Placebo-Controlled Trial of Antibiotic Therapy in Adults... | NCT03341273

ID	Type	Description	Link
HHSN272201300015I

Status Module

Description Module

Detailed Description

This is a randomized, double-blinded, placebo-controlled, non-inferiority multicenter clinical trial of azithromycin vs. placebo in adults presenting as outpatients with suspect Lower Respiratory Tract Infection (LRTI) and a Procalcitonin (PCT) level of < / = 0.25 ng/mL, as a strategy for reducing antibiotic prescriptions. The study is designed to compare the efficacy of azithromycin versus placebo on Day 5 (i.e., after 4 days of treatment) in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach. The study will recruit potential subjects 18 years of age or older who are suspected to have LRTI. The enrollment cap will be 840 participants, for the goal of approximately 674 randomized participants who will be randomized 1:1 to receive oral azithromycin or placebo for five days. Randomized subjects will have efficacy measured from the time of the first dose of study drug (Day 1) through approximately Day 28. The primary objective is to compare the efficacy of azithromycin versus placebo on Day 5 (i.e., after 4 days of treatment) in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach. The secondary objectives are to compare:1) groups receiving azithromycin versus placebo with regard to all antibiotic use by Days 11 and 28; 2) groups receiving azithromycin versus placebo with regard to return visits to a physician's office or urgent care by Days 11 and 28; 3) groups receiving azithromycin versus placebo with regard to emergency department visits by Days 11 and 28; 4) groups receiving azithromycin versus placebo with regard to hospitalization by Days 11 and 28 if not hospitalized at the enrollment and randomization visit; 5) groups receiving azithromycin versus placebo with regard to improvement in presenting symptoms by Days 11 and 28; 6) the efficacy of azithromycin versus placebo on Day 11 in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach; 7) the efficacy of azithromycin versus placebo on Day 28 in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach; 8) the efficacy of azithromycin versus placebo in subjects with suspected LRTI and PCT levels of < / = 0.25 ng/mL at Day 5 using a superiority approach, employing the "Response Adjusted for Days of Antibiotic Risk (RADAR)" methodology; 9) groups receiving azithromycin versus placebo in regard to solicited events by Day 5; 10) groups receiving azithromycin versus placebo in regard to hospitalization or visits to an Emergency Department (ED), outpatient clinic, or urgent care center for worsening or persistent LRTI after randomization by Day 5; 11) groups receiving azithromycin versus placebo in regard to improvement in vital sign abnormalities or symptoms present at enrollment, on Day 5; 12) groups receiving azithromycin versus placebo in regard to new vital sign abnormalities or symptoms on Day 5, or deterioration in symptoms relative to the enrollment visit on Day 5.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Azithromycin	Experimental	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). N=337	Drug: Azithromycin Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)
Placebo	Placebo Comparator	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). N=337	Other: Placebo Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Azithromycin	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Clinical Improvement at Day 5 Visit (D5V)	Clinical improvement at Day 5 Visit is defined as fulfilling all of the following criteria: Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment Absence of fever in the day preceding or at the D5V 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	Day 5 Visit

Secondary Outcomes

Measure	Description	Time Frame
Clinical Improvement at Day 11 Visit (D11V)	Clinical improvement at Day 11 Visit is defined as fulfilling all of the following criteria: Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment Absence of fever in the day preceding or at the D11V 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Clinician suspected Lower Respiratory Tract Infection (LRTI)* based on the presence of at least two qualifying symptoms** OR one qualifying symptom and at least one qualifying vital sign***.

*LRTI will include acute bronchitis, tracheitis, tracheobronchitis, asthma exacerbation, and acute exacerbation of Chronic obstructive pulmonary disease (COPD) but does not include known pneumonia.

**New cough, worsening of chronic cough, new sputum production, increased volume or purulence of chronic sputum production, chest pain, and difficulty breathing.

***Fever (Provider or patient-measured temperature > / = 37.8 degrees Celsius (100.0 degrees Fahrenheit) or patient-reported feverishness), tachycardia of > / = 90 beats/minute, tachypnea of > 20 breaths/minute.
Males and females age > / = 18 years old.
Presentation > / = 24 hours and < / = 28 days after the onset of at least one qualifying symptom related to the acute episode of illness.
Ability to understand study procedures and willing and able to comply with all required procedures and visits for the entire length of study.
Provide written informed consent before initiation of any study procedures.

Exclusion Criteria:

Hospitalized prior to screening and enrollment. Subjects enrolled in clinic or Emergency Department (ED) setting and then hospitalized during the same clinical encounter may be included.
Chronic pulmonary conditions at the investigator's discretion*.

*Such as:
- Noninvasive ventilation use for any indication other than obstructive sleep apnea
- Long-term invasive mechanical ventilation for any indication
- Known diagnosis of cystic fibrosis or chronic bronchiectasis.
Receipt of an investigational product within 30 days prior to Day 1 or plans to potentially start any investigational product within 30 days after the subject's anticipated study completion.
Current enrollment in another clinical trial of an investigational agent.
Known or suspected infection at any other anatomic site requiring antibacterial therapy.
Immunosuppression*

*Includes:
- Human Immunodeficiency Virus (HIV) infection with CD4 < 200 based on last known measurement or patient-reported value
- History of hematologic malignancies
- Receipt of chemotherapy within the previous 6 months or anticipated receipt of chemotherapy during the study period (1 month)
- Known to have an absolute neutrophil count of < 500 cells/mL or an expectation of an absolute neutrophil count of < 500 cells/mL during course of the study
- Current systemic corticosteroid use (equivalent of 20mg prednisone per day for > / = 2 weeks within the last month)
- Systemic non-steroid immunosuppressive or biologic therapy for transplant, rheumatologic conditions, or other conditions within the last month. Biologics used specifically for control of moderate to severe asthma, including anti-IgE monoclonal antibody therapy (Xolair) or IL-5 monoclonal antibodies (Mepolizumab and Reslizumab) are allowed
Contraindication to the use of azithromycin including history of allergy or intolerance to azithromycin or known prolonged QTc interval (> 500 msec).
Any condition that in the judgment of the referring provider or site investigator precludes participation because it could affect subject safety or ability of subject to participate in this trial.
Prior use of azithromycin in the past two weeks.
Use of any systemic antibiotic in the previous 24 hours.
Previous randomization in this trial.

Facility	Status	City	State	ZIP	Country	Contacts
The Hope Clinic of Emory University		Atlanta	Georgia	30332	United States
Atlanta VA Medical Center - Infectious Diseases Clinic

PubMed Identifier	Type	Citation	Retractions
36525985	Derived	Tsalik EL, Rouphael NG, Sadikot RT, Rodriguez-Barradas MC, McClain MT, Wilkins DM, Woods CW, Swamy GK, Walter EB, El Sahly HM, Keitel WA, Mulligan MJ, Tuyishimire B, Serti E, Hamasaki T, Evans SR, Ghazaryan V, Lee MS, Lautenbach E; TRAP-LRTI Study Group; Antibacterial Resistance Leadership Group. Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial. Lancet Infect Dis. 2023 Apr;23(4):484-495. doi: 10.1016/S1473-3099(22)00735-6. Epub 2022 Dec 13.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 28, 2020	Jul 29, 2021

ID	Title	Description
BG000	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).
BG001	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).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000249 BG001250 BG002499

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Clinical Improvement at Day 5 Visit (D5V)

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

Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment
Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment
Absence of fever in the day preceding or at the D5V
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

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

Posted

Number

95% Confidence Interval

percentage of participants

Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts
Participants	OG000249 OG001250

Title

Denominators

Categories

Title	Measurements
	OG00069(61 to 77) OG00163(54 to 71)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null Hypothesis: Proportion in placebo - Proportion in azithromycin = -12.5%				The null hypothesis was evaluated using a non-inferiority test and non-inferiority of placebo was concluded if the lower limit of the 95% confidence interval for the difference in proportions of clinical improvement was greater than -12.5%.	Risk Difference (RD)	-6			2-Sided	95	-15	2			Multiple imputation with a linear model to impute missing clinical values of improvement. The study day that D5V occurred on was included as a covariate in the final model and the estimates for risk difference assume that study day of D5V is 5.

Secondary

Clinical Improvement at Day 11 Visit (D11V)

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

Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment
Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment
Absence of fever in the day preceding or at the D11V
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.

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

Posted

Number

95% Confidence Interval

percentage of participants

Day 11 Visit

ID	Title	Description
OG000	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).
OG001	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).

Secondary

Clinical Improvement at Day 28 Visit (D28V)

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

Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment
Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment
Absence of fever in the day preceding or at the D11V
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.

Posted

Number

95% Confidence Interval

percentage of participants

Day 28 Visit

ID	Title	Description
OG000	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).
OG001	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).

Secondary

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

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.

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

Posted

Count of Participants

Participants

Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Secondary

Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 11 Visit

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.

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.

Posted

Count of Participants

Participants

Day 11 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts

Secondary

Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 28 Visit

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.

Posted

Count of Participants

Participants

Day 28 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts

Secondary

Number of Participants Exhibiting Improvement in at Least Two Presenting Signs or Symptoms at Day 5 Visit

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.

Posted

Count of Participants

Participants

Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Secondary

Number of Participants Exhibiting Worsening or Deterioration in One or More Symptoms at Day 5 Visit

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.

Posted

Count of Participants

Participants

Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts
Participants

Secondary

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

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.

Posted

Count of Participants

Participants

Day 1 through Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Secondary

Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit

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.

Posted

Count of Participants

Participants

Day 1 through Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts
Participants

Secondary

Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit

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.

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.

Posted

Count of Participants

Participants

Day 1 through Day 11

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts

Secondary

Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit

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.

Posted

Count of Participants

Participants

Day 1 through Day 28 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts

Secondary

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

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.

Posted

Count of Participants

Participants

Day 1 through Day 11 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts

Secondary

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

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.

Posted

Count of Participants

Participants

Day 1 through Day 28 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts

Secondary

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

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.

Posted

Count of Participants

Participants

Day 1 through Day 11 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units

Secondary

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

Posted

Count of Participants

Participants

Day 1 through Day 28 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units

Secondary

Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit

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

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.

Posted

Count of Participants

Participants

Day 5 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units

Secondary

Quantification of All Antibiotic Use From Day 1 Through Day 11 Visit

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.

Posted

Mean

95% Confidence Interval

days

Day 1 through Day 11 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts
Participants

Secondary

Quantification of All Antibiotic Use From Day 1 Through Day 28 Visit

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.

Posted

Mean

95% Confidence Interval

days

Day 1 through Day 28 Visit

ID	Title	Description
OG000	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).
OG001	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).

Units	Counts
Participants

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).	0	242	0	0	114	242
EG001	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).	0	247	0	0	97	247

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG000160 events61 affected242 at risk EG001119 events43 affected247 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG000232 events73 affected242 at risk EG001229 events65 affected247 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00030 events16 affected242 at risk EG00133 events16 affected247 at risk
Candida Infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG00059 events14 affected242 at risk EG0010 events0 affected247 at risk

ID	Term
D004917	Erythromycin
D018942	Macrolides
D061065	Polyketides
D007783	Lactones
D009930	Organic Chemicals