Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy
SIMPLIFY
A Master Protocol to Test the Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy (SIMPLIFY)
1 other identifier
observational
987
1 country
80
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Aug 2020
80 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 4, 2020
CompletedFirst Posted
Study publicly available on registry
May 7, 2020
CompletedStudy Start
First participant enrolled
August 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 11, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 11, 2022
CompletedResults Posted
Study results publicly available
September 23, 2024
CompletedDecember 4, 2024
November 1, 2024
1.9 years
May 4, 2020
July 6, 2023
November 15, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Eligible to be Assessed for Sub-study Enrollment
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.
2-week run-in period
Study Arms (1)
Master Study Run-in
Participants enrolled in the run-in phase of the master protocol.
Eligibility Criteria
Participants with Cystic Fibrosis using either hypertonic saline or dornase alfa chronically (see eligibility criteria).
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Nicole Hamblettlead
- Cystic Fibrosis Foundationcollaborator
- Dartmouth-Hitchcock Medical Centercollaborator
- University of Washingtoncollaborator
Study Sites (80)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Providence Alaska Medical Center
Anchorage, Alaska, 99508, United States
Tucson Cystic Fibrosis Center
Tucson, Arizona, 85724, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
CHOC Children's Hospital
Orange, California, 92868, United States
Stanford University Medical Center
Palo Alto, California, 94304, United States
Rady Children's Hospital and Health Center at the University of California San Diego
San Diego, California, 92123, United States
University of California, San Francisco - Adult Center
San Francisco, California, 94143, United States
University of California, San Francisco - Peds Center
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
National Jewish Health
Denver, Colorado, 80206, United States
Yale University School of Medicine
New Haven, Connecticut, 06520, United States
University of Florida
Gainesville, Florida, 32610, United States
Nemours Children's Clinic
Jacksonville, Florida, 32207, United States
Central Florida Pulmonary Group
Orlando, Florida, 32803, United States
The Nemours Children's Clinic - Orlando
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32514, United States
All Children's Hospital
St. Petersburg, Florida, 33701, United States
Tampa General Hospital
Tampa, Florida, 33606, United States
Emory University
Atlanta, Georgia, 30327, United States
Saint Luke's Cystic Fibrosis Center of Idaho
Boise, Idaho, 83702, United States
Northwestern University
Chicago, Illinois, 60611, United States
OSF Saint Francis Medical Center
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Iowa
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40506, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Tulane University
Metairie, Louisiana, 70001, United States
Maine Medical Partners Pediatric Specialty Care
Portland, Maine, 04102, United States
John Hopkins Hospital
Baltimore, Maryland, 21287, United States
Boston Children's Hospital, Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
University of Michigan, Michigan Medicine
Ann Arbor, Michigan, 48109, United States
Wayne State University Harper University Hospital
Detroit, Michigan, 48201, United States
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404, United States
The Minnesota Cystic Fibrosis Center
Minneapolis, Minnesota, 55455, United States
Children's Mercy Kansas City
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Billings Clinic
Billings, Montana, 59101, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Monmouth Medical Center
Eatontown, New Jersey, 07724, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Rutgers - Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08903, United States
Cohen Children's Medical Center of New York
Lake Success, New York, 11042, United States
Beth Israel Medical Center
New York, New York, 10003, United States
Columbia University Cystic Fibrosis Program
New York, New York, 10032, United States
University of Rochester Medical Center Strong Memorial
Rochester, New York, 14642, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
New York Medical College at Westchester Medical Center
Valhalla, New York, 10595, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44146, United States
Cleveland Clinic Cystic Fibrosis Program
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
Oregon Health Sciences University
Portland, Oregon, 97239, United States
Hershey Medical Center Pennsylvania State University
Hershey, Pennsylvania, 17033, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
University of Texas Southwestern / Children's Health
Dallas, Texas, 75207, United States
University of Texas Southwestern
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
University of Texas Health Center at Tyler
Tyler, Texas, 75708, United States
Primary Children's Cystic Fibrosis Center
Salt Lake City, Utah, 84113, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
University of Virginia
Charlottesville, Virginia, 22903, United States
Virginia Commonwealth University
Richmond, Virginia, 23219, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Providence Medical Group, Cystic Fibrosis Center
Spokane, Washington, 99204, United States
West Virginia University - Morgantown
Morgantown, West Virginia, 26507, United States
University of Wisconsin
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (4)
Gold LS, Hansen RN, Mayer-Hamblett N, Nichols DP, Gifford AH, Kloster M, Goss CH, Kessler L. The cost of simplifying treatments for cystic fibrosis: Implications of the SIMPLIFY trial. J Manag Care Spec Pharm. 2024 Jan;30(1):26-33. doi: 10.18553/jmcp.2024.30.1.26.
PMID: 38153868DERIVEDMayer-Hamblett N, Ratjen F, Russell R, Donaldson SH, Riekert KA, Sawicki GS, Odem-Davis K, Young JK, Rosenbluth D, Taylor-Cousar JL, Goss CH, Retsch-Bogart G, Clancy JP, Genatossio A, O'Sullivan BP, Berlinski A, Millard SL, Omlor G, Wyatt CA, Moffett K, Nichols DP, Gifford AH; SIMPLIFY Study Group. Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials. Lancet Respir Med. 2023 Apr;11(4):329-340. doi: 10.1016/S2213-2600(22)00434-9. Epub 2022 Nov 4.
PMID: 36343646DERIVEDYang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.
PMID: 33735508DERIVEDMayer-Hamblett N, Nichols DP, Odem-Davis K, Riekert KA, Sawicki GS, Donaldson SH, Ratjen F, Konstan MW, Simon N, Rosenbluth DB, Retsch-Bogart G, Clancy JP, VanDalfsen JM, Buckingham R, Gifford AH. Evaluating the Impact of Stopping Chronic Therapies after Modulator Drug Therapy in Cystic Fibrosis: The SIMPLIFY Clinical Trial Study Design. Ann Am Thorac Soc. 2021 Aug;18(8):1397-1405. doi: 10.1513/AnnalsATS.202010-1336SD.
PMID: 33465316DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Adverse events were not collected as part of the run-in phase of the study.
Results Point of Contact
- Title
- Margaret Kloster
- Organization
- Seattle Children's
Study Officials
- PRINCIPAL INVESTIGATOR
Nicole Mayer-Hamblett, PhD
University of Washington/Seattle Children's
- PRINCIPAL INVESTIGATOR
Alex Gifford, MD, FCCP
Dartmouth-Hitchcock Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine Adjunct Professor, Biostatistics, University of Washington School of Medicine Co-Executive Director, Cystic Fibrosis Therapeutics Development
Study Record Dates
First Submitted
May 4, 2020
First Posted
May 7, 2020
Study Start
August 25, 2020
Primary Completion
July 11, 2022
Study Completion
July 11, 2022
Last Updated
December 4, 2024
Results First Posted
September 23, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will not share