Pneumonia
Conditions
Keywords
Antimicrobial, Beta-Lactam, Pneumonia, Short Course, Standard Course, Therapy
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled, superiority clinical trial will test the effectiveness of short (5-day) vs.standard (10-day) course therapy in children who are diagnosed with CAP and initially treated in outpatient clinics, urgent care facilities, and emergency departments. Primary objective is to compare the composite overall outcome (Desirability of Outcome Ranking, DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visit #1 (Study Day 8 +/- 2 days)
Detailed description
This is a multi-center, randomized, double-blind, placebo-controlled, superiority clinical trial evaluating short course (5 day) vs. standard course (10 day) of oral beta-lactam antibiotic therapy (amoxicillin, amoxicillin-clavulanate, cefdinir) for treatment of CAP in children 6-71 months of age who have clinically improved prior to enrollment. The study will randomize approximately 400 enrolled subjects to one of the two study arms (approximately 200 children in each arm) in order to reach 360 subjects completing Outcome Assessment Visit 1. Subjects will be randomized (1:1) to receive either a standard course of the initially prescribed antibiotic (10 days) or a short course of the initially prescribed antibiotic (5 days) plus 5 days of matching placebo. The study will recruit potential subjects from children who are diagnosed with CAP and who are initiated on oral beta-lactam therapy by healthcare providers in EDs, outpatient clinics, and urgent care centers at the study sites. Day -5 is defined as the date on which oral beta-lactam therapy is initiated for a diagnosis of CAP. Potential subjects will be identified at any time following clinical diagnosis of pneumonia. These subjects will be assessed for eligibility and enrolled on Day -3 to -1 of their initially prescribed oral beta-lactam therapy. Subjects may also be enrolled on Day 1 (the first day of receipt of study agent) provided they have not yet received any doses of the healthcare provider-prescribed antibiotic therapy for that day. The Primary objective is to compare the composite overall outcome (Desirability of Outcome Ranking, DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visit #1 (Study Day 8 +/- 2 days). The Secondary objectives are: 1) To compare the composite overall outcome (DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visit #2 (Study Day 22 +/- 3 days); 2) To compare the resolution of symptoms (a component of DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visits #1 and #2; 3) To compare the clinical response (a component of DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visits #1 and #2; 4) To compare solicited events (a component of DOOR) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visits #1 and #2; 5) To compare medically attended visits to Emergency Departments (ED) or outpatient clinics, hospitalizations, surgical procedures, and receipt of non-study systemic antibiotics (components of the clinical response) among children 6-71 months of age with CAP assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient beta-lactam therapy at Outcome Assessment Visits #1 and #2
Interventions
DRUGAmoxicillin
Amoxicillin is an aminopenicillin antibiotic
A fixed-ratio combination of amoxicillin trihydrate, an aminopenicillin, and potassium clavulanate, a beta-lactamase inhibitor, used to treat a broad-spectrum of bacterial infections, especially resistant strains.
DRUGCefdinir
Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
OTHERPlacebo
Placebo
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 71 Months
Healthy volunteers
No
Inclusion criteria
1. Age 6 - 71 months 2. Provider diagnosis of CAP and prescription of antibiotic therapy with amoxicillin, amoxicillin-clavulanate, or cefdinir \- amoxicillin or amoxicillin-clavulanate prescribed at a amoxicillin dose of 60 mg/kg/day \-- cefdinir prescribed at a minimum dose of 10 mg/kg/day 3. Parental report of clinical improvement \- based on lack of either subjective or known fever temperature \>/= 38.3°C in the preceding 24 hours; current respiratory rate no greater than 50 breaths/minute (\<2 years of age) or breaths/minute (= / \> 2 years of age); and current grade of cough \< 3 4. Ability of a parent or guardian to understand and comply with the study procedures and be available for all study visits 5. Signed written informed consent by a parent or guardian
Exclusion criteria
1\. Treatment with any systemic antibiotic therapy within 7 days before the diagnosis of CAP 2. Initial therapy for CAP with combination antibiotic therapy * amoxicillin, amoxicillin/clavulanate or cefdinir plus one or more additional oral, intravenous, or intramuscular antibiotics 3. History of anaphylaxis or severe drug allergy to amoxicillin, if prescribed amoxicillin or amoxicillin/clavulanic acid; or oral cephalosporin antibiotics (except cefaclor), if prescribed cefdinir 4. Presence of concomitant bacterial infection that requires \> 5 days of antibiotic therapy 5. Radiographic findings (where applicable) of complicated pneumonia at presentation or any subsequent chest radiograph up to the time of enrollment * clinically significant pleural effusion, lung abscess, or pneumatocele 6. Hospitalization for pneumonia during Day -5 to -1 of antibiotic therapy for CAP * subjects who require serial clinical assessments, but are discharged within 24 hours will not be considered hospitalized and will not satisfy this exclusion criterion 7. Pneumonia due to S. aureus or group A streptococcus documented by positive blood culture or PCR, at the time of enrollment 8. History of pneumonia within the previous 6 months 9. History of persistent asthma within the previous 6 months or current acute asthma exacerbation * persistent asthma is defined as receiving daily asthma maintenance therapy such as inhaled corticosteroids, cromolyn, theophylline, or leukotriene receptor antagonists \-- acute asthma exacerbation is defined as receiving concomitant bronchodilator therapy and systemic corticosteroids 10. Provider-diagnosis of aspiration pneumonia, bronchiolitis, or bronchitis 11. Surgery or other invasive procedures of the upper or lower airway (e.g., bronchoscopy, laryngoscopy) with general anesthesia or hospitalization \</=7 days before diagnosis of CAP 12. History of an underlying chronic medical condition * including chronic heart disease, chronic lung disease (except asthma), congenital anomalies of the airways or lung, cystic fibrosis, chronic renal disease including nephrotic syndrome, protein-losing enteropathy of any cause, severe malnutrition, neurocognitive disorders, metabolic disorders (including phenylketonuria), or genetic disorders (note: genetic syndromes such as Down syndrome and Edwards Syndrome are excluded; however, children with genetic disorders (e.g., hemophilia) but who do not have a genetic syndrome may not satisfy this particular exclusion criterion; it is important that children with such genetic disorders do not have symptoms and/or comorbidities that would pose additional risk to them nor jeopardize the adequacy of study assessments.) 13. History of a condition that compromises the immune system * HIV infection, primary immunodeficiency, anatomic or functional asplenia; receipt of a hematopoietic stem cell or solid organ transplant at any time; receipt of immunosuppressive therapy including chemotherapeutic agents, biologic agents, antimetabolites or radiation therapy during the past 12 months; or daily use of systemic corticosteroids for more than 7 consecutive days during the past 14 days 14. Any other condition that in the judgment of the investigator precludes participation because it could affect the safety of the subject 15. Current enrollment in another clinical trial of an investigational agent 16. Previous enrollment in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Desirability of Outcome Ranking (DOOR) | Outcome Assessment Visit 1 (Study Day 8 +/- 2 days) | DOOR is a composite endpoint created using clinical outcomes from the first 5 days and at Outcome Assessment Visit #1 (OAV #1). It is based on adequate clinical response at OAV #1, solicited symptoms from first 5 days and number of days of antibiotics use for worsening pneumonia from the first 5 days of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resolution of Symptoms (a Component of DOOR) | Outcome Assessment Visit 1 (Study Day 8 +/- 2 days) | This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #1. |
| Adequate Clinical Response Rates (a Component of DOOR) | Outcome Assessment Visit 1 (Study Day 8 +/- 2 days) | Lack of adequate clinical response at OAV #1 is defined as the presence of a medically attended visit to an Emergency Department (ED) or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 5. |
| Desirability of Outcome Ranking (DOOR) | Outcome Assessment Visit 2 (Study Day 22 +/- 3 days) | DOOR is a composite endpoint created using clinical outcomes from the first 18 days and at Outcome Assessment Visit #2 (OAV #2). It is based on adequate clinical response at OAV #2, solicited symptoms from first 18 days and number of days of antibiotics use for worsening pneumonia from the first 18 days of the study. |
| Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | Outcome Assessment Visit 1 (Study Day 8 +/- 2 days) | This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 5 |
| Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | Outcome Assessment Visit 1 (Study Day 8 +/- 2 days) | This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 5 |
| Number of Participants Reporting Solicited Symptoms | Outcome Assessment Visit 1 (Study Day 8 +/- 2 days) | This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 5 |
Countries
United States
Participant flow
Recruitment details
Children, males and females, aged 6-71 months who are diagnosed with Community Acquired Pneumonia (CAP) and initially treated in outpatient clinics, urgent care facilities, and emergency departments were enrolled. Participants were enrolled between 02DEC2016 and 22NOV2019.
