Trial Outcomes & Findings for Placebo-Controlled Trial of Antibiotic Therapy in Adults With Suspect Lower Respiratory Tract Infection (LRTI) and a Procalcitonin Level (NCT NCT03341273)

NCT ID: NCT03341273

Last Updated: 2023-06-28

Results Overview

Clinical improvement at Day 5 Visit is defined as fulfilling all of the following criteria: 1. Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment 2. Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment 3. Absence of fever in the day preceding or at the D5V 4. No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening Lower Respiratory Tract Infection (LRTI) at any time after randomization

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 514 participants
• Primary outcome timeframe: Day 5 Visit
• Results posted on: 2023-06-28

Participant Flow

Adult participants, males and non-pregnant females, aged >=18 years, presenting as outpatients with suspected Lower Respiratory Tract Infection (LRTI) with a Procalcitonin (PCT) level of <=0.25 ng/mL were recruited from the community at large. Participants were enrolled between 08DEC2017 and 09MAR2020.

Participant milestones

Measure	Azithromycin 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5). Azithromycin: Azithromycin is an azalide antibiotic and is derived from erythromycin used to treat many different types of infections caused by bacteria, such as respiratory infections. VIDAS B.R.A.H.M.S Procalcitonin Test (PCT): The VIDAS B.R.A.H.M.S PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma using the Enzyme-Linked Fluorescent Assay (ELFA) technique.	Placebo 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5). Placebo: Placebo will be a matching capsule the same size, weight, and color as the capsules containing Azithromycin tablets. VIDAS B.R.A.H.M.S Procalcitonin Test (PCT): The VIDAS B.R.A.H.M.S PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma using the Enzyme-Linked Fluorescent Assay (ELFA) technique.
Overall Study STARTED	249	250
Overall Study COMPLETED	229	238
Overall Study NOT COMPLETED	20	12

Reasons for withdrawal

Measure	Azithromycin 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5). Azithromycin: Azithromycin is an azalide antibiotic and is derived from erythromycin used to treat many different types of infections caused by bacteria, such as respiratory infections. VIDAS B.R.A.H.M.S Procalcitonin Test (PCT): The VIDAS B.R.A.H.M.S PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma using the Enzyme-Linked Fluorescent Assay (ELFA) technique.	Placebo 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5). Placebo: Placebo will be a matching capsule the same size, weight, and color as the capsules containing Azithromycin tablets. VIDAS B.R.A.H.M.S Procalcitonin Test (PCT): The VIDAS B.R.A.H.M.S PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma using the Enzyme-Linked Fluorescent Assay (ELFA) technique.
Overall Study Lost to Follow-up	7	7
Overall Study Withdrawal by Subject	4	2
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	0	1
Overall Study Enrolled but Treatment Not Administered	6	1
Overall Study Became ineligible after enrollment	1	0
Overall Study Not Eligible at Enrollment	0	1
Overall Study Participant incarcerated	1	0

Baseline Characteristics

Placebo-Controlled Trial of Antibiotic Therapy in Adults With Suspect Lower Respiratory Tract Infection (LRTI) and a Procalcitonin Level

Baseline characteristics by cohort

Measure	Azithromycin n=249 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=250 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).	Total n=499 Participants Total of all reporting groups
Age, Continuous	52.8 years STANDARD_DEVIATION 15.9 • n=5 Participants	51.7 years STANDARD_DEVIATION 15.0 • n=7 Participants	52.2 years STANDARD_DEVIATION 15.5 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	96 Participants n=7 Participants	176 Participants n=5 Participants
Sex: Female, Male Male	169 Participants n=5 Participants	154 Participants n=7 Participants	323 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	228 Participants n=5 Participants	233 Participants n=7 Participants	461 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	159 Participants n=5 Participants	146 Participants n=7 Participants	305 Participants n=5 Participants
Race (NIH/OMB) White	81 Participants n=5 Participants	89 Participants n=7 Participants	170 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	249 participants n=5 Participants	250 participants n=7 Participants	499 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 5 Visit

Population: The ITT population includes all participants with PCT \<= 0.25 ng/mL who were randomized to receive study product.

