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NCT06654752NARecruiting

Streamlined Treatment of Pulmonary Exacerbations in Pediatrics

University of Washington, the Collaborative Health Studies Coordinating Center

Start Date

12/1/2024

Completion Date

2/28/2029

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

Age Range: 3 years to 18 years

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 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 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

Interventions

OTHER

Immediate Oral Antibiotics

OTHER

Tailored Treatment: Oral Antibiotics only if Additional Treatment needed

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Conditions

Cystic Fibrosis

Locations

The Children's Hospital Alabama & University of Alabama at Birmingham

Birmingham, Alabama 35233

United States

Tucson Cystic Fibrosis Center

Tucson, Arizona 85713

United States

Children's Hospital of Los Angeles & Anton Yelchin Cystic Fibrosis Clinic

Los Angeles, California 90027

United States

Stanford University

Palo Alto, California 94304

United States

Rady Children's Hospital at University of California San Diego

San Diego, California 92123

United States

Children's Hospital of Colorado

Aurora, Colorado 80045

United States

Children's Healthcare of Atlanta & Emory University

Atlanta, Georgia 30322

United States

Ann & Robert H. Lurie Children's Hospital of Chicago & Northwestern University

Chicago, Illinois 60611

United States

Riley Hospital for Children & Indiana University

Indianapolis, Indiana 46202

United States

University of Iowa

Iowa City, Iowa 52242

United States

Johns Hopkins Hospital, Johns Hopkins University

Baltimore, Maryland 21287

United States

Boston Children's Hospital & Harvard University

Boston, Massachusetts 02115

United States

University of Michigan Health System

Ann Arbor, Michigan 48109-5212

United States

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota 55404

United States

The Minnesota Cystic Fibrosis Center & University of Minnesota

Minneapolis, Minnesota 55455

United States

Children's Mercy Hospital

Kansas City, Missouri 64108

United States

St. Louis Children's Hospital & Washington University School of Medicine

St Louis, Missouri 63110

United States

University of Rochester Medical Center Strong Memorial

Rochester, New York 14642

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27514

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

Oregon Health & Science University

Portland, Oregon 97239-3098

United States

Children's Hospital of Philadelphia & University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Children's Hospital of Pittsburgh of UPMC & University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15224

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

University of Texas Southwestern & Children's Health

Dallas, Texas 75235

United States

Texas Children's Hospital & Baylor College of Medicine

Houston, Texas 77030

United States

Vermont Children's Hospital & University of Vermont Medical Center

Burlington, Vermont 05401

United States

Virginia Commonwealth University

Richmond, Virginia 23298

United States

Seattle Children's Hospital

Seattle, Washington 98105

United States

University of Wisconsin

Madison, Wisconsin 53792

United States

Children's Wisconsin & Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

British Columbia Children's Hospital

Vancouver, British Columbia V6H 3V4

Canada

The Hospital for Sick Children & Toronto Canada CF Centre Pediatrics

Toronto, Ontario M5G 0A4

Canada