Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy
- Conditions
- Cystic Fibrosis
- Interventions
- Other: Discontinuation of hypertonic saline (HS)Other: Discontinuation of dornase alfa (dnase)Other: Continuation of hypertonic saline (HS)Other: Continuation of dornase alfa (dnase)
- Registration Number
- NCT04378153
- Lead Sponsor
- Nicole Hamblett
- Brief Summary
Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating CF, it is still largely unknown whether or not other chronic therapies can be safely stopped. The SIMPLIFY study is being done to test whether or not it is safe to stop taking inhaled hypertonic saline or Pulmozyme® (dornase alfa) in those people that are also taking Trikafta™.
Trikafta (elexacaftor/tezacaftor/ivacaftor) is a combination CFTR modulator therapy that was approved by the Food and Drug Administration for people with CF who have at least one F508del mutation. The three drugs that make up Trikafta work together to allow many more chloride ions to move into and out of the cells, improving the balance of salt and water in the lungs. These changes result in better clearance of mucus from the lungs and improvements in lung function.
Inhaled hypertonic saline and Pulmozyme (dornase alfa) also improve clearance of mucus from the lungs to support lung function and have been available to people with CF for many years. Both therapies are considered to be relatively burdensome and it is not known whether either therapy can improve or maintain lung function above what is already gained through Trikafta use.
The goal of the SIMPLIFY study is to get information about whether or not it is safe to stop either inhaled hypertonic saline or Pulmozyme (dornase alfa) by testing if there is a change in lung function in subjects with cystic fibrosis (CF) who are assigned to stop their chronic medication (either hypertonic saline or Pulmozyme) as compared to those who are assigned to keep taking their medication while continuing to take Trikafta.
- Detailed Description
This master protocol is designed to evaluate the independent effects of discontinuing hypertonic saline (Study A) and dornase alfa (Study B) in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). Study A and Study B are identical open label two-arm randomized non-inferiority trials consisting of a 2-week screening period, randomization to continue or discontinue hypertonic saline (Study A) or dornase alfa (Study B), followed by a 6-week study period. Subjects taking only hypertonic saline (HS) or dornase alfa at trial entry will be randomized 1:1 to either continue or discontinue the applicable therapy (i.e. HS or dornase alfa). Subjects taking both hypertonic saline and dornase alfa at study entry will be randomized to participate in either Study A or Study B and will be randomized (1:1) to continue or discontinue the applicable therapy (i.e. HS or dornase alfa). After completion of the first study, eligible subjects may subsequently enroll in the alternative study.
Clinical outcomes (forced expiratory volume in 1 second \[FEV1\], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and the subject's perception of how stopping HS or dornase alfa (or both) would impact their daily life will be evaluated in all subjects. Additional outcome measurements will be conducted in a subset of subjects at selected study sites:
* Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI)
* Mucociliary Clearance (MCC) using inhaled radio-labeled particles to evaluate changes in mucociliary clearance
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 870
- Diagnosis of CF.
- Age ≥ 12 years at the Screening Visit.
- Forced expiratory volume in 1 second (FEV1) ≥ 70 % predicted at the Screening Visit if < 18 years old, and ≥ 60 % predicted at Screening Visit if ≥ 18 years old.
- Clinically stable with no significant changes in health status within the 7 days prior to and including the Screening Visit.
- Current treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the duration of the study.
- Currently taking hypertonic saline (at least 3%) and/or dornase alfa for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the 2-week screening period.
- Active smoking or vaping.
- Use of an investigational drug within 28 days prior to and including the Screening Visit.
- Changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, aztreonam lysine) within 28 days prior to and including the Screening Visit. This includes new airway clearance routines.
- Acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 7 days prior to and including the Screening Visit.
- Chronic use of systemic corticosteroids at a dose equivalent to ≥ 10mg per day of prednisone within 28 days prior to and including the Screening Visit.
- Antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and including the Screening Visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HS-Discontinue (Study A) Discontinuation of hypertonic saline (HS) Discontinuation of current hypertonic saline (HS) therapy in Study A Dnase-Discontinue (Study B) Discontinuation of dornase alfa (dnase) Discontinuation of current dornase alfa (dnase) therapy in Study B HS-Continue (Study A) Continuation of hypertonic saline (HS) Continuation of current hypertonic saline (HS) therapy in Study A Dnase-Continue (Study B) Continuation of dornase alfa (dnase) Continuation of current dornase alfa (dnase) therapy in Study B
- Primary Outcome Measures
Name Time Method Number of Participants Eligible to be Assessed for Sub-study Enrollment 2-week run-in period The number of participants completing the run-in period of the study and not meeting any of the exclusion criteria during the run-in period.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (80)
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Boston Children's Hospital, Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Monmouth Medical Center
🇺🇸Eatontown, New Jersey, United States
Saint Luke's Cystic Fibrosis Center of Idaho
🇺🇸Boise, Idaho, United States
New York Medical College at Westchester Medical Center
🇺🇸Valhalla, New York, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Maine Medical Partners Pediatric Specialty Care
🇺🇸Portland, Maine, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Tulane University
🇺🇸Metairie, Louisiana, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Cohen Children's Medical Center of New York
🇺🇸Lake Success, New York, United States
Cleveland Clinic Cystic Fibrosis Program
🇺🇸Cleveland, Ohio, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Hershey Medical Center Pennsylvania State University
🇺🇸Hershey, Pennsylvania, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
University of Texas Southwestern / Children's Health
🇺🇸Dallas, Texas, United States
University of California, San Francisco - Adult Center
🇺🇸San Francisco, California, United States
University of California, San Francisco - Peds Center
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
Primary Children's Cystic Fibrosis Center
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Froedtert & Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Tucson Cystic Fibrosis Center
🇺🇸Tucson, Arizona, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Rady Children's Hospital and Health Center at the University of California San Diego
🇺🇸San Diego, California, United States
CHOC Children's Hospital
🇺🇸Orange, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Wayne State University Harper University Hospital
🇺🇸Detroit, Michigan, United States
Children's Hospitals and Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Rutgers - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
The Minnesota Cystic Fibrosis Center
🇺🇸Minneapolis, Minnesota, United States
Columbia University Cystic Fibrosis Program
🇺🇸New York, New York, United States
University of Rochester Medical Center Strong Memorial
🇺🇸Rochester, New York, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
University of Texas Health Center at Tyler
🇺🇸Tyler, Texas, United States
West Virginia University - Morgantown
🇺🇸Morgantown, West Virginia, United States
Providence Medical Group, Cystic Fibrosis Center
🇺🇸Spokane, Washington, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Central Florida Pulmonary Group
🇺🇸Orlando, Florida, United States
The Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
University of Michigan, Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Kansas City
🇺🇸Kansas City, Missouri, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States