Rethinking Early Airway Clearence Therapies

N/ANot Yet RecruitingNCT07696338

Nicole Hamblett405 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 3 YearsMax age: 16 Years

Medical Language ↔ Plain English

Inclusion Criteria at Screening: * 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 Inclusion Criteria at Randomization: * 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 Exclusion Criteria at Screening: * 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 Exclusion Criteria at Visit 1: * 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)

Locations (39)

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

Birmingham, Alabama, United States

Tucson Cystic Fibrosis Center

Tucson, Arizona, United States

Childrens Hospital Los Angeles

Los Angeles, California, United States

CHOC Children's Hospital

Orange, California, United States

Stanford University Medical Center

Palo Alto, California, United States

Outcomes

Primary Outcomes

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).

Time frame: 52 weeks

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.

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).

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.

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).

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

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).

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.

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).

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.

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.

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.

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).

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.

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).

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.

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).

Time frame: 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).

Time frame: 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).

Time frame: 52 weeks

Rethinking Early Airway Clearence Therapies

Overview

Conditions

Interventions

Eligibility

Locations (39)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts