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Cystic FibrosisSIMPLIFY-HSNCT06350461

Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study

A study testing Discontinuation of hypertonic saline (HS) and Continuation of hypertonic saline (HS) in people with Cystic Fibrosis, run by Nicole Hamblett at 81 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 cystic fibrosis (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
What is being tested?
Discontinuation of hypertonic saline (HS) and Continuation of hypertonic saline (HS)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
370 participants
Where
81 sitesUnited States
Study dates
25 Aug 2020to 11 Jul 2022
Phase
Interventional
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

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%) 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

81 sites in 1 country.

81 sites in 1 country

United States81 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, 30324

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Johns Hopkins University

    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

    Boston, Massachusetts, 02115

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27517

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia

    Charlottesville, Virginia, 22904

  • 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

  • Corewell Health Helen DeVos

    Grand Rapids, Michigan, 49546

  • 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

    Jacksonville, Florida, 32207

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Children's Mercy Kansas City

    Kansas City, Missouri, 64108

  • 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 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, 26506

  • 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

  • Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11042

  • Beth Israel Medical Center

    New York, New York, 10003

  • Lenox Hill Hospital Cystic Fibrosis Center

    New York, New York, 10028

  • 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 Clinic

    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

  • Atrium Health Wake Forest Baptist

    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 - Hypertonic Saline

Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating cystic fibrosis (CF), it is still largely unknown whether or not other chronic therapies can be safely stopped. This SIMPLIFY sub-study is being done to test whether or not it is safe to stop taking inhaled hypertonic saline in those people that are also taking elexacaftor/tezacaftor/ivacaftor (ETI).

ETI 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 ETI 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 (HS) also improves clearance of mucus from the lungs to support lung function and has been available to people with CF for many years. HS is considered to be relatively burdensome and it is not known whether HS can improve or maintain lung function above what is already gained through ETI use.

The goal of this SIMPLIFY sub-study is to get information about whether or not it is safe to stop hypertonic saline by testing if there is a change in lung function in participants with cystic fibrosis (CF) who are assigned to stop taking HS as compared to those who are assigned to keep taking HS while continuing to take ETI.

This is a sub study of master protocol SIMPLIFY-IP-19, NCT04378153.

The sub study investigating the impact of discontinuing and continuing dornase alfa is registered under NCTXXXXXXX (will add once available).

Read the detailed description

This SIMPLIFY sub-study (Hypertonic Saline (HS) Trial) is designed to evaluate the effects of discontinuing HS in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). This is an open label two-arm randomized non-inferiority trial consisting of a 2-week screening period, randomization to continue or discontinue hypertonic saline, followed by a 6-week study period. Participants at trial entry will be randomized 1:1 to either continue or discontinue their HS therapy.

Clinical outcomes (forced expiratory volume in 1 second [FEV1], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and patient reported outcomes to evaluate respiratory symptoms and the participant's perception of how stopping HS would impact their daily life will be evaluated in all subjects. Additionally, a subset of participants at selected study sites will participate in Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI).

Conditions
Cystic Fibrosis
Being tested
Discontinuation of hypertonic saline (HS), Continuation of hypertonic saline (HS)
Keywords
Cystic Fibrosis, CF, Withdrawal, ETI, hypertonic saline, discontinue
Medical subject headings
Cystic Fibrosis

What participants receive

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

  • Discontinuation of hypertonic saline (HS)Other

    Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.

  • Continuation of hypertonic saline (HS)Other

    Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.

Study groups in NCT06350461
Study groupRoleWhat they receive
HS-DiscontinueExperimentalDiscontinuation of current hypertonic saline (HS) therapy
Receives: Other: Discontinuation of hypertonic saline (HS)
HS-ContinueActive comparatorContinuation of current hypertonic saline (HS) therapy
Receives: Other: Continuation of hypertonic saline (HS)

What is being measured

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

  1. Absolute Change in FEV1 % Predicted From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

    Measured: Week 0 to Week 6

Secondary outcomes (11)

  1. Absolute Change in LCI 2.5 From Baseline to Week 6

    Difference between study arms (discontinue - continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Baseline (Week 0, if available, or else Week -2) to Week 6. LCI 2.5 is the number of times the volume in the lungs needs to turn over to expel an inert gas. A higher value of LCI 2.5 indicates poorer lung function.

    Measured: Baseline (Week 0 or Week -2) to Week 6

  2. Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary (CFRSD) asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms. Calculation of a score requires responses for at least 7 out of 8 symptoms.

    Measured: Week 0 to Week 6

  3. Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants 6 questions related to respiratory symptoms which are each assigned a score 1-4. The Respiratory Domain Scaled Score is calculated as follows: 100*[{sum of responses}/{number of responses}-1]/3 only if number of responses ≥ 3; otherwise the score is set to missing. The scaled score ranges from 0 to 100 where higher scores indicate improvement of symptoms.

    Measured: Week 0 to Week 6

  4. Absolute Change in FEV1 % Predicted From Week -2 to Week 0

    Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

    Measured: Week -2 to Week 0

  5. Absolute Change in FEV1 % Predicted From Week 0 to Week 2

    Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

    Measured: Week 0 to Week 2

  6. Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6. Includes antibiotics initiated for respiratory indications; excludes those taken as part of a chronic cycled regimen or for a UTI, skin infection, etc.

    Measured: Week 0 to Week 6

  7. Number and Percent of Participants Hospitalized From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the percent of subjects hospitalized from Week 0 to Week 6.

    Measured: Week 0 to Week 6

  8. Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6. Pulmonary exacerbations defined using Fuchs criteria.

    Measured: Week 0 to Week 6

  9. Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the percent of participants with at least one AE from Week 0 to Week 6. Includes serious and non-serious AEs.

    Measured: Week 0 to Week 6

  10. Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms

    Comparison of study arms (discontinue/continue) in the rate of AE occurrence (number of events divided by total follow-up weeks in each arm) from Week 0 to Week 6. Includes serious and non-serious AEs.

    Measured: Week 0 to Week 6

  11. Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6

    Difference between study arms (discontinue - continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6

    Measured: Week 0 to Week 6

Timeline

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

  1. First posted5 Apr 2024
  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
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
370 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06350461
Sponsor's protocol ID
SIMPLIFY-IP-19 HS
Acronym
SIMPLIFY-HS
Status last verified
May 2024
First submitted
1 Apr 2024
Last updated
1 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Discontinuation of hypertonic saline (HS) and Continuation of hypertonic saline (HS) in people with Cystic Fibrosis, run by Nicole Hamblett at 81 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 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 81 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 1 Oct 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?

Absolute Change in FEV1 % Predicted From Week 0 to Week 6 (time frame: Week 0 to Week 6). 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 NCT06350461.

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 1 Oct 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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