Trial Outcomes & Findings for Treatment of Acute Sinusitis With High-Dose vs. Standard-Dose Amoxicillin/Clavulanate (NCT NCT03431337)

NCT ID: NCT03431337

Last Updated: 2021-08-12

Results Overview

Rating on a scale of 1=a lot worse, 2=a little worse, 3=the same, 4=a little better, 5=a lot better, 6=no symptoms, with a higher score indicating greater improvement.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 157 participants
• Primary outcome timeframe: At end of 3 days of treatment
• Results posted on: 2021-08-12

Participant Flow

Participant milestones

Measure	High Dose Amoxicillin/clavulanate 875mg/125mg \& amoxicillin 875 mg twice a day x 7 days Amoxicillin 875 mg: Doubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125	Standard Dose Amoxicillin/clavulanate 875 mg/125mg \& placebo (lactase) twice a day x 7 days. Placebo (lactase): Placebo (in place of additional amoxicillin in experimental arm)
Overall Study STARTED	78	79
Overall Study COMPLETED	49	57
Overall Study NOT COMPLETED	29	22

Reasons for withdrawal

Measure	High Dose Amoxicillin/clavulanate 875mg/125mg \& amoxicillin 875 mg twice a day x 7 days Amoxicillin 875 mg: Doubling the dose of amoxicillin by adding amoxicillin 875 to each dose of the standard treatment of amoxicillin/clavulanate 875/125	Standard Dose Amoxicillin/clavulanate 875 mg/125mg \& placebo (lactase) twice a day x 7 days. Placebo (lactase): Placebo (in place of additional amoxicillin in experimental arm)
Overall Study Lost to Follow-up	21	19
Overall Study Withdrawal by Subject	8	3

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	High Dose n=78 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=79 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo	Total n=157 Participants Total of all reporting groups
Age, Continuous	48.5 years STANDARD_DEVIATION 15.8 • n=78 Participants	48.5 years STANDARD_DEVIATION 16.2 • n=79 Participants	48.5 years STANDARD_DEVIATION 16.0 • n=157 Participants
Sex: Female, Male Female	57 Participants n=78 Participants	60 Participants n=79 Participants	117 Participants n=157 Participants
Sex: Female, Male Male	21 Participants n=78 Participants	19 Participants n=79 Participants	40 Participants n=157 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Smoking (No. [%]	12 Participants n=78 Participants	7 Participants n=79 Participants	19 Participants n=157 Participants
Asthma or COPD	13 Participants n=78 Participants	7 Participants n=79 Participants	20 Participants n=157 Participants
Diabetes	4 Participants n=78 Participants	6 Participants n=79 Participants	10 Participants n=157 Participants
Allergic rhinitis	10 Participants n=78 Participants	21 Participants n=79 Participants	31 Participants n=157 Participants
Heart disease	3 Participants n=78 Participants	3 Participants n=79 Participants	6 Participants n=157 Participants
History of sinusitis	19 Participants n=78 Participants	22 Participants n=79 Participants	41 Participants n=157 Participants
Hospitalized in past month	0 Participants n=78 Participants	0 Participants n=79 Participants	0 Participants n=157 Participants
Antibiotics in past month	1 Participants n=78 Participants	3 Participants n=79 Participants	4 Participants n=157 Participants
Using nasal steroids	18 Participants n=78 Participants	19 Participants n=79 Participants	37 Participants n=157 Participants
Enrolled in previous study	10 Participants n=78 Participants	7 Participants n=79 Participants	17 Participants n=157 Participants
Days of illness prior to enrollment	13.9 days STANDARD_DEVIATION 6.0 • n=78 Participants	17.1 days STANDARD_DEVIATION 11.0 • n=79 Participants	15.4 days STANDARD_DEVIATION 8.9 • n=157 Participants
Sinusitis category 1 (duration 10 days or greater)	54 Participants n=78 Participants	58 Participants n=79 Participants	112 Participants n=157 Participants
Sinusitis category 2 (severe symptoms)	5 Participants n=78 Participants	6 Participants n=79 Participants	11 Participants n=157 Participants
Sinusitis category 3 (double sickening)	18 Participants n=78 Participants	12 Participants n=79 Participants	30 Participants n=157 Participants
Sinonasal Outcome Test-16 total score	29.4 units on a scale STANDARD_DEVIATION 7.4 • n=78 Participants	29.4 units on a scale STANDARD_DEVIATION 8.0 • n=79 Participants	29.4 units on a scale STANDARD_DEVIATION 7.7 • n=157 Participants
Tend to be constipated	15 Participants n=78 Participants	19 Participants n=79 Participants	34 Participants n=157 Participants
Prone to diarrhea	11 Participants n=78 Participants	16 Participants n=79 Participants	27 Participants n=157 Participants
Tend to get vaginal yeast infections	15 Participants n=78 Participants	15 Participants n=79 Participants	30 Participants n=157 Participants

PRIMARY outcome

Timeframe: At end of 3 days of treatment

Population: Participants who provided a Global Rating of Improvement when contacted at the end of 3 days of treatment.

