Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study
- Conditions
- Cystic FibrosisCystic Fibrosis Pulmonary Exacerbation
- Interventions
- Drug: Beta-lactam antibioticDrug: Aminoglycoside
- Registration Number
- NCT05548283
- Lead Sponsor
- Chris Goss
- