Clinical trial NCT04608019: Streamlined Treatment of Pulmonary Exacerbations in Pediatrics Pilot Study
Official title: Streamlined Treatment of Pulmonary Exacerbations in Pediatrics (Pilot)
Study type: INTERVENTIONAL
Overall status: COMPLETED
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: 2020-10-29
Enrollment: 121
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: STOP PEDS is a pilot study of children with CF ages 6-18 across 10 sites in North America. The primary goal is to assess the acceptability and feasibility of a multicenter randomized trial comparing immediate antibiotics versus tailored therapy for pulmonary exacerbation (PEx) treatment in this population.

Detailed description: STOP PEDS is a pilot study of children with CF ages 6-18 across 10 sites in North America. The primary goal is to assess the acceptability and feasibility of a multicenter randomized trial comparing immediate antibiotics versus tailored therapy for pulmonary exacerbation (PEx) treatment in this population. The primary endpoint is the proportion of participants in the tailored arm who did not take any oral antibiotics in the 28 days following randomization.

Ultimately, we want to learn:

* What is the best way to treat pulmonary exacerbations?
* Should everyone with a pulmonary exacerbation take antibiotics?
* Do the benefits of starting antibiotics at the first signs of illness outweigh the possible risks, like side effects and antibiotic resistance?

This pilot study is designed to determine if an interventional study to help answer these questions is feasible. Up to 120 participants will be enrolled and followed through their well state of health, then for 28 days following their first randomized exacerbation. Enrollment will stop after 80 pulmonary exacerbation events have been randomized, even if this does not require 120 participants. Due to the nature of the study, the identity of treatment assignment will be known to investigators, research staff, and patients (ie, not blinded).

Total duration of this pilot study is expected to be approximately 18 months: 6 months for participant recruitment and 12 months for follow up. Participants could be monitored for up to 18 months if they do not have an exacerbation. However, it is anticipated that the majority of participants will experience a randomizable PEx event and therefore have a shorter follow up period.

Eligibility criteria: Enrollment Inclusion Criteria:

1. Age 6 to \<19 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. Able to perform acceptable and reproducible spirometry
5. FEV1 ≥ 50% predicted at enrollment based on the Global lung Initiative (GLI) reference equations
6. At least 1 course of oral or IV antibiotics for respiratory symptoms since January 1, 2019.
7. Ability to receive text messages and access the internet

Enrollment Exclusion Criteria:

1. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
2. Previous randomization in the study
3. Receiving antibiotics for a PEx at the time of enrollment or within the 21 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.
4. Treatment with systemic corticosteroids at enrollment. Individuals may be re- screened ≥21 days after completion of systemic corticosteroids if they are at their clinical baseline, per self-report.
5. History of solid organ transplant
6. History of positive culture for Mycobacterium abscessus in the 12 months prior to enrollment
7. Treatment with antibiotics for any non-tuberculous mycobacteria (NTM) at enrollment
8. Three or more IV antibiotic-treated PEx in the 12 months prior to enrollment
9. Treatment with chronic oral antibiotics other than azithromycin at enrollment

Primary outcomes:
measure: Delayed antibiotics
timeFrame: 28 days
Secondary outcomes:
measure: Consent
timeFrame: 6 months
measure: Pulmonary Exacerbations Reported
timeFrame: 18 months
measure: Randomization Criteria
timeFrame: 18 months
measure: Participant Exacerbations
timeFrame: 18 months
measure: Randomized Exacerbations
timeFrame: 18 months
measure: Day 28 Follow-up
timeFrame: 18 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Cystic Fibrosis Center
state: Arizona
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago & Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital and Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Riley Children's Hospital, Indianapolis, IN
name: Donald B. Sanders, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital, Seattle, WA
name: Margaret Rosenfeld, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bradley J, McAlister O, Elborn S. Pulmonary function, inflammation, exercise capacity and quality of life in cystic fibrosis. Eur Respir J. 2001 Apr;17(4):712-5. doi: 10.1183/09031936.01.17407120.
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.