Rating on a scale of 1=a lot worse, 2=a little worse, 3=the same, 4=a little better, 5=a lot better, 6=no symptoms, with a higher score indicating greater improvement.

Outcome measures

Measure	High Dose n=66 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=70 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants With a Global Rating of Improvement of 5 & 6 at the End of 3 Days of Treatment	24 Participants	31 Participants

SECONDARY outcome

Timeframe: At end of 10 days since enrollment

Population: Participants who could be reached to give a global rating at the end of 10 days since enrollment.

Rating of 5 (a lot better) or 6 (no symptoms) on Global Rating of Improvement scale, with range of 1 (a lot worse) to 6 (no symptoms), with a higher score indicating greater improvement

Outcome measures

Measure	High Dose n=49 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=57 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants With a Global Rating of Improvement of 5 or 6 at End of 10 Days Since Enrollment	35 Participants	47 Participants

SECONDARY outcome

Timeframe: At end of 3 days of treatment

Population: Participants who provided a SNOT-16 rating when reached at the end of 3 days

The change between enrollment and the end of 3 days of treatment in the total score on the Sinonasal Outcome Test-16 (SNOT-16). The total SNOT-16 is the sum of the participant's ratings of 16 symptoms of illness on the scale of 0 (no problem) to 3 (severe problem), with a possible range of 0 to 48, with a higher sum indicating more troubling symptoms. A decrease in total score would indicate an improvement in symptoms.

Outcome measures

Measure	High Dose n=65 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=71 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 3 Days of Treatment	13.3 score on a scale Standard Deviation 8.8	12.3 score on a scale Standard Deviation 11.5

SECONDARY outcome

Timeframe: At end of 10 days since enrollment

Population: Participants who could be reached at 10 days since enrollment

The change between enrollment and the end of 10 days since enrollment in the total score on the Sinonasal Outcome Test-16 (SNOT-16). The total SNOT-16 is the sum of the participant's ratings of 16 symptoms of illness on the scale of 0 (no problem) to 3 (severe problem), with a possible range of 0 to 48, with a higher sum indicating more troubling symptoms. A decrease in total score would indicate an improvement in symptoms.

Outcome measures

Measure	High Dose n=49 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=56 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Change From Baseline in the Total Score on the Sinonasal Outcome Test-16 (SNOT-16) at the End of 10 Days Since Enrollment	18.4 score on a scale Standard Deviation 11.4	21.4 score on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: At end of 10 days since enrollment

Population: Participants who could be reached to assess their treatment at 10 days since enrollment

Assessment of balance between good effects and bad effects of antibiotic on scale of -3=bad effects much greater than good effects to +3=good effects much greater than bad effects

Outcome measures

Measure	High Dose n=48 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=58 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Balance of Benefits and Detriments	1.8 score on a scale Standard Deviation 1.8	2.2 score on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: At end of 10 days since enrollment

Population: Participants who could be reached at day 10 to assess their treatment

Response of "yes" at the end of 10 days since enrollment to the question whether the participant would take this antibiotic again, with possible answers of yes, no, or uncertain.

Outcome measures

Measure	High Dose n=48 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=58 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants Answering "Yes" to Willingness to Take the Antibiotic Again in the Future	34 Participants	47 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At the end of 3 days

Population: Participants giving a rating of diarrhea at the end of day 3

Among those who indicated at enrollment whether prone to diarrhea or not, the number giving ratings of 1, 2, or 3 on diarrhea scale ranging from 0 (none) to 3 (severe)

Outcome measures

Measure	High Dose n=26 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=105 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants Reporting Any Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea	16 Participants	41 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At end of day 3

Population: Participants who indicated whether prone to diarrhea or not at enrollment and then at follow-up rated their diarrhea

Among those reporting proneness to diarrhea or not at enrollment, the number rating 3 on diarrhea scale ranging from 0 (none) to 3 (severe)