Participants by arm
| Arm | Count |
|---|---|
| Short Course Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo
Amoxicillin: Amoxicillin is an aminopenicillin antibiotic
Amoxicillin-clavulanate: A fixed-ratio combination of amoxicillin trihydrate, an aminopenicillin, and potassium clavulanate, a beta-lactamase inhibitor, used to treat a broad-spectrum of bacterial infections, especially resistant strains.
Cefdinir: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Placebo: Placebo | 192 |
| Standard Course Participants will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days
Amoxicillin: Amoxicillin is an aminopenicillin antibiotic
Amoxicillin-clavulanate: A fixed-ratio combination of amoxicillin trihydrate, an aminopenicillin, and potassium clavulanate, a beta-lactamase inhibitor, used to treat a broad-spectrum of bacterial infections, especially resistant strains.
Cefdinir: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. | 193 |
| Total | 385 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Became Ineligible After Enrollment | 2 | 1 |
| Overall Study | Enrolled but Treatment Not Administered | 6 | 4 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Short Course | Standard Course | Total |
|---|---|---|---|
| Age, Continuous | 34.6 months STANDARD_DEVIATION 16.6 | 36.8 months STANDARD_DEVIATION 17.8 | 35.7 months STANDARD_DEVIATION 17.2 |
| Age, Customized 24-71 Months | 137 Participants | 137 Participants | 274 Participants |
| Age, Customized < 24 Months | 55 Participants | 56 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 18 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 176 Participants | 173 Participants | 349 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Initial Antibiotic Amoxicillin | 176 Participants | 174 Participants | 350 Participants |
| Initial Antibiotic Amoxicillin Clavulanate | 10 Participants | 10 Participants | 20 Participants |
| Initial Antibiotic Cefdinir | 6 Participants | 9 Participants | 15 Participants |
| Initial Site of Treatment ED | 41 Participants | 40 Participants | 81 Participants |
| Initial Site of Treatment Out-Patient/Urgent Care | 151 Participants | 153 Participants | 304 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants | 51 Participants | 99 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 17 Participants | 32 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) White | 121 Participants | 118 Participants | 239 Participants |
| Region of Enrollment United States Arkansas Children's Hospital | 8 Participants | 5 Participants | 13 Participants |
| Region of Enrollment United States Children's Hospital of Philadelphia | 59 Participants | 63 Participants | 122 Participants |
| Region of Enrollment United States Children's Hospital of Pittsburgh | 67 Participants | 62 Participants | 129 Participants |
| Region of Enrollment United States Cincinnati Children's Hospital | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States Duke University | 23 Participants | 20 Participants | 43 Participants |
| Region of Enrollment United States University of Alabama at Birmingham-Pediatrics | 1 Participants | 6 Participants | 7 Participants |
| Region of Enrollment United States Vanderbilt University Medical Center | 16 Participants | 16 Participants | 32 Participants |
| Region of Enrollment United States Washington University | 16 Participants | 19 Participants | 35 Participants |
| Region of Enrollment United States | 192 participants | 193 participants | 385 participants |
| Sex: Female, Male Female | 97 Participants | 93 Participants | 190 Participants |
| Sex: Female, Male Male | 95 Participants | 100 Participants | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 192 | 0 / 193 |
| other Total, other adverse events | 98 / 192 | 98 / 193 |
| serious Total, serious adverse events | 0 / 192 | 0 / 193 |
Outcome results
Primary
Desirability of Outcome Ranking (DOOR)
DOOR is a composite endpoint created using clinical outcomes from the first 5 days and at Outcome Assessment Visit #1 (OAV #1). It is based on adequate clinical response at OAV #1, solicited symptoms from first 5 days and number of days of antibiotics use for worsening pneumonia from the first 5 days of the study.
Time frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
Population: Intent to Treat (ITT) Population: All randomized subjects that were still eligible on Day 1 of the study. Analysis of DOOR will use all subjects in the ITT population. Subjects with missing values of DOOR will have their values imputed. However, summaries of observed ordinal clinical response values presented below are based on complete data without imputation.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and no adverse events | 97 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with mild adverse events | 47 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with moderate adverse events | 14 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with severe adverse events | 0 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with persistent symptoms of fever, tachypnea, or cough | 10 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with ED/clinic visit but no hospitalization | 2 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with hospitalization | 0 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Death from any cause | 0 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Death from any cause | 0 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and no adverse events | 107 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with persistent symptoms of fever, tachypnea, or cough | 12 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with mild adverse events | 42 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with hospitalization | 0 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with moderate adverse events | 10 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with ED/clinic visit but no hospitalization | 1 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with severe adverse events | 2 Participants |
Comparison: Null: the sum of the probability that a subject assigned to the 5-day arm will have a higher DOOR (higher DOOR is a lower value and is superior) than if assigned to the 10-day arm plus one-half the probability of equal DOORs is 50% (i.e., no difference in DOOR).p-value: <0.00195% CI: [0.63, 0.75]Wilcoxon (Mann-Whitney)
Secondary
Adequate Clinical Response Rates (a Component of DOOR)
Lack of adequate clinical response at OAV #2 is defined as the presence of a medically attended visit to an ED or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 18.
Time frame: Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)
Population: Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | ED or Clinic Visit | 4 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Hospitalization | 0 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Receipt of Non-Study Antibiotic | 2 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Surgical Procedure | 0 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Lack of Adequate Clinical Response | 2 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Surgical Procedure | 0 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Lack of Adequate Clinical Response | 3 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | ED or Clinic Visit | 2 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Receipt of Non-Study Antibiotic | 3 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Hospitalization | 0 Participants |
Secondary
Adequate Clinical Response Rates (a Component of DOOR)
Lack of adequate clinical response at OAV #1 is defined as the presence of a medically attended visit to an Emergency Department (ED) or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 5.
Time frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
Population: Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | ED or Clinic Visit | 2 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Hospitalization | 0 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Receipt of Non-Study Antibiotic | 2 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Surgical Procedure | 0 Participants |
| Short Course | Adequate Clinical Response Rates (a Component of DOOR) | Lack of Adequate Clinical Response | 2 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Surgical Procedure | 0 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Lack of Adequate Clinical Response | 1 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | ED or Clinic Visit | 1 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Receipt of Non-Study Antibiotic | 1 Participants |
| Standard Course | Adequate Clinical Response Rates (a Component of DOOR) | Hospitalization | 0 Participants |
Secondary
Desirability of Outcome Ranking (DOOR)
DOOR is a composite endpoint created using clinical outcomes from the first 18 days and at Outcome Assessment Visit #2 (OAV #2). It is based on adequate clinical response at OAV #2, solicited symptoms from first 18 days and number of days of antibiotics use for worsening pneumonia from the first 18 days of the study.
