Short Versus Standard of Care Antibiotic Duration for Children Hospitalized for CAP

Official title

Short Versus Standard of Care Antibiotic Duration for Hospitalized Children With Uncomplicated Community-acquired Pneumonia: a Non-inferiority, Randomized Controlled Trial.

Overview

The goal of this open label, randomized, non-inferiority clinical trial is to compare the treatment success of a 5 day antibiotic course versus a standard antibiotic course (usually 7-14 days of antibiotics) in hospitalized children aged 3 months to 18 years, with uncomplicated community acquired pneumonia. The main questions it aims to answer are: * Does a 5 day course work as well as standard (longer) courses of antibiotics for treating community acquired pneumonia in children? * Does a 5 day course cause less antibiotic side effects compared to a standard (longer) course of antibiotics in children with community acquired pneumonia? Participants will * be randomly assigned to either receive 5 total days or a total duration decided by the treating physician * receive a brief follow up questionnaire regarding clinical symptoms, follow up care/antibiotics, and side effects via phone or email at days 5 and 14 from the start of antibiotics Researchers will compare the experimental group (receiving 5 days duration) with the control group (standard duration) to see if 5 days is as successful as a standard duration.

Detailed description

This is an open label, randomized, non-inferiority clinical trial to determine if a 5-day antibiotic course works as well compared to a standard antibiotic course (usually 7-10 days of antibiotics) in hospitalized children who are aged 3 months to less than 18 years old, with uncomplicated community acquired pneumonia.

We will recruit 150 participants meeting inclusion/exclusion criteria. Participants will be randomized to one of the study groups. In the experimental group, the participant will receive a total antibiotic course of 5 days. In the other group (control group), participants will receive the standard-of-care antibiotic course (the duration will be decided by the primary treating physician in this group). The selection of antibiotic therapy will be made by the treating physician, generally in accordance with the institutional clinical practice guideline on community acquired pneumonia, prior to enrollment in the study. Other medical care, aside from the treatment duration, will be the same and will be guided by the primary treating doctor. The primary treating doctor will also decide when the participant is medically ready for discharge from the hospital.

During the consenting process, a member of the research team will verify the contact numbers or email of the parent(s)/guardian of participant to be used after discharge for follow-up communication. Every participant's parent/guardian will receive a text message/email questionnaire on day 5 and day 14 after the start of antibiotics to assess for clinical improvement, side effect(s) to the antibiotics, recurrence of fever, or need for additional antibiotics or other medical care. Participants parent(s)/guardian will be contacted by phone for additional information if there is concern for a failure or significant medical concern.

The primary objective of this study is to compare the failure rate between a short course (5-days) and standard antibiotic course (usually 7-10 days of antibiotics) of antibiotics in hospitalized children with uncomplicated pneumonia. Failure will be defined as the clinical need for additional antibiotic treatment, emergency department visit or readmission to the hospital for a suspected lower respiratory tract infection within 14 days of treatment initiation.

The secondary objective will compare the rate of adverse drug events between short and long-course durations of antibiotic therapy in children hospitalized for CAP. Adverse drug events include any allergic reaction such as skin rash, itching or other and/or abdominal symptoms such as vomiting, stomach pain and diarrhea.

Data will be summarized by n (%) or mean and standard deviation (SD) or median and interquartile range (IQR). Continuous variables will be compared by t-test while categorical variables will be compared by Chi-square or Fisher's exact test. A 95% CI will be calculated for the difference in failure rate between the shorter antibiotic course (5-day) group and the standard course group. Non-inferiority will be declared if the 95% CI lies below 10%. P\<0.05 will be considered statistically significant. Data will be analyzed by SAS version 9.4 (SAS Institute Inc., Cary, NC) and SPSS version 28.0 (IBM Corp., Armonk, NY).

Interventions

• Drug Ampicillin for Injection
  Ampicillin is an intravenous antibiotic commonly used in the initial treatment of children hospitalized with community-acquired pneumonia.
• Drug Ceftriaxone for Injection
  Ceftriaxone is an intravenous antibiotic commonly used in the initial treatment of children hospitalized with community-acquired pneumonia.
• Drug Amoxicillin
  Amoxicillin is an oral antibiotic commonly used in the treatment of children hospitalized with community-acquired pneumonia to complete the antibiotic course after discharge.
• Drug Ampicillin / Sulbactam Injection
  Ampicillin/Sulbactam is an intravenous antibiotic commonly used in the initial treatment of children hospitalized with community-acquired pneumonia.
• Drug Amoxicillin-clavulanate
  Amoxicillin-clavulanate is an oral antibiotic commonly used in the treatment of children hospitalized with community-acquired pneumonia to complete the antibiotic course after discharge.
• Drug Clindamycin
  Clindamycin is an antibiotic that can be given intravenously or orally that is sometimes used in the treatment of children hospitalized or discharged with community-acquired pneumonia.
• Drug Cefprozil
  Cefprozil is an oral antibiotic sometimes used in the treatment of children hospitalized with community-acquired pneumonia to complete the antibiotic course after discharge.
• Drug Levofloxacin
  Levofloxacin is an antibiotic that can be given intravenously or orally that is sometimes used in the treatment of children hospitalized or discharged with community-acquired pneumonia.

Primary outcome measures

• Treatment failure rate [Time frame: 14 days from the first dose antibiotics]

Secondary outcome measures (1)

• Adverse drug event rate [Time frame: 14 days from the first dose antibiotics]

Eligibility criteria

Inclusion Criteria (ALL of the following must be met):

• Children aged 3 months to <18 years old
• Hospitalized in either the acute care or the pediatric intensive care units
• Clinically diagnosed with uncomplicated bacterial community acquired pneumonia (as determined by the treating physician)
• Radiological findings suggestive of pneumonia (such as consolidation, lobar or interstitial infiltrates)
• Achieved clinical stability within 72 hours from the first antibiotic dose (clinical stability includes being off supplemental oxygen/ventilatory support and temperature remaining < 38 Celsius).

Exclusion Criteria (presence of ANY of the following will exclude a potential participant):

• Hemodynamic instability at any point during hospitalization that required inotropic support
• Requirement of respiratory support > 72 hours
• Presence of a parapneumonic effusion >10 mm on decubitus x-ray or greater than ¼ of hemithorax opacified on chest imaging
• Need for chest tube placement
• Extrapulmonary involvement (ie: another infection located outside of the lungs) except for otitis media if the planned treatment is ≤ 5 days
• Pneumonia caused by known staphylococcus aureus identified from culture (blood, bronchoalveolar aspirate, tracheal aspirate, or pleural fluid)
• Antibiotic course started >72 hours after admission
• Antibiotics used for > 24 hours within the 2 weeks prior to admission
• Chronic respiratory illness other than asthma or reactive airway disease
• Immunocompromised patient (primary or secondary)
• Primary physician refusal
• Parent refusal
• Non-English speakers
• Pregnant or lactating female
• Participant will become ≥ 18 years old at or before the time of day 14 follow up
• Inability to adhere to follow up

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Childrens Wisconsin — Milwaukee

Identifiers

NCT: NCT06494072 · PRO00046965

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