Procalcitonin to Reduce Antibiotic Use in Pediatric Pneumonia
Condition: Pneumonia; Pediatric Respiratory Diseases; Antibiotic Use; Community-acquired Pneumonia
MeSH terms: Pneumonia; Respiratory Tract Diseases; Respiration Disorders
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This pilot study will evaluate study processes and feasibility of a future large-scale
      clinical trial that proposes to test whether low-risk children managed as outpatients with
      community-acquired pneumonia (CAP) and procalcitonin (PCT) levels <0.25 ng/mL treated with
      placebo have a similar clinical response to those treated with antibiotics and fewer adverse
      effects.
    

Detailed description: 
      This pilot clinical trial is a 3-site, randomized, placebo-controlled, double-blinded trial
      assessing the feasibility of comparing amoxicillin to placebo in children 12 months to <6
      years of age who present to the ED with Community Acquired Pneumonia (CAP), a procalcitonin
      (PCT) concentration of <0.25 ng/mL, and who will be treated as outpatients.

      Screening and Enrollment This pilot feasibility trial will enroll over a 6-month period and
      take place at three sites (Ann and Robert H. Lurie Children's Hospital of Chicago, Cincinnati
      Children's Hospital Medical Center and The Children's Hospital of Philadelphia) that are or
      were members of the Pediatric Emergency Care Applied Research Network (PECARN). This study
      aims to enroll 36 patients in total (2 patients per month, per site). Clinical research
      coordinators (CRCs) at participating EDs will screen potentially eligible patients with
      respiratory tract symptoms and discuss eligibility with the treating attending physician. If
      thought to be eligible and a diagnosis of CAP is presumed by the treating physician, the CRC
      will approach the patient to complete screening procedures. The study will proceed in 2
      stages, each with its own informed consent process. During Stage 1, baseline characteristics
      and serum PCT levels will be ascertained. Stage 2 will consist of a randomized trial of
      amoxicillin vs. placebo in the subset of patients from Stage 1 that have PCT <0.25 ng/mL.

      Randomization After enrollment and confirmation of a PCT <0.25 ng/mL, patients will be
      randomized to a 10-day course of either amoxicillin (80-100 mg/kg divided BID up to 4,000
      mg/day) or placebo. Randomization to amoxicillin or placebo will be at a 1:1 ratio with block
      sizes of 2 and 4. Patients will be stratified by the clinical site and randomization will be
      performed through an online system. As a double-blind clinical trial, the study patients and
      their parents/guardians, investigators and study staff will be blinded to study treatment
      assignment for the duration of the study.

      Study Drug Administration Local investigational drug pharmacies will be provided with active
      study medication (i.e., amoxicillin) and matching placebo. Site pharmacies at each
      institution will store study drug and dispense as needed. Study medications will both be
      liquid reconstituted from powder, and will resemble each other with regards to appearance,
      favor, consistency and packaging. Study products will be labeled with numerical codes that
      will maintain allocation concealment. Site investigational pharmacies will be provided with
      amoxicillin and placebo, in addition to the randomization scheme. The pharmacy will aliquot
      amoxicillin and placebo into blinded bottles based on randomization scheme.

      Follow-up The guardians of participants will be asked to complete a daily symptom diary,
      using an online data collection form in REDCap, during the first 7 days after the initial
      Emergency Department study visit. The follow-up will assess patient condition, clinical
      response, signs or symptoms of clinical deterioration and other adverse effects. The primary
      outcome will be assessed at day 7 (+/- 2 days), using video chat technology that is standard
      on most smart phones, tablets, and computers. Video follow-up will be performed by site
      clinician investigators. In the rare case that a mobile device or computer with video chat
      technology is not available to the family, the day 7 follow-up will occur by telephone or
      text through an online system. A final follow-up, performed by site research staff, by
      telephone call, will occur at Day 21 (+/- 2 days) to assess overall disease course and
      secondary outcomes.

      Data Collection At baseline, demographics, medical history, and history of current illness
      will be obtained from all participants during stage 1 (pre-randomization). Vital signs will
      be obtained and a brief physical examination will be performed. After the initial ED visit,
      patients will record symptoms on daily basis for 6 days via an online data collection form.
      Follow-up assessments will be completed via telehealth visit or telephone for days 7 and 21.
      Follow-up visits will collect data regarding symptoms, adverse events and return to medical
      care, in addition to assessing adherence to study procedures (i.e., medication adherence and
      daily symptom diary completion). If there is concern for adverse events or deterioration that
      may warrant medical care, the participant's caregiver will be instructed to contact their
      primary care physician, emergency department, or call 911, as indicated.
    

Intervention name(s): Amoxicillin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Participants will be randomized to receive oral amoxicillin for a standard course (10 days); Participants will be randomized to receive oral placebo for a standard course (10 days)
Intervention MeSH terms: Amoxicillin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Pilot Feasibility Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Pediatrics; Pediatric CAP; Pediatric Pneumonia; Antibiotic Use