the End of Treatment (Day 5 or Day 7)
83.3 Percentage of participants
85.7 Percentage of participants

SECONDARY outcome

Timeframe: Day 5

Population: ITT-E Population. Only the participants with Day 5 assessments were considered for analysis.

Clinical success is defined as the achievement of cure or improvement in signs and symptoms of odontogenic infections. Cure is defined as the complete resolution of signs and symptoms of infection present at baseline, such that no additional antimicrobial therapy is required. Improvement is defined as the resolution of fever (if present at baseline), \>70% reduction in swelling and pain and improvement in other signs and symptoms such that no additional antimicrobial therapy is required. Visual Analogue Scale (VAS) is used to measure the amount of pain and swelling that a participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no pain and 10 indicates worst possible pain.

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=220 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=230 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Number of Participants Achieving Clinical Success (Cure or Improvement) Considering Clinical Judgment of the Investigator at Day 5
169 Participants
159 Participants

SECONDARY outcome

Timeframe: Day 5

Population: ITT-E Population

CS is defined as cure or imp in s/sx of odontogenic infections. Cure is defined as the complete resolution of s/sx of infection present at Baseline (BL) and imp is defined as resolution of fever (if present at BL), \>70% reduction in swelling and pain and imp in other s/sx such that no additional antimicrobial (ant) therapy is required. In event of cure or imp with complete resolution of fever and \>70% reduction in swelling and pain, but 'no change' or 'worsening from BL' in other s/sx (like increased leucocyte count/tooth mobility), the inv's opinion was sought on whether additional ant therapy was required. Par. that required no additional ant therapy were considered a 'success' while those requiring additional ant therapy were deemed a 'failure'. For a sensitivity analysis, all such par. with 'no change' or 'worsening from BL' in these other s/sx were considered as cl failures and termed 'Without Considering Cl Jdg of Inv', even though main s/sx are 'cured' or 'improved'. .

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=220 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=230 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Number of Participants (Par.) Achieving Clinical Success (CS) (Cure or Improvement [Imp] in Signs [s] and Symptoms [sx] [s/sx]) Without Considering Clinical (cl) Judgment (Jdg) of the Investigator (Inv) at Day 5
158 Participants
150 Participants

SECONDARY outcome

Timeframe: Baseline, Days 2, 5 and 7

Population: ITT-E Population. Only those participants available indicated time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E population.

Visual Analogue Scale (VAS) is used to measure the amount of pain that the participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no pain and 10 indicates worst possible pain. Change in Pain/Swelling is calculated as VAS score at Baseline minus the score at a later time point (Day 2, 5 or 7).

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=228 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=235 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Change From Baseline in the Visual Analogue Scale Assessment of Pain Score at Days 2, 5 and 7
Day 5, n=219, 228
5.49 Scores on a scale
Interval 5.27 to 5.71
5.38 Scores on a scale
Interval 5.16 to 5.6
Change From Baseline in the Visual Analogue Scale Assessment of Pain Score at Days 2, 5 and 7
Day 7, n=57, 71
6.38 Scores on a scale
Interval 6.02 to 6.74
6.34 Scores on a scale
Interval 6.02 to 6.66
Change From Baseline in the Visual Analogue Scale Assessment of Pain Score at Days 2, 5 and 7
Day 2, n=227, 233
3.34 Scores on a scale
Interval 3.08 to 3.61
3.07 Scores on a scale
Interval 2.81 to 3.33

SECONDARY outcome

Timeframe: Baseline, Days 2, 5 and 7

Population: ITT-E Population. Only those participants available indicated time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E population.

Visual Analogue Scale (VAS) is used to measure the amount of swelling that the participant experiences. This scale has numerical ratings from 0 to 10. Zero indicates no swelling and 10 indicates worst possible swelling. Change in Pain/Swelling is calculated as VAS score at Baseline minus the score at a later time point (Day 2, 5 or 7).

Outcome measures

Outcome measures
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=228 Participants
Participants received amoxicillin 875 mg plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=235 Participants
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Change From Baseline in Visual Analogue Scale Assessment of Swelling at Days 2, 5 and 7
Day 2, n=219, 225
1.92 Scores on a scale
Interval 1.72 to 2.11
1.61 Scores on a scale
Interval 1.42 to 1.8
Change From Baseline in Visual Analogue Scale Assessment of Swelling at Days 2, 5 and 7
Day 5, n=214, 223
3.68 Scores on a scale
Interval 3.51 to 3.85
3.60 Scores on a scale
Interval 3.43 to 3.76
Change From Baseline in Visual Analogue Scale Assessment of Swelling at Days 2, 5 and 7
Day 7, n=55, 68
4.21 Scores on a scale
Interval 3.94 to 4.49
4.61 Scores on a scale
Interval 4.36 to 4.86

Adverse Events

Amoxicillin 875 mg + Clavulanic Acid 125 mg

Serious events: 0 serious events
Other events: 99 other events
Deaths: 0 deaths

Clindamycin 150 mg

Serious events: 0 serious events
Other events: 93 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Amoxicillin 875 mg + Clavulanic Acid 125 mg
n=236 participants at risk
Participants received amoxicillin 875 milligrams (mg) plus clavulanic acid 125 mg orally twice daily with meals for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Clindamycin 150 mg
n=235 participants at risk
Participants received clindamycin 150 mg orally four times daily for a duration of five to seven days in participants with acute odontogenic infection with or without abscess.
Gastrointestinal disorders
Abdominal discomfort
4.7%
11/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
3.0%
7/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Gastrointestinal disorders
Diarrhoea
8.1%
19/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
11.9%
28/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Investigations
Alanine aminotransferase increased
11.0%
26/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
10.2%
24/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Investigations
Aspartate aminotransferase decreased
3.4%
8/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
0.85%
2/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Investigations
Aspartate aminotransferase increased
10.2%
24/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
8.5%
20/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Investigations
Blood bilirubin increased
5.1%
12/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
5.5%
13/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Metabolism and nutrition disorders
Increased appetite
8.5%
20/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
6.4%
15/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Nervous system disorders
Dizziness
7.6%
18/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
6.0%
14/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Nervous system disorders
Headache
3.4%
8/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
6.0%
14/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
Nervous system disorders
Somnolence
8.1%
19/236 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
7.2%
17/235 • Serious adverse events (SAEs) and non-serious AEs were collected from the Baseline (Day 0) until the last dose of study drug (Day 7) or early withdrawal (average of Day 5.88).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

  • Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER