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)

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Discontinuation of hypertonic saline (HS); Other: Continuation of hypertonic saline (HS); Other: Discontinuation of dornase alfa (dnase); Other: Continuation of dornase alfa (dnase)

Detailed Description

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

Clinical outcomes (forced expiratory volume in 1 second [FEV1], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and the subject's perception of how stopping HS or dornase alfa (or both) would impact their daily life will be evaluated in all subjects. Additional outcome measurements will be conducted in a subset of subjects at selected study sites:

• Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI)
• Mucociliary Clearance (MCC) using inhaled radio-labeled particles to evaluate changes in mucociliary clearance

• Study Type: Interventional
• Enrollment (Actual): 870
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Tucson Cystic Fibrosis Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's and Women's Hospital Long Beach
    • Orange, California, United States, 92868
      • CHOC Children's Hospital
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • San Diego, California, United States, 92123
      • Rady Children's Hospital and Health Center at the University of California San Diego
    • San Francisco, California, United States, 94143
      • University of California, San Francisco - Adult Center
    • San Francisco, California, United States, 94158
      • University of California, San Francisco - Peds Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group
    • Orlando, Florida, United States, 32827
      • The Nemours Children's Clinic - Orlando
    • Pensacola, Florida, United States, 32514
      • Nemours Children's Clinic - Pensacola
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Emory University
  • Idaho
    • Boise, Idaho, United States, 83702
      • Saint Luke's Cystic Fibrosis Center of Idaho
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • Metairie, Louisiana, United States, 70001
      • Tulane University
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Partners Pediatric Specialty Care
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital, Brigham & Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan, Michigan Medicine
    • Detroit, Michigan, United States, 48201
      • Wayne State University Harper University Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • The Minnesota Cystic Fibrosis Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Monmouth Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers - Robert Wood Johnson Medical School
  • New York
    • Lake Success, New York, United States, 11042
      • Cohen Children's Medical Center of New York
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10032
      • Columbia University Cystic Fibrosis Program
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center Strong Memorial
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
    • Valhalla, New York, United States, 10595
      • New York Medical College at Westchester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44146
      • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Cystic Fibrosis Program
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Hershey Medical Center Pennsylvania State University
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Dallas, Texas, United States, 75207
      • University of Texas Southwestern / Children's Health
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Tyler, Texas, United States, 75708
      • University of Texas Health Center at Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Cystic Fibrosis Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Spokane, Washington, United States, 99204
      • Providence Medical Group, Cystic Fibrosis Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26507
      • West Virginia University - Morgantown
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%) 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HS-Discontinue (Study A); Discontinuation of current hypertonic saline (HS) therapy in Study A	Other: Discontinuation of hypertonic saline (HS); Discontinuation of current hypertonic saline (HS) therapy in Study A during 6-week study period.
Active Comparator: HS-Continue (Study A); Continuation of current hypertonic saline (HS) therapy in Study A	Other: Continuation of hypertonic saline (HS); Continuation of current hypertonic saline (HS) therapy in Study A 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%.
Experimental: Dnase-Discontinue (Study B); Discontinuation of current dornase alfa (dnase) therapy in Study B	Other: Discontinuation of dornase alfa (dnase); Discontinuation of current dornase alfa (dnase) therapy in Study B during 6-week study period.; Other Names: Discontinuation of pulmozyme
Active Comparator: Dnase-Continue (Study B); Continuation of current dornase alfa (dnase) therapy in Study B	Other: Continuation of dornase alfa (dnase); Continuation of current dornase alfa (dnase) therapy in Study B 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).; Other Names: Continuation of pulmozyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in FEV1 % predicted from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.	Week 0 to Week 6
Absolute change in FEV1 % predicted from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.	Week 0 to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the proportion of participants with at least one AE from Week 0 to Week 6.	Week 0 to Week 6
Incidence of Adverse Events (AEs) in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the proportion of participants with at least one AE from Week 0 to Week 6.	Week 0 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 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-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 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.	Week 0 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 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-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 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.	Week 0 to Week 6
Absolute change in LCI 2.5 from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Week 0 to Week 6.	Week 0 to Week 6
Absolute change in LCI 2.5 from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in LCI 2.5 (Lung Clearance Index) 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 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-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 from 3 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.	Week 0 to Week 6
Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-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 from 3 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.	Week 0 to Week 6
Absolute change in FEV1 % predicted from Week -2 to Week 0 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.	Week -2 to Week 0
Absolute change in FEV1 % predicted from Week -2 to Week 0 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the 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 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.	Week 0 to Week 2
Absolute change in FEV1 % predicted from Week 0 to Week 2 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.	Week 0 to Week 2
Initiation of acute antibiotics from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6	Week 0 to Week 6
Initiation of acute antibiotics from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6	Week 0 to Week 6
Hospitalizations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects hospitalized from Week 0 to Week 6	Week 0 to Week 6
Hospitalizations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects hospitalized from Week 0 to Week 6	Week 0 to Week 6
Pulmonary Exacerbations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6	Week 0 to Week 6
Pulmonary exacerbations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6	Week 0 to Week 6
Adverse events from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects experiencing an adverse event from Week 0 to Week 6	Week 0 to Week 6
Adverse events from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects experiencing an adverse event from Week 0 to Week 6	Week 0 to Week 6
Temporary or permanent changes from assigned therapy regimen due to adverse event from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms	Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6	Week 0 to Week 6
Temporary or permanent changes from assigned therapy regimen due to adverse event from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms	Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6	Week 0 to Week 6

Collaborators and Investigators

• Sponsor: Nicole Hamblett
• Collaborators: University of Washington; Dartmouth-Hitchcock Medical Center; Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Nicole Mayer-Hamblett, PhD, University of Washington/Seattle Children's; Principal Investigator: Alex Gifford, MD, FCCP, Dartmouth-Hitchcock Medical Center

Publications and helpful links

General Publications

• 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.
• 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. 2022 Nov 4:S2213-2600(22)00434-9. doi: 10.1016/S2213-2600(22)00434-9. Online ahead of print.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): July 11, 2022

Study Registration Dates

• First Submitted: May 4, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 10, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; hypertonic saline; Withdrawal; CF; Trikafta; dornase alfa; pulmozyme
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: SIMPLIFY-IP-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes