Streamlined Treatment of Pulmonary Exacerbations in Pedia... | NCT06654752

Status Module

Name	Class
Cystic Fibrosis Foundation	OTHER

Description Module

Detailed Description

The STOP PEDS pilot study demonstrated that a randomized trial of treatment strategies for mild pulmonary exacerbations (PEx) in children with CF was feasible and that assignment to a tailored therapy arm (defined below) may reduce antibiotic exposure.

Based on the research priorities identified by CF families and clinicians and the results of the pilot study, the STOP PEDS RCT is a multicenter, parallel, open label randomized controlled trial evaluating the long-term (one year) and short-term safety and efficacy of two antibiotic treatment strategies for the management of outpatient PEx in the pediatric CF population. The two treatment arms are immediate antibiotics and tailored therapy. In both arms, participants will be instructed to increase airway clearance at the onset of an eligible PEx. In the immediate antibiotics arm, they will also begin 14 days of oral antibiotics preselected by their primary CF providers, while in the tailored therapy they will only begin antibiotics if prespecified criteria for worsening symptoms or failure to improve are met.

The STOP PEDS study will enroll three cohorts. In the main cohort, children ages 6-18 on highly effective modulator therapy (HEMT) will be enrolled when well and followed for 12 months. Participants will be randomly assigned to a treatment arm and maintain that treatment assignment for all subsequent eligible PEx during their 12-month enrollment period. Two additional pilot cohorts, the preschool cohort (children ages 3 to 5 on HEMT) and the non-HEMT cohort (children ages 6-18 not eligible for HEMT), will be enrolled in parallel pilot studies. Participants will enroll when well and be followed through one randomized PEx.

Participants in the STOP PEDS RCT at selected sites will have the opportunity to enroll in optional substudies if eligible. These substudies include:

Clinic throat swab substudy
Home throat and nasal swab substudy
Remote monitoring substudy (Home monitoring of lung function, vital signs, activity and sleep)

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Immediate Antibiotics	Experimental	Increased airway clearance plus early initiation of oral antibiotics	Other: Immediate Oral Antibiotics
Tailored Therapy	Experimental	Increased airway clearance alone, with addition of oral antibiotics for worsening symptoms or failure to improve	Other: Tailored Treatment: Oral Antibiotics only if Additional Treatment needed

Name	Type	Description	Arm Group Labels	Other Names
Immediate Oral Antibiotics	Other	Increase airway clearance and start 14 days of preselected oral antibiotics right away	Immediate Antibiotics

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
One-year change in pulmonary function by spirometry-measured ppFEV1	Compare the difference in pulmonary function between arms by evaluating change in spirometry-measured percent predicted forced expiratory volume (ppFEV1). A spirometry test measures the amount of air a person can forcibly exhale after a deep breath (forced vital capacity, or FVC) and the amount of air they can exhale in one second (forced expiratory volume in one second, or FEV1). A lower measured value compared to the reference value indicates lung disease.	1 year

Secondary Outcomes

Measure	Description	Time Frame
One-Year change in pulmonary function by LCI	Compare the difference in pulmonary function between arms by evaluating change in Lung Clearance Index (LCI). LCI increases when there is lung disease, which causes ventilation inhomogeneity. LCI is calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal nitrogen concentration to 1/40th of the original level.

Other Outcomes

Measure	Description	Time Frame
Recovery to baseline by ppFEV1 and CRISS following a PEx	Compare recovery to baseline between arms over the 28-day period after the first pulmonary exacerbation (PEx), by spirometry-measured percent predicted forced expiratory volume (ppFEV1), and after all pulmonary exacerbations, measured by CRISS symptom scores. The Chronic Respiratory Infection Symptom Score (CRISS) ranges from 0 to 100, with higher scores indicating more symptoms.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age
1. For main cohort and non-HEMT cohort: age 6 to <19 years
2. For preschool cohort: age 3 to <6 years
Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
1. sweat chloride ≥ 60 mEq/liter
2. two disease-causing variants in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability of participant to comply with the requirements of the study
Highly Effective Modulator Therapy
1. For main cohort and preschool cohort: Taking HEMT for at least 3 months at enrollment
2. For non-HEMT cohort: not eligible for HEMT based on CFTR genotype or eligible but not taking for at least 3 months and no plans to start HEMT in the next year, and also not taking tezacaftor-ivacaftor or lumacaftor-ivacaftor for at least 3 months
For main cohort and non-HEMT cohort: able to perform acceptable and reproducible spirometry
For main cohort and non-HEMT cohort: ppFEV1 ≥ 50% predicted at enrollment based on the Global lung Initiative (GLI) reference equations
Ability to receive text messages and access the internet

Exclusion Criteria:

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the individual or the quality of the data
Receiving an acute course of oral or IV antibiotics at the time of enrollment or within the 14 days prior to enrollment. Individuals may be re-screened ≥21 days after completion of antibiotics if they are at their baseline state of health, per self-report
Treatment with systemic corticosteroids at enrollment or within the 14 days prior to enrollment. Individuals may be re- screened ≥21 days after completion of systemic corticosteroids if they are at their clinical baseline, per self-report
History of solid organ transplant
History of positive culture for Mycobacterium abscessus in the 12 months prior to enrollment
Treatment with antibiotics for any non-tuberculous mycobacteria (NTM) at enrollment
Three or more IV antibiotic-treated PEx in the 12 months prior to enrollment
Treatment with chronic oral antibiotics other than azithromycin at enrollment
Treatment with systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA) in the 12 months prior to enrollment

Name	Affiliation	Role
D. B. Sanders, MD, MS	Indiana University	Principal Investigator
Margaret Rosenfeld, MD, MPH	Seattle Children's Hospital	Principal Investigator

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases