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

NCT ID: NCT06350461

Last Updated: 2024-10-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-25

Study Completion Date

2022-07-11

Brief Summary

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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).

Detailed Description

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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

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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HS-Discontinue

Discontinuation of current hypertonic saline (HS) therapy

Group Type EXPERIMENTAL

Discontinuation of hypertonic saline (HS)

Intervention Type OTHER

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

HS-Continue

Continuation of current hypertonic saline (HS) therapy

Group Type ACTIVE_COMPARATOR

Continuation of hypertonic saline (HS)

Intervention Type 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%.

Interventions

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Discontinuation of hypertonic saline (HS)

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

Intervention Type OTHER

Continuation of hypertonic saline (HS)

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%.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cystic Fibrosis Foundation

OTHER

Sponsor Role collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

Nicole Hamblett

OTHER

Sponsor Role lead

Responsible Party

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Nicole Hamblett

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

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Nicole Mayer-Hamblett, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington/Seattle Children's

Alex Gifford, MD, FCCP

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

Tucson Cystic Fibrosis Center

Tucson, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

CHOC Children's Hospital

Orange, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

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

San Diego, California, United States

Site Status

University of California, San Francisco - Adult Center

San Francisco, California, United States

Site Status

University of California, San Francisco - Peds Center

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Central Florida Pulmonary Group

Orlando, Florida, United States

Site Status

The Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Saint Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Tulane University

Metairie, Louisiana, United States

Site Status

Maine Medical Partners Pediatric Specialty Care

Portland, Maine, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan, Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

Wayne State University Harper University Hospital

Detroit, Michigan, United States

Site Status

Corewell Health Helen DeVos

Grand Rapids, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States

Site Status

The Minnesota Cystic Fibrosis Center

Minneapolis, Minnesota, United States

Site Status

Children's Mercy Kansas City

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Monmouth Medical Center

Eatontown, New Jersey, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

Lenox Hill Hospital Cystic Fibrosis Center

New York, New York, United States

Site Status

Columbia University Cystic Fibrosis Program

New York, New York, United States

Site Status

University of Rochester Medical Center Strong Memorial

Rochester, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

New York Medical College at Westchester Medical Center

Valhalla, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

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

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Cystic Fibrosis Program

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

Oregon Health & Sciences University

Portland, Oregon, United States

Site Status

Hershey Medical Center Pennsylvania State University

Hershey, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

University of Texas Southwestern / Children's Health

Dallas, Texas, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

University of Texas Health Center at Tyler

Tyler, Texas, United States

Site Status

Primary Children's Cystic Fibrosis Center

Salt Lake City, Utah, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Providence Medical Group, Cystic Fibrosis Clinic

Spokane, Washington, United States

Site Status

West Virginia University - Morgantown

Morgantown, West Virginia, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Children's Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SIMPLIFY-IP-19 HS

Identifier Type: -

Identifier Source: org_study_id

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