Cystic Fibrosis (CF)REACTNCT07696338
Rethinking Early Airway Clearence Therapies
A study testing As-needed hypertonic saline (HS), Twice daily hypertonic saline (HS) and As-needed dornase alfa (DA) in people with Cystic Fibrosis (CF), run by Nicole Hamblett at 39 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 3 to 16 years
- Conditions the study is for
- Cystic Fibrosis (CF)
- What is being tested?
- As-needed hypertonic saline (HS), Twice daily hypertonic saline (HS) and As-needed dornase alfa (DA)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 405 participants
- Where
- 39 sitesin 2 countries
- Study dates
- 15 Sep 2026to 28 Feb 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
39 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Anna Mead contact
39 sites in 2 countries
United States36 sites
University of Michigan, Michigan Medicine
Ann Arbor, Michigan, 48109
Dawn Kruse, 734-615-3266, dmkruse@med.umich.edu
Children's Healthcare of Atlanta and Emory University
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
John Hopkins Hospital
Baltimore, Maryland, 21287
The Children's Hospital Alabama, University of Alabama at Birmingham
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
General Contact, cfclinicalresearch@med.unc.edu
Medical University of South Carolina
Charleston, South Carolina, 29425
Sarah Shine, shinesa@musc.edu
University of Virginia
Charlottesville, Virginia, 22904
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Mary Riordan, MRiordan@luriechildrens.org
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern / Children's Health
Dallas, Texas, 75207
Dayton Children's Hospital
Dayton, Ohio, 45404
Baylor College of Medicine
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Kansas City
Kansas City, Missouri, 64108
Jana Lamonte, 816-302-6308, jblomonte@cmh.edu
Childrens Hospital Los Angeles
Los Angeles, California, 90027
University of Wisconsin
Madison, Wisconsin, 53792
Children's Wisconsin
Milwaukee, Wisconsin, 53226
Laura Roth, 414-266-3856, lroth@mcw.edu
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Elizabeth Franck Thompson, 612-813-6347, elizabeth.franckthompson@childrensmn.org
The Minnesota Cystic Fibrosis Center
Minneapolis, Minnesota, 55455
CHOC Children's Hospital
Orange, California, 92868
Stanford University Medical Center
Palo Alto, California, 94025
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Adrienne DeRicco, adrienne.dericco2@upmc.edu
Oregon Health & Sciences University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23219
University of Rochester Medical Center Strong Memorial
Rochester, New York, 14642
Seattle Children's Hospital
Seattle, Washington, 98105
Dawn Batchuluun, 206-987-0806, Dawn.Batchuluun@seattlechildrens.org
Providence Medical Group, Cystic Fibrosis Clinic - Pediatrics
Spokane, Washington, 99204
Lauren Wilcox, 509-474-3836, lauren.wilcox@providence.org
St. Louis Children's Hospital
St Louis, Missouri, 63110
All Children's Hospital
St. Petersburg, Florida, 33701
Tucson Cystic Fibrosis Center
Tucson, Arizona, 85724
Canada3 sites
Queen Elizabeth II Hospital Halifax Adult CF Centre
Halifax, Nova Scotia
Andrea Dale, 302-456-0984, AndreaM.Dale@nshealth.ca
CF Centre Hospital for Sick Children (Toronto, ON)
Toronto, Ontario, M5G1X8
Stephanie Jeanneret-Manning, 416-813-4903, stephanie.jeanneretmanning@sickkids.ca
CF Centre BC Children's Hospital (Vancouver, Canada)
Vancouver, British Columbia, V6H3V4
Nazifaa Vasaya, nazifaa.vasaya@cw.bc.ca
About this study
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.
Read the detailed description
Health outcomes among people with cystic fibrosis (CF) have been steadily improving for decades through guideline-directed multi-disciplinary clinical care models, expanding CF-specific therapies, and, most recently, the advent of highly effective modulator therapies (HEMT). Chronic therapies such as hypertonic saline (HS) and dornase alfa (DA) were associated with improved outcomes in the pre-modulator era but are also burdensome and costly. Now that almost 90% of the North American CF population is being treated with elexacaftor/tezacaftor/ivacaftor (ETI) or vanzacaftor/tezacaftor/deutivacaftor (VTD), many in the CF community are asking if chronic inhaled therapies such as HS or DA can be stopped or not started (in young children). Indeed, many people with CF stably on ETI are already stopping or reducing these chronic inhaled mucoactive therapies (CIMT) without an evidence base to guide shared decision-making.
The REACT trial is a platform trial consisting of two parallel prospective, multicenter, randomized, open-label studies: the Hypertonic Saline (HS) Study and the Dornase Alfa (DA) Study. In the Hypertonic Saline (HS) Study, participants will be randomized to twice-daily inhaled HS or as-needed HS (with acute respiratory illnesses, if considered indicated) for one year. In the Dornase Alfa (DA) Study, participants will be randomized to daily inhaled DA or as-needed DA (with acute respiratory illnesses, if considered indicated) for one year.
Study participation will begin with a 6-week run-in period, during which participants who currently use HS, DA, or both will be instructed to stop these therapies; those who do not use chronic inhaled mucoactive therapies (CIMT) will be instructed to remain off these therapies. At the end of the run-in, eligible participants will be enrolled and assigned first to the HS or DA Study and then randomized to study arm. Participants who use only HS or no CIMT at study entry will be assigned to the HS Study. Those who use DA only at study entry will be assigned to the DA Study. Those who use both HS and DA will be randomly assigned to the HS or DA Study. Participants will be instructed to continue their mechanical airway clearance and inhaled antibiotics (if applicable) as prescribed at study entry. Those who were on both HS and DA at study entry will be instructed to only use the inhaled mucoactive agent to which they have been assigned (HS or DA). Participants randomized to the as-needed arm will be allowed to use the study inhaled agent (HS or DA) temporarily, if considered indicated, with acute respiratory illnesses. Participants in either arm will be allowed to (re)introduce chronic daily therapy if felt to be indicated by the treating physician.
- Conditions
- Cystic Fibrosis (CF)
- Being tested
- As-needed hypertonic saline (HS), Twice daily hypertonic saline (HS), As-needed dornase alfa (DA), Daily dornase alfa (DA)
- 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
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
As-needed hypertonic saline (HS)Other
As-needed hypertonic saline (HS) therapy during the 52-week study period.
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).
As-needed dornase alfa (DA)Other
As-needed dornase alfa (DA) therapy during the 52-week study period.
Daily dornase alfa (DA)Other
Daily dornase alfa (DA) during the 52-week study period.
| Study group | Role | What they receive |
|---|---|---|
| As-Needed HS | Experimental | As-needed hypertonic saline (HS) therapy in the HS Study Receives: Other: As-needed hypertonic saline (HS) |
| Daily HS | Active comparator | Twice daily hypertonic saline (HS) therapy in the HS Study Receives: Other: Twice daily hypertonic saline (HS) |
| As-Needed DA | Experimental | As-needed dornase alfa (DA) therapy in the DA Study Receives: Other: As-needed dornase alfa (DA) |
| Daily DA | Active comparator | Daily dornase alfa (DA) therapy in the DA Study Receives: Other: Daily dornase alfa (DA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Difference in the change in percent predicted forced expiratory volume in 1 second 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).
Measured: 52 weeks
Rate of Protocol-Defined Pulmonary Exacerbations (PEx) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Difference in the rate of protocol-defined pulmonary exacerbations (PEx) through Week 52 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).
Measured: 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
Difference in the change in the Cystic Fibrosis Questionnaire - Revised Respiratory Domain (CFQ-R RD) 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).
Measured: 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.
Difference in the change in the lung clearance index (LCI) from Week 0 to Week 6 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).
Measured: 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.
Difference in the change in the percent predicted forced expiratory volume in 1 second (ppFEV1) from Week 0 to Week 6 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.