Clinical improvement at Day 5 Visit is defined as fulfilling all of the following criteria:

1. Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment

2. Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment

3. Absence of fever in the day preceding or at the D5V

4. No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening Lower Respiratory Tract Infection (LRTI) at any time after randomization

Outcome measures

Measure	Azithromycin n=249 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=250 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Clinical Improvement at Day 5 Visit (D5V)	69 percentage of participants Interval 61.0 to 77.0	63 percentage of participants Interval 54.0 to 71.0

SECONDARY outcome

Timeframe: Day 11 Visit

Population: The ITT population includes all participants with PCT \<= 0.25 ng/mL who were randomized to receive study product.

Clinical improvement at Day 11 Visit is defined as fulfilling all of the following criteria:

1. Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment

2. Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment

3. Absence of fever in the day preceding or at the D11V

4. No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening LRTI at any time after randomization The ITT population includes all participants with PCT = 0.25 ng/mL who were randomized to receive study product.

Outcome measures

Measure	Azithromycin n=249 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=250 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Clinical Improvement at Day 11 Visit (D11V)	81 percentage of participants Interval 74.0 to 87.0	76 percentage of participants Interval 70.0 to 83.0

SECONDARY outcome

Timeframe: Day 28 Visit

Population: The ITT population includes all participants with PCT \<= 0.25 ng/mL who were randomized to receive study product.

Clinical improvement at Day 28 Visit is defined as fulfilling all of the following criteria:

1. Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment

2. Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment

3. Absence of fever in the day preceding or at the D11V

4. No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening LRTI at any time after randomization

Outcome measures

Measure	Azithromycin n=249 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=250 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Clinical Improvement at Day 28 Visit (D28V)	88 percentage of participants Interval 83.0 to 93.0	82 percentage of participants Interval 77.0 to 86.0

SECONDARY outcome

Timeframe: Day 5 Visit

Population: The ITT population includes all participants with PCT\<= 0.25 ng/mL who were randomized to receive study product.

DOOR is a composite endpoint created using clinical outcomes from Day 1 through Day 5 Visit. It is based on adequate clinical improvement at Day 5 Visit and solicited events from Day 1 through Day 5 Visit.

When comparing two participants with different ordinal clinical outcomes (OCOs), the participant with a better OCO receives a higher DOOR rank. When comparing two participants with the same OCOs, the participant with fewer days of antibiotic use receives a higher DOOR rank.

Outcome measures

Measure	Azithromycin n=249 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=250 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit Adequate clinical improvement (ACI) with no adverse events	82 Participants	94 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit Adequate clinical improvement with mild adverse events	47 Participants	33 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit Adequate clinical improvement with moderate adverse events	25 Participants	18 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit Adequate clinical improvement with severe adverse events	1 Participants	3 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit No adequate clinical improvement with no medically attended events	62 Participants	72 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit No ACI with ED, outpatient clinic, or urgent care center visit but no hospitalization	9 Participants	15 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit No adequate clinical improvement with hospitalization	1 Participants	3 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit 8: Death (any cause)	0 Participants	0 Participants
Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit Missing	22 Participants	12 Participants

SECONDARY outcome

Timeframe: Day 11 Visit

Population: According-to-protocol at Day 11 (ATP-11) Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D11V within the protocol defined time window, and had sufficient data to define clinical improvement at D11V.

Improvement in LRTI symptoms was defined as presence of at least one-step improvement in the symptom present at baseline. For fever, improvement was defined as changing from presence of fever at baseline to absence of fever at Day 11 Visit.

Outcome measures

Measure	Azithromycin n=211 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=225 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 11 Visit	206 Participants	221 Participants

SECONDARY outcome

Timeframe: Day 28 Visit

Population: ATP-28 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D28V within the protocol defined time window, and had sufficient data to define clinical improvement at D28V.

Improvement in LRTI symptoms was defined as presence of at least one-step improvement in the symptom present at baseline. For fever, improvement was defined as changing from presence of fever at baseline to absence of fever at Day 28 Visit.

Outcome measures

Measure	Azithromycin n=210 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=223 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 28 Visit	207 Participants	220 Participants

SECONDARY outcome

Timeframe: Day 5 Visit

Population: ATP-5 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D5V in person within the protocol defined time window, and had sufficient data to define clinical improvement at D5V.

Improvement in LRTI symptoms was defined as presence of at least one-step improvement in at least two symptoms present at baseline for participants who qualified based on two symptoms or improvement in one LRTI symptom present at baseline and normalization of one abnormal vital sign at Day 5 Visit for participants who qualified based on one symptom and one vital sign abnormality.

Outcome measures

Measure	Azithromycin n=204 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=221 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants Exhibiting Improvement in at Least Two Presenting Signs or Symptoms at Day 5 Visit	166 Participants	177 Participants

SECONDARY outcome

Timeframe: Day 5 Visit

Population: ATP-5 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D5V in person within the protocol defined time window, and had sufficient data to define clinical improvement at D5V.

Clinical deterioration at D5V is defined as at least one-step deterioration (worsening from mild to moderate for example) in any qualifying symptoms or presence of a new vital abnormality at D5V not present at enrollment.

Outcome measures

Measure	Azithromycin n=204 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=221 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants Exhibiting Worsening or Deterioration in One or More Symptoms at Day 5 Visit	29 Participants	32 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 5 Visit

Population: ATP-5 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D5V in person within the protocol defined time window, and had sufficient data to define clinical improvement at D5V.

This table summarizes the number and percentage of participants reporting any medically attended visits any time after randomization. Note that receipt of a non-study antibiotic after study Day 5 Visit will was not regarded as satisfying this definition if it is related to a new non-respiratory process that is unrelated to the prior diagnosis of LRTI.

Outcome measures

Measure	Azithromycin n=204 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=221 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants Reporting One or More Hospitalization or Visits to an Emergency Department (ED), Outpatient Clinic, or Urgent Care Center (After Randomization) for Worsening or Persistent Lower Respiratory Tract Infection	9 Participants	15 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 5 Visit

Population: ATP-5 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D5V in person within the protocol defined time window, and had sufficient data to define clinical improvement at D5V.

This table summarizes the number and percentage of participants experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 5 Visit.

Outcome measures

Measure	Azithromycin n=204 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=221 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit Any Event	90 Participants	77 Participants
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit Abdominal Pain	47 Participants	35 Participants
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit Vomiting	13 Participants	10 Participants
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit Diarrhea	53 Participants	55 Participants
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit Allergic Reaction	8 Participants	9 Participants
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit Candidiasis	8 Participants	8 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 11

Population: ATP-11 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D11V within the protocol defined time window, and had sufficient data to define clinical improvement at D11V.

This table summarizes the number of participants with one or more Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 11 Visit.

Outcome measures

Measure	Azithromycin n=221 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=225 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit	3 Participants	9 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 28 Visit

Population: ATP-28 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D28V within the protocol defined time window, and had sufficient data to define clinical improvement at D28V.

This table summarizes the number of participants with one or more Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) in Azithromycin Group from Day 1 through Day 28 Visit.

Outcome measures

Measure	Azithromycin n=210 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=223 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit	3 Participants	9 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 11 Visit

Population: ATP-11 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D11V within the protocol defined time window, and had sufficient data to define clinical improvement at D11V.

This table summarizes the number of participants with one or more hospitalizations for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 11 Visit.

Outcome measures

Measure	Azithromycin n=211 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=225 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With One or More Hospitalizations (if Not Hospitalized at Enrollment) for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 28 Visit

Population: ATP-28 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D28V within the protocol defined time window, and had sufficient data to define clinical improvement at D28V.

This table summarizes the number of participants with one or more hospitalizations for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 28 Visit.

Outcome measures

Measure	Azithromycin n=210 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=223 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With One or More Hospitalizations (if Not Hospitalized at Enrollment) for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 11 Visit

Population: ATP-11 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D11V within the protocol defined time window, and had sufficient data to define clinical improvement at D11V.

This table summarizes the number of participants with one or more unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 11 Visit.

Outcome measures

Measure	Azithromycin n=211 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=225 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With One or More Unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit	5 Participants	7 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 28 Visit

Population: ATP-28 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D28V within the protocol defined time window, and had sufficient data to define clinical improvement at D28V.

This table summarizes the number of participants with one or more unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 28 Visit.

Outcome measures

Measure	Azithromycin n=210 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=223 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With One or More Unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit	6 Participants	7 Participants

SECONDARY outcome

Timeframe: Day 5 Visit

Population: ATP-5 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D5V in person within the protocol defined time window, and had sufficient data to define clinical improvement at D5V. For vital signs, only participants with without the vital sign abnormality are analyzed. For fever, only participants with non-missing values for fever are analyzed.

This table summarizes the number and percentage of participants experiencing new vital signs abnormalities at Day 5 Visit that were not present at baseline.

Outcome measures

Measure	Azithromycin n=202 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=216 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit Any Vital Sign	19 Participants	24 Participants
Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit Temperature	0 Participants	0 Participants
Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit Pulse	17 Participants	19 Participants
Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit Respiratory Rate	3 Participants	5 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 11 Visit

Population: ATP-11 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D11V within the protocol defined time window, and had sufficient data to define clinical improvement at D11V.

The table summarizes the mean number of days of antibiotic use including study and non-study antibiotics for participants from Day 1 through Day 11 Visit.

Outcome measures

Measure	Azithromycin n=211 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=225 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Quantification of All Antibiotic Use From Day 1 Through Day 11 Visit	5.1 days Interval 5.0 to 5.3	0.3 days Interval 0.1 to 0.5

SECONDARY outcome

Timeframe: Day 1 through Day 28 Visit

Population: ATP-28 Population includes randomized participants who had no major protocol deviations and consumed 5 doses of study product by D5V, completed their D28V within the protocol defined time window, and had sufficient data to define clinical improvement at D28V.

The table summarizes the mean number of days of antibiotic use including study and non-study antibiotics for participants from Day 1 through Day 28 Visit.

Outcome measures

Measure	Azithromycin n=210 Participants 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=223 Participants 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Quantification of All Antibiotic Use From Day 1 Through Day 28 Visit	5.5 days Interval 5.2 to 5.9	0.9 days Interval 0.5 to 1.4

Adverse Events

Azithromycin

Serious events: 0 serious events

Other events: 114 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Azithromycin n=242 participants at risk 500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5).	Placebo n=247 participants at risk 2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5).
Gastrointestinal disorders Abdominal Pain	25.2% 61/242 • Number of events 160 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.	17.4% 43/247 • Number of events 119 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.
Gastrointestinal disorders Diarrhoea	30.2% 73/242 • Number of events 232 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.	26.3% 65/247 • Number of events 229 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.
Gastrointestinal disorders Vomiting	6.6% 16/242 • Number of events 30 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.	6.5% 16/247 • Number of events 33 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.
Infections and infestations Candida Infection	5.8% 14/242 • Number of events 59 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.	0.00% 0/247 • Solicited Adverse Events were collected from Day 1 through Day 11. As the safety profile of azithromycin is well established, and this trial was not powered to detect new, unknown safety signals, there was no azithromycin-related Adverse Event (AE) collection or Serious Adverse Events (SAEs) reporting during this study. Unanticipated adverse device effect (UADE) were unexpected, but were to be reported appropriately if they occurred during the study. Serious adverse events were not collected for this study, therefore the number of participants at risk for serious adverse events is zero.

Additional Information

Ephraim L. Tsalik, MD, MHS, PhD

Duke University

Phone: 919-684-3114

Email: e.t@duke.edu

Results disclosure agreements

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