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

NCT06350461 | Completed Results DMC

• 1 other identifier: SIMPLIFY-IP-19 HS
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 81

Brief 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. 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. 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).

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; CF; Withdrawal; ETI; hypertonic saline; discontinue

Outcome Measures

Primary Outcomes (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.

  Week 0 to Week 6

Secondary Outcomes (11)

• Absolute Change in LCI 2.5 From Baseline to Week 6

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

• 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

  Week 0 to Week 6

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

  Week 0 to Week 6

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

  Week -2 to Week 0

• Absolute Change in FEV1 % Predicted From Week 0 to Week 2

  Week 0 to Week 2

Study Arms (2)

HS-Discontinue

EXPERIMENTAL

Discontinuation of current hypertonic saline (HS) therapy

Other: Discontinuation of hypertonic saline (HS)

HS-Continue

ACTIVE COMPARATOR

Continuation of current hypertonic saline (HS) therapy

Other: Continuation of hypertonic saline (HS)

Interventions

Discontinuation of hypertonic saline (HS) OTHER

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

HS-Discontinue

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%.

HS-Continue

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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%) 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.

Sponsors & Collaborators

• Nicole Hamblett: lead
• Cystic Fibrosis Foundation: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• University of Washington: collaborator

Study Sites (81)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Tucson Cystic Fibrosis Center

Tucson, Arizona, 85724, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

Location

CHOC Children's Hospital

Orange, California, 92868, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

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

San Diego, California, 92123, United States

Location

University of California, San Francisco - Adult Center

San Francisco, California, 94143, United States

Location

University of California, San Francisco - Peds Center

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Central Florida Pulmonary Group

Orlando, Florida, 32803, United States

Location

The Nemours Children's Clinic - Orlando

Orlando, Florida, 32827, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32514, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30324, United States

Location

Saint Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, 83702, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane University

Metairie, Louisiana, 70001, United States

Location

Maine Medical Partners Pediatric Specialty Care

Portland, Maine, 04102, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan, Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University Harper University Hospital

Detroit, Michigan, 48201, United States

Location

Corewell Health Helen DeVos

Grand Rapids, Michigan, 49546, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

The Minnesota Cystic Fibrosis Center

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Kansas City

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Monmouth Medical Center

Eatontown, New Jersey, 07724, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Cohen Children's Medical Center of New York

New Hyde Park, New York, 11042, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Lenox Hill Hospital Cystic Fibrosis Center

New York, New York, 10028, United States

Location

Columbia University Cystic Fibrosis Program

New York, New York, 10032, United States

Location

University of Rochester Medical Center Strong Memorial

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

New York Medical College at Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

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

Cleveland, Ohio, 44146, United States

Location

Cleveland Clinic Cystic Fibrosis Program

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Oregon Health & Sciences University

Portland, Oregon, 97239, United States

Location

Hershey Medical Center Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

University of Texas Southwestern / Children's Health

Dallas, Texas, 75207, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

University of Texas Health Center at Tyler

Tyler, Texas, 75708, United States

Location

Primary Children's Cystic Fibrosis Center

Salt Lake City, Utah, 84113, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Providence Medical Group, Cystic Fibrosis Clinic

Spokane, Washington, 99204, United States

Location

West Virginia University - Morgantown

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Margaret Kloster
• Organization: Seattle Children's

margaret.kloster@seattlechildrens.org

206-884-7862

Study Officials

• Nicole Mayer-Hamblett, PhD

  University of Washington/Seattle Children's

  PRINCIPAL INVESTIGATOR

• Alex Gifford, MD, FCCP

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• 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: April 1, 2024
• First Posted: April 5, 2024
• Study Start: August 25, 2020
• Primary Completion: July 11, 2022
• Study Completion: July 11, 2022
• Last Updated: October 1, 2024
• Results First Posted: October 1, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (81)