Trial Outcomes & Findings for Treatment of Preschool Children With Upper Respiratory Tract Illnesses Using Azythromycin and Lower Respiratory Tract Symptoms Using Oral Corticosteroids. (NCT NCT01272635)

Last Updated: 2016-12-28

Results Overview

Progression to clinically significant lower respiratory tract symptoms defined by: (1) having symptoms that were more than mild after 3 albuterol administrations over 1 hour, or (2) requiring albuterol administrations more often than once every 4 hours, or (3) requiring more than 6 albuterol treatments over a 24-hour period, or (4) having moderate to severe cough or wheeze for 5 or more days since study medication was initiated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

607 participants

Primary outcome timeframe

14 days after initiation of APRIL therapy

Results posted on

2016-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	Azithromycin/Prednisolone Active Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Active Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day	Azithromycin/Placebo Active Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Placebo Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day	Placebo/Prednisolone Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Active Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day	Placebo/Placebo Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Placebo Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Overall Study STARTED	153	154	148	152
Overall Study COMPLETED	122	134	117	129
Overall Study NOT COMPLETED	31	20	31	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Azithromycin/Prednisolone Active Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Active Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day	Azithromycin/Placebo Active Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Placebo Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day	Placebo/Prednisolone Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Active Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day	Placebo/Placebo Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day Placebo Prednisolone: Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Overall Study Lost to Follow-up	31	20	31	23

Baseline Characteristics

Treatment of Preschool Children With Upper Respiratory Tract Illnesses Using Azythromycin and Lower Respiratory Tract Symptoms Using Oral Corticosteroids.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Azythromycin n=307 Participants Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=300 Participants Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Total n=607 Participants Total of all reporting groups
Age, Continuous	41.9 months STANDARD_DEVIATION 16.5 • n=5 Participants	41.1 months STANDARD_DEVIATION 16.4 • n=7 Participants	41.5 months STANDARD_DEVIATION 16.5 • n=5 Participants
Gender Female	124 Participants n=5 Participants	118 Participants n=7 Participants	242 Participants n=5 Participants
Gender Male	183 Participants n=5 Participants	182 Participants n=7 Participants	365 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	91 Participants n=5 Participants	92 Participants n=7 Participants	183 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	216 Participants n=5 Participants	208 Participants n=7 Participants	424 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	80 Participants n=5 Participants	77 Participants n=7 Participants	157 Participants n=5 Participants
Race (NIH/OMB) White	177 Participants n=5 Participants	185 Participants n=7 Participants	362 Participants n=5 Participants
Race (NIH/OMB) More than one race	40 Participants n=5 Participants	30 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	307 participants n=5 Participants	300 participants n=7 Participants	607 participants n=5 Participants
Urgent care or ED visits in prior year	2.5 visits STANDARD_DEVIATION 1.7 • n=5 Participants	2.5 visits STANDARD_DEVIATION 1.6 • n=7 Participants	2.5 visits STANDARD_DEVIATION 1.6 • n=5 Participants
Wheezing episodes in prior year	4.5 episodes STANDARD_DEVIATION 3.4 • n=5 Participants	4.4 episodes STANDARD_DEVIATION 2.9 • n=7 Participants	4.5 episodes STANDARD_DEVIATION 3.2 • n=5 Participants
Hospitalizations for respiratory symptoms in prior year	1 Hospitalizations n=5 Participants	1 Hospitalizations n=7 Participants	1 Hospitalizations n=5 Participants

PRIMARY outcome

Timeframe: 14 days after initiation of APRIL therapy

Population: All participants who initiated APRIL therapy

Outcome measures

Outcome measures
Measure	Azythromycin n=223 Participants Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=220 Participants Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Progression to Clinically Significant Lower Respiratory Tract Symptoms	35 participants	57 participants

PRIMARY outcome

Timeframe: 36-72 hours after initiation of OCELOT therapy

Population: Participants who developed severe lower respiratory tract infections and initiate blinded OCELOT therapy.

The Pediatric Respiratory Assessment Measure (PRAM) is a composite outcome with scores ranging from 0-12 with higher numbers representing worse symptoms. The score is calculated as the sum total of the follow five elements: (1) scalene retractions, (2) suprasternal retractions, (3) wheezing, (4) air entry, (5) oxygen saturation. A complete description can be found in: Ducharme FM, Chalut D, Plotnick L, et al. The Pediatric Respiratory Assessment Measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers. J Pediatr 2008;152:476-80.

Outcome measures

Outcome measures
Measure	Azythromycin n=23 Participants Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=21 Participants Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
OCELOT: Pediatric Respiratory Assessment Measure	0.82 PRAM score Standard Deviation 1.49	1.00 PRAM score Standard Deviation 1.41

SECONDARY outcome

Timeframe: 14 days after initiation of therapy

Population: Respiratory Tract Infections (RTI) progressing to Severe Lower RTI

Asthma related symptoms as measured by the parent-completed Pre-school Asthma Symptom Diary (PAD). The PAD was completed daily starting on the first day of an illness and continued until the participant was symptom-free for 2 days. It contains questions of frequency of respiratory symptoms, each scored on a scale of 1 through 7, with higher scores representing increasingly frequent symptoms, with daily scores ranging from 0 (asymptomatic) to a maximum of 102. The total PAD score is the sum of the daily individual symptom scores over the duration of the illness, with higher scores representing more frequent symptoms.

Outcome measures

Outcome measures
Measure	Azythromycin n=33 Participants Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=52 Participants Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Asthma Related Symptoms Among RTI Progressing to Severe LRTI	140 PAD score Standard Deviation 74	195 PAD score Standard Deviation 137

SECONDARY outcome

Timeframe: 14 days after initiation of therapy

Population: Data were of insufficient quality to be analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 14 days after initiation of therapy

Population: All participants who initiated APRIL therapy

Number of participants who had urgent care visits, ED visits, and/or hospitalizations for respiratory symptoms.

Outcome measures

Outcome measures
Measure	Azythromycin n=223 Participants Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=220 Participants Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Urgent Care Visits, ED Visits and Hospitalizations	20 participants	38 participants

SECONDARY outcome

Timeframe: 14 days after initiation of therapy

Parent-reported gastrointestinal symptoms during treated RTI.

Outcome measures

Outcome measures
Measure	Azythromycin n=307 Participants Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=300 Participants Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Drug Related Side Effects	3 events	1 events

Adverse Events

Azythromycin

Serious events: 18 serious events

Other events: 179 other events

Deaths: 0 deaths

Placebo

Serious events: 15 serious events

Other events: 180 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Azythromycin n=307 participants at risk Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=300 participants at risk Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Respiratory, thoracic and mediastinal disorders Asthma exacerbation	3.3% 10/307 • Number of events 10	3.7% 11/300 • Number of events 11
Respiratory, thoracic and mediastinal disorders Acute bronchitis/wheezing	0.65% 2/307 • Number of events 2	0.67% 2/300 • Number of events 2
Gastrointestinal disorders Abdominal pain	0.33% 1/307 • Number of events 1	0.00% 0/300
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/307	0.67% 2/300 • Number of events 2
Respiratory, thoracic and mediastinal disorders Influenza	0.33% 1/307 • Number of events 1	0.00% 0/300
Injury, poisoning and procedural complications Fracture	0.33% 1/307 • Number of events 1	0.00% 0/300
Injury, poisoning and procedural complications Salmonella	0.33% 1/307 • Number of events 1	0.00% 0/300
Infections and infestations Viral Enterocolitis	0.33% 1/307 • Number of events 1	0.00% 0/300
General disorders Complex Febrile Convulsion	0.33% 1/307 • Number of events 1	0.00% 0/300

Other adverse events

Other adverse events
Measure	Azythromycin n=307 participants at risk Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day	Placebo n=300 participants at risk Placebo Azithromycin: Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Respiratory, thoracic and mediastinal disorders Acute nasopharyngitis	17.6% 54/307 • Number of events 60	14.3% 43/300 • Number of events 47
Respiratory, thoracic and mediastinal disorders Acute Upper Respiratory Infection	24.4% 75/307 • Number of events 93	28.7% 86/300 • Number of events 98
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	9.4% 29/307 • Number of events 62	10.0% 30/300 • Number of events 59
Respiratory, thoracic and mediastinal disorders Cough	7.2% 22/307 • Number of events 79	9.0% 27/300 • Number of events 85

Additional Information

David Mauger

Penn State University

Phone: 717-531-7178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place