Time frame: Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)
Population: ITT Population: All randomized subjects that were still eligible on Day 1 of the study. Analysis of DOOR will use all subjects in the ITT population. Subjects with missing values of DOOR will have their values imputed. However, summaries of observed ordinal clinical response values presented below are based on complete data without imputation.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and no solicited events | 73 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with mild solicited events | 53 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with moderate solicited events | 25 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with severe solicited events | 3 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with persistent symptoms of fever, tachypnea, or cough | 7 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with ED/clinic visit but no hospitalization | 2 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with hospitalization | 0 Participants |
| Short Course | Desirability of Outcome Ranking (DOOR) | Death from any cause | 0 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Death from any cause | 0 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and no solicited events | 81 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with persistent symptoms of fever, tachypnea, or cough | 8 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with mild solicited events | 51 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with hospitalization | 0 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with moderate solicited events | 20 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Lack of adequate clinical response with ED/clinic visit but no hospitalization | 3 Participants |
| Standard Course | Desirability of Outcome Ranking (DOOR) | Adequate clinical response with resolution of symptoms and with severe solicited events | 4 Participants |
Comparison: Null: the sum of the probability that a subject assigned to the 5-day arm will have a higher DOOR (higher DOOR is a lower numerical value and is superior) than if assigned to the 10-day arm plus one-half the probability of equal DOORs is 50% (i.e., no difference in DOOR).p-value: <0.00195% CI: [0.57, 0.69]Wilcoxon (Mann-Whitney)
Secondary
Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits
This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 18
Time frame: Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)
Population: Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | ED or Clinic Visit | 29 Participants |
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | Receipt of Non-Study Antibiotic | 18 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | ED or Clinic Visit | 32 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | Receipt of Non-Study Antibiotic | 11 Participants |
Secondary
Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits
This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 5
Time frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
Population: Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | ED or Clinic Visit | 8 Participants |
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | Receipt of Non-Study Antibiotic | 7 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | ED or Clinic Visit | 7 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits | Receipt of Non-Study Antibiotic | 2 Participants |
Secondary
Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits
This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 5
Time frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
Population: Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | ED or Clinic Visit | 2 Participants |
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | Receipt of Non-Study Antibiotic | 2 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | ED or Clinic Visit | 1 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | Receipt of Non-Study Antibiotic | 1 Participants |
Secondary
Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits
This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 18
Time frame: Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)
Population: Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | ED or Clinic Visit | 4 Participants |
| Short Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | Receipt of Non-Study Antibiotic | 2 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | ED or Clinic Visit | 2 Participants |
| Standard Course | Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits | Receipt of Non-Study Antibiotic | 3 Participants |
Secondary
Number of Participants Reporting Solicited Symptoms
This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 18
Time frame: Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)
Population: Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Number of Participants Reporting Solicited Symptoms | Vomiting | 19 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Allergic Reaction | 22 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Irritability | 67 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Stomatitis | 1 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Diarrhea | 33 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Candidiasis | 7 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Any Event | 91 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Candidiasis | 7 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Any Event | 89 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Irritability | 60 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Vomiting | 24 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Diarrhea | 30 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Allergic Reaction | 21 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Stomatitis | 6 Participants |
Secondary
Number of Participants Reporting Solicited Symptoms
This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 5
Time frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
Population: Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Number of Participants Reporting Solicited Symptoms | Vomiting | 11 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Allergic Reaction | 15 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Irritability | 52 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Stomatitis | 1 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Diarrhea | 23 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Candidiasis | 4 Participants |
| Short Course | Number of Participants Reporting Solicited Symptoms | Any Event | 74 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Candidiasis | 4 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Any Event | 68 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Irritability | 43 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Vomiting | 11 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Diarrhea | 21 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Allergic Reaction | 15 Participants |
| Standard Course | Number of Participants Reporting Solicited Symptoms | Stomatitis | 3 Participants |
Secondary
Resolution of Symptoms (a Component of DOOR)
This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #1.
Time frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
Population: Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Resolution of Symptoms (a Component of DOOR) | Fever | 2 Participants |
| Short Course | Resolution of Symptoms (a Component of DOOR) | Cough | 7 Participants |
| Short Course | Resolution of Symptoms (a Component of DOOR) | Elevated respiratory rate | 2 Participants |
| Short Course | Resolution of Symptoms (a Component of DOOR) | Lack of Resolution of Symptoms | 12 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Lack of Resolution of Symptoms | 13 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Fever | 1 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Elevated respiratory rate | 7 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Cough | 4 Participants |
Secondary
Resolution of Symptoms (a Component of DOOR)
This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #2.
Time frame: Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)
Population: Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Short Course | Resolution of Symptoms (a Component of DOOR) | Lack of Resolution of Symptoms | 9 Participants |
| Short Course | Resolution of Symptoms (a Component of DOOR) | Fever | 0 Participants |
| Short Course | Resolution of Symptoms (a Component of DOOR) | Elevated respiratory rate | 2 Participants |
| Short Course | Resolution of Symptoms (a Component of DOOR) | Cough | 6 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Cough | 5 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Lack of Resolution of Symptoms | 11 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Elevated respiratory rate | 1 Participants |
| Standard Course | Resolution of Symptoms (a Component of DOOR) | Fever | 3 Participants |