(142) The STOP PEDS Pilot Study of Oral Antibiotic Timing in Pediatric CF Pulmonary Exacerbations

Background: Optimizing pulmonary exacerbations (PEx) management is a top research priority for the CF community. Several reports support more aggressive use of oral antibiotics for the treatment of PEx symptoms. On the other hand, particularly in children with relatively preserved lung health, milder exacerbations are frequently virally-driven, self-limited, and may not always require oral antibiotics, particularly in the era of highly effective modulator therapy.

STOP PEDS (Streamlined Treatment of Pulmonary exacerbations in Pediatrics) is an ongoing, multicenter, pilot study evaluating feasibility and acceptability of randomization to 1 of 2 arms for management of mild PEx within 1-7 days of symptom onset: early oral antibiotics (initiation at randomization + airway clearance) versus tailored therapy (airway clearance alone at randomization, with oral antibiotics initiated for worsening cough, cough not improving within 7 days, or cough not resolved by 14 days).

Methods: Prospective, multicenter, randomized, unblinded study enrolling children with CF ages 6-18 years at a time of clinical stability who are followed through one randomized PEx, or up to 18 months. Parents receive a text message weekly to report new cough. For mild PEx meeting pre-specified criteria, children are eligible for randomization to the early antibiotics or tailored therapy arm. Participants with a randomized PEx are followed for 28 days and then exit the study. The study team contacts the participant at defined intervals following randomization, and treatment is escalated (i.e., antibiotics are started for the “tailored therapy” arm, and participants return to clinical care in the “early antibiotic” arm) for pre-specified criteria, or upon request of the participant/family. All study procedures can be conducted remotely. The primary objective is to estimate the proportion of participants randomized to the tailored therapy arm that avoids antibiotics during the 28-day PEx period. We report cohort characteristics and feasibility metrics as of March 2022. Complete results will be available in summer 2022 and will be presented at the conference.

Results: 120 children were enrolled at 10 study sites between Nov 2020 and Dec 2021; 65% were on highly effective modulators, 55% were 12-18 years old, 48% were male, 49% had grown MSSA, and 14% P. aeruginosa at their most recent culture. The mean (SD) baseline FEV1 at enrollment was 98 (16)% predicted.

As of March 2022, 84 participants reported at least one PEx, and 56 (goal= 80) PEx have been randomized after a mean (SD) of 87 (76) days of enrollment. Three randomized PEx were identified in clinic; the rest were reported remotely, unrelated to a clinic visit. 11 participants reported 12 PEx that met criteria for being too severe that were not randomized. 17 participants had 21 PEx that met criteria for randomization but were not randomized; parent or participant discomfort with randomization was the most common reason.

Conclusions: STOP PEDS completed enrollment and has randomized 70% of the goal PEx as of March 2022. The study has demonstrated the feasibility of enrollment, identification of PEx through weekly texts, randomization of PEx treatment, and adherence with study measures. Whether the study has met its primary objective will be evaluated in summer 2022.

Acknowledgements: This work was supported by CFF. The authors thank study sites, participants, and families.

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