Outcome measures

Measure	High Dose n=26 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=105 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants Reporting Severe Diarrhea at Day 3 Among Those Self-identified as Prone or Not Prone to Diarrhea	4 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At 10 days since enrollment

Population: Participants indicating their adverse effects at 10 days

Among those indicating at enrollment a proneness or not to diarrhea, the number giving ratings of 1, 2, or 3 on the diarrhea scale ranging from 0 (none) to 3 (severe)

Outcome measures

Measure	High Dose n=21 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=105 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants Reporting Any Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea	6 Participants	21 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At 10 days since enrollment

Population: Participants who gave ratings of adverse effects at day 10

Among those indicating proneness to diarrhea or not at enrollment, the number who gave a rating of 3 on the diarrhea scale ranging from 0 (none) to 3 (severe)

Outcome measures

Measure	High Dose n=21 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=80 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Participants Reporting Severe Diarrhea at Day 10 Among Those Self-identified as Prone or Not Prone to Diarrhea	1 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: After 3 days of treatment

Population: Female participants available at the end of 3 days of treatment who had indicated proneness or not to vaginal symptoms at enrollment

Female participants contacted after 3 days of treatment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave ratings of 1, 2, or 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.

Outcome measures

Measure	High Dose n=24 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=72 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Female Participants Reporting Any Vaginal Symptoms at Day 3 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge	6 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At the end of 3 days of treatment

Population: Female participants reporting adverse effects at day 3

Among female participants indicating a proneness or not to vaginal itching or discharge, the number of ratings of 3 on the vaginal symptom scale ranging from 0 (none) to 3 (severe)Female participants contacted after 3 days of treatment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave a rating of 1, 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.

Outcome measures

Measure	High Dose n=24 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=72 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Female Participants Reporting Severe Vaginal Symptoms at Day 3 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge	0 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At 10 days since enrollment

Female participants contacted after 10 days since enrollment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave ratings of 1, 2, or 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.

Outcome measures

Measure	High Dose n=24 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=53 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Female Participants Reporting Any Vaginal Symptoms at Day 10 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge	10 Participants	9 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At 10 days since enrollment

Population: Female participants giving ratings of adverse effects at day 10

Female participants contacted at 10 days since enrollment were divided into two groups: those who had or had not reported at baseline a proneness to vaginal symptoms. The measure was the number in each group who gave rating of 3 on the vaginal symptoms scale, ranging from 0 (none) to 3 (severe), with a higher score indicating more severe symptoms.

Outcome measures

Measure	High Dose n=24 Participants Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=53 Participants Amoxicillin 875 mg/clavulanate 125 mg + placebo
Number of Female Participants Reporting Severe Vaginal Symptoms at Day 10 Among Those Self-identified as Prone or Not Prone to Vaginal Itching or Discharge	0 Participants	1 Participants

Adverse Events

High Dose

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

Standard Dose

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	High Dose n=78 participants at risk Amoxicillin 875 mg/clavulanate 125 mg + amoxicillin 875 mg twice a day x 7 days	Standard Dose n=79 participants at risk Amoxicillin 875 mg/clavulanate 125 mg + placebo
Gastrointestinal disorders Severe diarrhea at day 3	7.7% 5/65 • Number of events 5 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	7.0% 5/71 • Number of events 5 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Gastrointestinal disorders Any diarrhea day 3	43.1% 28/65 • Number of events 28 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	40.8% 29/71 • Number of events 29 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Gastrointestinal disorders Severe diarrhea day 10	6.1% 3/49 • Number of events 3 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	3.4% 2/58 • Number of events 2 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Gastrointestinal disorders Any diarrhea day 10	28.6% 14/49 • Number of events 14 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	24.1% 14/58 • Number of events 14 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Infections and infestations Severe vaginal itching or discharge day 3	4.4% 2/45 • Number of events 2 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	0.00% 0/55 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Infections and infestations Any vaginal itching or discharge day 3	13.3% 6/45 • Number of events 6 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	20.0% 11/55 • Number of events 11 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Infections and infestations Severe vaginal discharge or itching day 10	2.9% 1/35 • Number of events 1 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	0.00% 0/47 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events
Infections and infestations Any vaginal itching or discharge day 10	25.7% 9/35 • Number of events 9 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events	21.3% 10/47 • Number of events 10 • 10 days since enrollment Participants were asked about adverse events at the end of 3 and 10 days. Since they were are office patients, we would have been aware of deaths or serious adverse events

Additional Information

Dr. Paul Sorum

Albany Medical College

Phone: 518-262-7500

Email: sorump@amc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place