Rethinking Early Airway Clearence Therapies

NCT07696338 | Not Yet Recruiting DMC

• 1 other identifier: REACT-IP-25
• Study Type: interventional
• Target: 405
• Locations: 2 countries
• Sites: 39

Brief Summary

The REACT trial consists of two parallel, randomized studies; the Hypertonic Saline Study and the Dornase Alfa Study. Health outcomes among people with cystic fibrosis (CF) have been steadily improving, most recently with the advent of highly effective modulator therapy (HEMT). While therapies like hypertonic saline (HS) and dornase alfa (DA) improved outcomes in the past, they are often burdensome. Now that almost 90% of the North American CF population is being treated with elexacaftor/tezacaftor/ivacaftor (ETI) or vanzacaftor/tezacaftor/deutivacaftor (VTD), this trial will evaluate whether these newer treatments make daily HS or DA unnecessary. The trial begins with a 6-week run-in period where participants continue ETI or VTD but stop using HS and DA. Eligible participants are then assigned to either the HS Study or the DA Study for one year. Within those groups, they are randomized to either daily use of HS or DA or as needed use only during respiratory illnesses. The study aims to find out if lung health is similar between children and teens taking HEMT who use HS or DA treatments daily and those who use HS or DA treatments only when they are sick.

Conditions

Cystic Fibrosis (CF)

Keywords

CF; Cystic Fibrosis; Multiple Breath Washout; MBW; Lung Clearance Index; LCI; People with CF; Hypertonic Saline; Dornase Alfa; Pulmozyme; Trikafta; Alyftrek; ETI; REACT; VTD

Outcome Measures

Primary Outcomes (1)

• Absolute Change in Lung Clearance Index (LCI) through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.

  Difference in the change in lung clearance index through Week 52, relative to Week 0, between hypertonic saline (HS) therapy arms (twice daily HS - as-needed HS Entire Concurrently Eligible (ECE) cohort) and between dornase alfa (DA) therapy arms (daily DA - as-needed DA ECE cohort). Participants included in the as-needed HS ECE are those who had a non-zero probability of being assigned to the HS Study and were randomized to either the as-needed HS arm (HS Study) or the as-needed DA arm (DA Study).

  52 weeks

Secondary Outcomes (10)

• Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.

  52 weeks

• Rate of Protocol-Defined Pulmonary Exacerbations (PEx) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.

  52 weeks

• Absolute Change in Respiratory Symptoms, as Measured by the Cystic Fibrosis Questionnaire - Revised Respiratory Domain (CFQ-R RD), through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms

  52 weeks

• Absolute Change in Lung Clearance Index (LCI) from Week 0 to Week 6 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.

  6 weeks

• Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) from Week 0 to Week 6 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.

  6 weeks

Study Arms (4)

As-Needed HS

EXPERIMENTAL

As-needed hypertonic saline (HS) therapy in the HS Study

Other: As-needed hypertonic saline (HS)

Daily HS

ACTIVE COMPARATOR

Twice daily hypertonic saline (HS) therapy in the HS Study

Other: Twice daily hypertonic saline (HS)

As-Needed DA

EXPERIMENTAL

As-needed dornase alfa (DA) therapy in the DA Study

Other: As-needed dornase alfa (DA)

Daily DA

ACTIVE COMPARATOR

Daily dornase alfa (DA) therapy in the DA Study

Other: Daily dornase alfa (DA)

Interventions

As-needed hypertonic saline (HS) OTHER

As-needed hypertonic saline (HS) therapy during the 52-week study period.

As-Needed HS

As-needed dornase alfa (DA) OTHER

As-needed dornase alfa (DA) therapy during the 52-week study period.

As-Needed DA

Daily dornase alfa (DA) OTHER

Daily dornase alfa (DA) during the 52-week study period.

Daily DA

Twice daily hypertonic saline (HS) OTHER

Twice daily hypertonic saline (HS) therapy during the 52-week study period. The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride).

Daily HS

Eligibility Criteria

• Age: 3 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All genders ≥ 3 and ≤ 16 years of age
• Documentation of a CF diagnosis
• If capable of completing spirometry, forced expiratory volume in 1 second (FEV1) ≥ 70 % predicted at the Screening Visit
• Clinically stable with no significant changes in health status within the 28 days prior to and including Screening Visit
• MBW test meets acceptability criteria at the Screening Visit
• On elexacaftor/tezacaftor/ivacaftor (ETI) or vanzacaftor/tezacaftor/deutivacaftor (VTD) for at least 90 days prior to and including Screening (modified dose permissible) and willing to continue daily use of either ETI or VTD for the duration of the study
• Clinically stable with no significant changes in health status for 28 days prior to Visit 1
• MBW test meets acceptability at Visit 1
• Completed at least 60% of weekly electronic treatment diaries
• Take at least one dose of ETI or VTD per weekly electronic treatment diaries

You may not qualify if:

• No use of an investigational drug within 28 days prior to and including Screening Visit
• No initiation of new chronic therapy (e.g., azithromycin, inhaled tobramycin, inhaled aztreonam) within 28 days prior to and including Screening Visit
• No acute use of antibiotics (oral, inhaled, or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 28 days prior to and including Screening Visit
• No antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and including the Screening Visit
• No acute use of antibiotics (oral, inhaled or IV), systemic corticosteroids, hypertonic saline, or dornase alfa for respiratory tract symptoms within 28 days prior to and including Visit 1
• No absolute decrease in FEV1 % predicted of ≥10% from the Screening Visit to Visit 1 (in participants who performed acceptable and reproducible spirometry at both visits)

Sponsors & Collaborators

• Nicole Hamblett: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (39)

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

Birmingham, Alabama, 35233, United States

Location

Tucson Cystic Fibrosis Center

Tucson, Arizona, 85724, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

CHOC Children's Hospital

Orange, California, 92868, United States

Location

Stanford University Medical Center

Palo Alto, California, 94025, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta and Emory University

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan, Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

The Minnesota Cystic Fibrosis Center

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Kansas City

Kansas City, Missouri, 64108, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

University of Rochester Medical Center Strong Memorial

Rochester, New York, 14642, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Oregon Health & Sciences University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas Southwestern / Children's Health

Dallas, Texas, 75207, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Medical Group, Cystic Fibrosis Clinic - Pediatrics

Spokane, Washington, 99204, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

CF Centre BC Children's Hospital (Vancouver, Canada)

Vancouver, British Columbia, V6H3V4, Canada

Location

Queen Elizabeth II Hospital Halifax Adult CF Centre

Halifax, Nova Scotia, Canada

Location

CF Centre Hospital for Sick Children (Toronto, ON)

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Margaret Rosenfeld, MD, MPH

  University of Washington, Seattle Children's Research Institute

  PRINCIPAL INVESTIGATOR

• Felix Ratjen, MD, PhD

  University of Toronto, SickKids Research Institute

  PRINCIPAL INVESTIGATOR

• Jonathan Rayment, MDCM, MSc, FRCPC

  University of British Columbia, BC Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachael Buckingham

CONTACT

206-884-7517; rachael.buckingham@seattlechildrens.org

Anna Mead

CONTACT

anna.mead@seattlechildrens.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics, Division of Pulmonary and Sleep Medicine, UW School of Medicine Adjunct Professor, Biostatistics, UW School of Medicine Co-Executive Director, CF Therapeutics Development Network

Model Details: The REACT trial is a platform trial consisting of two parallel, randomized studies; the Hypertonic Saline (HS) Study and the (DA) Dornase Alfa Study. Participants will first be assigned to a given study based on their mucoactive therapy at screening. Those participants on no mucoactive therapy or HS only at screening will be assigned to the HS Study and participants on DA only at screening will be assigned to the DA Study. Those participants on both HS and DA at screening will be randomized to either the HS Study or the DA Study. Within a given study participants will be randomized to either an as-needed arm or a twice daily arm (HS Study)/daily arm (DA Study).

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (36)