Clinical trial NCT06654752: Streamlined Treatment of Pulmonary Exacerbations in Pediatrics
Official title: Streamlined Treatment of Pulmonary Exacerbations in Pediatrics Randomized Controlled Trial (STOP PEDS RCT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
oral antibiotics
pulmonary exacerbation
pediatric
Lead sponsor: University of Washington, the Collaborative Health Studies Coordinating Center
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2024-10-23
Enrollment: 430
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 pulmonary exacerbations (PEx) in the pediatric CF population.

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)

Eligibility criteria: Inclusion Criteria:

1. Age

   1. For main cohort and non-HEMT cohort: age 6 to \<19 years
   2. For preschool cohort: age 3 to \<6 years
2. 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
3. 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
4. Highly Effective Modulator Therapy

   1. For main cohort and preschool cohort: Taking ETI or ivacaftor 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
5. For main cohort and non-HEMT cohort: able to perform acceptable and reproducible spirometry
6. For main cohort and non-HEMT cohort: ppFEV1 ≥ 50% predicted at enrollment based on the Global lung Initiative (GLI) reference equations
7. Ability to receive text messages and access the internet

Exclusion Criteria:

1. 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
2. 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
3. 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
4. History of solid organ transplant
5. History of positive culture for Mycobacterium abscessus in the 12 months prior to enrollment
6. Treatment with antibiotics for any non-tuberculous mycobacteria (NTM) at enrollment
7. Three or more IV antibiotic-treated PEx in the 12 months prior to enrollment
8. Treatment with chronic oral antibiotics other than azithromycin at enrollment
9. Treatment with systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA) in the 12 months prior to enrollment