Measured: 6 weeks
Absolute Change in Respiratory Symptoms, as Measured by the Cystic Fibrosis Questionnaire - Revised Respiratory Domain (CFQ-R RD), from Week 0 to Week 6 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Difference in the change in the Cystic Fibrosis Questionnaire - Revised Respiratory Domain (CFQ-R RD) from Week 0 to Week 6 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).
Measured: 6 weeks
Absolute Change in Treatment Burden, as Measured by the Cystic Fibrosis Questionnaire - Revised Treatment Burden Domain, through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Difference in the change in the Cystic Fibrosis Questionnaire - Revised Treatment Burden domain 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).
Measured: 52 weeks
Absolute Change in Family Impact, as Measured by the Pediatric Quality of Life Inventory (PedsQL) Family Impact Module, through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Difference in the change in the Pediatric Quality of Life Inventory (PedsQL) Family Impact Module 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).
Measured: 52 weeks
Healthcare Resource Utilization (HCRU) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Difference in the Healthcare Resource Utilization (HCRU) through Week 52 between hypertonic saline (HS) therapy arms (twice daily HS - as-needed HS) and between dornase alfa (DA) therapy arms (daily DA - as-needed DA).
Measured: 52 weeks
Incremental cost-effectiveness ratios (ICERs) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Difference in the change in the Incremental cost-effectiveness ratios (ICERs) through Week 52 between hypertonic saline (HS) therapy arms (twice daily HS - as-needed HS) and between dornase alfa (DA) therapy arms (daily DA - as-needed DA).
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study start15 Sep 2026 (estimated)
- Primary completion28 Feb 2030 (estimated)
- Study completion28 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic Fibrosis (CF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 405 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicole Hamblett
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor-investigator, Nicole Hamblett, Seattle Children's Hospital
- Investigators
- Margaret Rosenfeld, MD, MPH, Principal investigator, University of Washington, Seattle Children's Research InstituteFelix Ratjen, MD, PhD, Principal investigator, University of Toronto, SickKids Research InstituteJonathan Rayment, MDCM, MSc, FRCPC, Principal investigator, University of British Columbia, BC Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07696338
- Sponsor's protocol ID
- REACT-IP-25
- Acronym
- REACT
- Status last verified
- Jul 2026
- First submitted
- 6 Jul 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rethinking Early Airway Clearence Therapies
- ClinicalTrials.gov ID
- NCT07696338
- Acronym / sponsor ID
- REACT / REACT-IP-25
- Conditions
- Cystic Fibrosis (CF)
- Keywords
- CF, Cystic Fibrosis, Multiple Breath Washout, MBW, Lung Clearance Index, LCI, People with CF, Hypertonic Saline
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 405 participants (estimated)
- Lead sponsor
- Nicole HamblettUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- 15 Sep 2026 (estimated)
- Primary completion
- 28 Feb 2030 (estimated)
- Study completion
- 28 Feb 2030 (estimated)
- First posted
- 10 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Health outcomes among people with cystic fibrosis (CF) have been steadily improving for decades through guideline-directed multi-disciplinary clinical care models, expanding CF-specific therapies, and, most recently, the advent of highly effective modulator therapies (HEMT). Chronic therapies such as hypertonic saline (HS) and dornase alfa (DA) were associated with improved outcomes in the pre-modulator era but are also burdensome and costly. Now that almost 90% of the North American CF population is being treated with elexacaftor/tezacaftor/ivacaftor (ETI) or vanzacaftor/tezacaftor/deutivacaftor (VTD), many in the CF community are asking if chronic inhaled therapies such as HS or DA can be stopped or not started (in young children). Indeed, many people with CF stably on ETI are already stopping or reducing these chronic inhaled mucoactive therapies (CIMT) without an evidence base to guide shared decision-making.
The REACT trial is a platform trial consisting of two parallel prospective, multicenter, randomized, open-label studies: the Hypertonic Saline (HS) Study and the Dornase Alfa (DA) Study. In the Hypertonic Saline (HS) Study, participants will be randomized to twice-daily inhaled HS or as-needed HS (with acute respiratory illnesses, if considered indicated) for one year. In the Dornase Alfa (DA) Study, participants will be randomized to daily inhaled DA or as-needed DA (with acute respiratory illnesses, if considered indicated) for one year.
