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Cystic FibrosisSIMPLIFYNCT04378153

Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy

An observational study of Cystic Fibrosis, run by Nicole Hamblett at 80 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Cystic Fibrosis
How many people
987 participants
Where
80 sitesUnited States
Study dates
25 Aug 2020to 11 Jul 2022
Phase
Observational
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: Participants with Cystic Fibrosis using either hypertonic saline or dornase alfa chronically (see eligibility criteria).

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

80 sites in 1 country.

80 sites in 1 country

United States80 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • University of Michigan, Michigan Medicine

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30327

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • John Hopkins Hospital

    Baltimore, Maryland, 21287

  • Billings Clinic

    Billings, Montana, 59101

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Saint Luke's Cystic Fibrosis Center of Idaho

    Boise, Idaho, 83702

  • Boston Children's Hospital, Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia

    Charlottesville, Virginia, 22903

  • Northwestern University

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

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

    Cleveland, Ohio, 44146

  • Cleveland Clinic Cystic Fibrosis Program

    Cleveland, Ohio, 44195

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Texas Southwestern / Children's Health

    Dallas, Texas, 75207

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • National Jewish Health

    Denver, Colorado, 80206

  • Wayne State University Harper University Hospital

    Detroit, Michigan, 48201

  • Monmouth Medical Center

    Eatontown, New Jersey, 07724

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32610

  • Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Hershey Medical Center Pennsylvania State University

    Hershey, Pennsylvania, 17033

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa

    Iowa City, Iowa, 52242

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Children's Mercy Kansas City

    Kansas City, Missouri, 64108

  • Cohen Children's Medical Center of New York

    Lake Success, New York, 11042

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40506

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • University of Louisville

    Louisville, Kentucky, 40202

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Tulane University

    Metairie, Louisiana, 70001

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Froedtert & Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • The Minnesota Cystic Fibrosis Center

    Minneapolis, Minnesota, 55455

  • West Virginia University - Morgantown

    Morgantown, West Virginia, 26507

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Rutgers - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

  • Yale University School of Medicine

    New Haven, Connecticut, 06520

  • Beth Israel Medical Center

    New York, New York, 10003

  • Columbia University Cystic Fibrosis Program

    New York, New York, 10032

  • CHOC Children's Hospital

    Orange, California, 92868

  • Central Florida Pulmonary Group

    Orlando, Florida, 32803

  • The Nemours Children's Clinic - Orlando

    Orlando, Florida, 32827

  • Stanford University Medical Center

    Palo Alto, California, 94304

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32514

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15224

  • Maine Medical Partners Pediatric Specialty Care

    Portland, Maine, 04102

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Virginia Commonwealth University

    Richmond, Virginia, 23219

  • University of Rochester Medical Center Strong Memorial

    Rochester, New York, 14642

  • Primary Children's Cystic Fibrosis Center

    Salt Lake City, Utah, 84113

  • Rady Children's Hospital and Health Center at the University of California San Diego

    San Diego, California, 92123

  • University of California, San Francisco - Adult Center

    San Francisco, California, 94143

  • University of California, San Francisco - Peds Center

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Providence Medical Group, Cystic Fibrosis Center

    Spokane, Washington, 99204

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Tampa General Hospital

    Tampa, Florida, 33606

  • Tucson Cystic Fibrosis Center

    Tucson, Arizona, 85724

  • University of Texas Health Center at Tyler

    Tyler, Texas, 75708

  • New York Medical College at Westchester Medical Center

    Valhalla, New York, 10595

  • Wake Forest University Baptist Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Master Protocol to Test the Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy (SIMPLIFY)

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.

Read more

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.

Read the detailed description

SIMPLIFY-IP-19 is a master protocol is designed to evaluate the independent effects of discontinuing hypertonic saline or dornase alfa in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). The hypertonic saline and dornase alfa sub studies are identical open label two-arm randomized non-inferiority trials consisting of a 2-week run-in period, randomization to continue or discontinue hypertonic saline or dornase alfa, 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 the hypertonic saline or dornase alfa 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.

This clinicalrials.gov registration, NCT04378153, summarizes the 2-week run-in and adherence period prior to participant enrollment in either the Hypertonic Saline or Dornase Alfa sub studies.

Two additional clincialtrials.gov records document the sub study specific enrollment and outcome measures.

Hypertonic Saline Study Record

  • NCT06350461
  • Brief Title: Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study (SIMPLIFY-HS)

Dornase Alfa Study Record

  • NCT06350474
  • Brief Title: Impact of Discontinuing Dornase Alfa in People With CF on Highly Effective CFTR Modulator Therapy-A SIMPLIFY Sub-Study (SIMPLIFY-DN)
Conditions
Cystic Fibrosis
Keywords
Cystic Fibrosis, CF, Withdrawal, Trikafta, hypertonic saline, dornase alfa, pulmozyme
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04378153
Study groupRoleWhat they receive
Master Study Run-inParticipants enrolled in the run-in phase of the master protocol.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2-week run-in period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2020
  2. Study start25 Aug 2020
  3. Primary completion11 Jul 2022
  4. Study completion11 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Prospective
Enrolment
987 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04378153
Sponsor's protocol ID
SIMPLIFY-IP-19
Acronym
SIMPLIFY
Status last verified
Nov 2024
First submitted
4 May 2020
Last updated
4 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38153868

  • Mayer-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.

    PubMed 36343646

  • Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.

    PubMed 33735508

  • Mayer-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.

    PubMed 33465316

Questions about this trial

What is this clinical trial studying?

An observational study of Cystic Fibrosis, run by Nicole Hamblett at 80 sites in United States.

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 6 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: finished, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States. 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?

Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Eligible to be Assessed for Sub-study Enrollment (time frame: 2-week run-in period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04378153, which also lists 4 linked publications.

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 4 Dec 2024.

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