Primary outcomes:
measure: One-year change in pulmonary function by spirometry-measured ppFEV1
timeFrame: 1 year
Secondary outcomes:
measure: One-Year change in pulmonary function by LCI
timeFrame: 1 year
Other outcomes:
measure: Recovery to baseline by ppFEV1 and CRISS following a PEx
timeFrame: 28 days
measure: Recovery to baseline by Lung Clearance Index (LCI)
timeFrame: 28 days
measure: Safety Endpoint 1: Cumulative oral antibiotic exposure
timeFrame: 1 year
measure: Safety Endpoint 2: Number of respiratory illnesses
timeFrame: 1 year
measure: Safety Endpoint 3: Proportion of respiratory illnesses treated with antibiotics during PEx
timeFrame: 28 days
measure: Safety Endpoint 4: Number of PEx treated with IV antibiotics
timeFrame: 1 year
measure: Safety Endpoint 5: Proportion of PEx failing to recover to baseline symptoms at Day 28
timeFrame: 28 days
measure: Safety Endpoint 6: Proportion of PEx with ppFEV1 below baseline at Day 28
timeFrame: 1 year
measure: Safety Endpoint 7: Time from initial randomized PEx to next respiratory illness
timeFrame: 1 year
measure: Safety Endpoint 8: Targeted adverse events (patient report of antibiotic side effects during PEx)
timeFrame: 1 year
measure: Safety Endpoint 9: Treatment-emergent CF microorganisms on clinical respiratory cultures
timeFrame: 1 year
measure: Qualitative Assessment 1: Caregivers' experience managing study treatment
timeFrame: 1 year
measure: Qualitative Assessment 2: Study treatment impact on child and family daily life
timeFrame: 1 year
measure: Health care costs 1: Total estimated cost of antibiotics
timeFrame: 1 year
measure: Health care costs 2: Health care utilization
timeFrame: 1 year
measure: Health care costs 3: Parent work productivity measures (WPAI)
timeFrame: 1 year
measure: Preschool and non-HEMT Pilot Cohort Primary Feasibility
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort Safety Endpoint 1: ppFEV1 and LCI recovery
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort Safety Endpoint 2: Time to symptom recovery
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort Safety Endpoint 3: Targeted adverse events
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort Safety Endpoint 4: Treatment-emergent CF microorganisms
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort Safety Endpoint 5: Treatment with additional non-protocol assigned antibiotics
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort Safety Endpoint 6: Time to IV antibiotics following a randomized PEx
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort: Future Larger Clinical Trial Feasibility 1
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort: Future Larger Clinical Trial Feasibility 2
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort: Future Larger Clinical Trial Feasibility 3
timeFrame: 28 days
measure: Preschool and non-HEMT Pilot Cohort: Future Larger Clinical Trial Feasibility 4
timeFrame: 28 days
measure: Clinic Throat Swab Substudy 1: Metagenomic Sequencing
timeFrame: 1 year
measure: Clinic Throat Swab Substudy 2: Microbiota Measures
timeFrame: 1 year
measure: Home Throat and Nasal Swab Substudy 1: Feasibility of Home Collection of Nasal Swabs for Viral Testing and Illness Frequency
timeFrame: 28 days
measure: Home Throat and Nasal Swab Substudy 2: Feasibility of Home Collection of Throat Swabs for Bacterial testing
timeFrame: 28 days
measure: Home Throat and Nasal Swab Substudy 3: Association Between Viral Illness and Symptom recovery
timeFrame: 28 days
measure: Home Throat and Nasal Swab Substudy 3: Association Between Viral Illness and FEV1
timeFrame: 28 days
measure: Home Throat and Nasal Swab Substudy 3: Association Between Viral Illness and antibiotic treatment.
timeFrame: 28 days
measure: Home Throat and Nasal Swab Substudy 5: Bacterial Pathogen Identification, Frequency and Impact on Treatment Changes
timeFrame: 28 days
measure: Remote Monitoring Substudy 1: Feasibility of Home Spirometry Use During PEx
timeFrame: 28 days
measure: Remote Monitoring Substudy 2: Feasibility of BioButton Use During PEx
timeFrame: 14 days
measure: Remote Monitoring Substudy 3: Change in FEV1 by Home Spirometry
timeFrame: 28 days
measure: Remote Monitoring Substudy 4: Compare Home Spirometry vs. Clinic Spirometry Measures
timeFrame: 28 days
measure: Remote Monitoring Substudy 5: BioButton-measured Change in Resting Heart Rate During PEx
timeFrame: 14 days
measure: Remote Monitoring Substudy 5: BioButton-measured Change in Resting respiratory rate During PEx
timeFrame: 14 days
measure: Remote Monitoring Substudy 5: BioButton-measured Change in Activity Level During PEx
timeFrame: 14 days
measure: Remote Monitoring Substudy 5: BioButton-measured Change in Sleep During PEx
timeFrame: 14 days
measure: Remote Monitoring Substudy 6: Compare BioButton-measured Change in resting heart rate During PEx with Baseline Averages
timeFrame: 14 days
measure: Remote Monitoring Substudy 6: Compare BioButton-measured Change in Resting respiratory rate During PEx with Baseline Averages
timeFrame: 14 days
measure: Remote Monitoring Substudy 6: Compare BioButton-measured Change in activity level During PEx with Baseline Averages
timeFrame: 14 days
measure: Remote Monitoring Substudy 6: Compare BioButton-measured Change in Sleep During PEx with Baseline Averages
timeFrame: 14 days
measure: Remote Monitoring Substudy 7: Determine correlations between changes in FEV1 and CRISS to Resting Heart Rate (HR)
timeFrame: 14 days
measure: Remote Monitoring Substudy 7: Determine correlations between changes in FEV1 and CRISS to Resting Respiratory rate
timeFrame: 14 days
measure: Remote Monitoring Substudy 7: Determine correlations between changes in FEV1 and CRISS to Activity level
timeFrame: 14 days
measure: Remote Monitoring Substudy 7: Determine correlations between changes in FEV1 and CRISS to Sleep duration
timeFrame: 14 days
Locations:
city: Birmingham
country: United States
facility: The Children's Hospital Alabama & University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Tucson Cystic Fibrosis Center
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles & Anton Yelchin Cystic Fibrosis Clinic
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital at University of California San Diego
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta & Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago & Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children & Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital, Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital & Harvard University
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: The Minnesota Cystic Fibrosis Center & University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital & Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester Medical Center Strong Memorial
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia & University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC & University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern & Children's Health
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital & Baylor College of Medicine
state: Texas
city: Burlington
country: United States
facility: Vermont Children's Hospital & University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Wisconsin & Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital for Sick Children & Toronto Canada CF Centre Pediatrics
state: Ontario
Study officials:
affiliation: Indiana University
name: D. B. Sanders, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Margaret Rosenfeld, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanders DB, Bartz TM, Zemanick ET, Hoppe JE, Hinckley Stukovsky KD, Cogen JD, Bendy L, McNamara S, Enright E, Kime NA, Kronmal RA, Edwards TC, Morgan WJ, Rosenfeld M. A Pilot Randomized Clinical Trial of Pediatric Cystic Fibrosis Pulmonary Exacerbations Treatment Strategies. Ann Am Thorac Soc. 2023 Dec;20(12):1769-1776. doi: 10.1513/AnnalsATS.202303-245OC.