Study participation will begin with a 6-week run-in period, during which participants who currently use HS, DA, or both will be instructed to stop these therapies; those who do not use chronic inhaled mucoactive therapies (CIMT) will be instructed to remain off these therapies. At the end of the run-in, eligible participants will be enrolled and assigned first to the HS or DA Study and then randomized to study arm. Participants who use only HS or no CIMT at study entry will be assigned to the HS Study. Those who use DA only at study entry will be assigned to the DA Study. Those who use both HS and DA will be randomly assigned to the HS or DA Study. Participants will be instructed to continue their mechanical airway clearance and inhaled antibiotics (if applicable) as prescribed at study entry. Those who were on both HS and DA at study entry will be instructed to only use the inhaled mucoactive agent to which they have been assigned (HS or DA). Participants randomized to the as-needed arm will be allowed to use the study inhaled agent (HS or DA) temporarily, if considered indicated, with acute respiratory illnesses. Participants in either arm will be allowed to (re)introduce chronic daily therapy if felt to be indicated by the treating physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| As-Needed HS | Experimental | Other: As-needed hypertonic saline (HS)As-needed hypertonic saline (HS) therapy in the HS Study |
| Daily HS | Active comparator | Other: Twice daily hypertonic saline (HS)Twice daily hypertonic saline (HS) therapy in the HS Study |
| As-Needed DA | Experimental | Other: As-needed dornase alfa (DA)As-needed dornase alfa (DA) therapy in the DA Study |
| Daily DA | Active comparator | Other: Daily dornase alfa (DA)Daily dornase alfa (DA) therapy in the DA Study |
Who may qualify
- Ages
- 3 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| As-needed hypertonic saline (HS)As-needed hypertonic saline (HS) therapy during the 52-week study period. | Other | As-Needed HS |
| Twice daily hypertonic saline (HS)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). | Other | Daily HS |
| As-needed dornase alfa (DA)As-needed dornase alfa (DA) therapy during the 52-week study period. | Other | As-Needed DA |
| Daily dornase alfa (DA)Daily dornase alfa (DA) during the 52-week study period. | Other | Daily DA |
Primary outcome
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.
Time frame: 52 weeks
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).
10 secondary outcomes
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.
Time frame: 52 weeks
Rate of Protocol-Defined Pulmonary Exacerbations (PEx) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 6 weeks
Absolute Change in Respiratory Symptoms, as Measured by the Cystic Fibrosis Questionnaire - Revised Respiratory Domain (CFQ-R RD), from Week 0 to Week 6 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Time frame: 6 weeks
Absolute Change in Treatment Burden, as Measured by the Cystic Fibrosis Questionnaire - Revised Treatment Burden Domain, through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Time frame: 52 weeks
Absolute Change in Family Impact, as Measured by the Pediatric Quality of Life Inventory (PedsQL) Family Impact Module, through Week 52, Relative to Week 0, in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Time frame: 52 weeks
Healthcare Resource Utilization (HCRU) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Time frame: 52 weeks
Incremental cost-effectiveness ratios (ICERs) through Week 52 in Hypertonic Saline (HS Study) and Dornase Alfa (DA Study) Therapy Arms.
Time frame: 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Mead contact
Margaret Rosenfeld, MD, MPH principal investigator
University of Washington, Seattle Children's Research Institute
Felix Ratjen, MD, PhD principal investigator
University of Toronto, SickKids Research Institute
Jonathan Rayment, MDCM, MSc, FRCPC principal investigator
University of British Columbia, BC Children's Hospital
39 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing As-needed hypertonic saline (HS), Twice daily hypertonic saline (HS) and As-needed dornase alfa (DA) in people with Cystic Fibrosis (CF), run by Nicole Hamblett at 39 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rachael Buckingham (206-884-7517, rachael.buckingham@seattlechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.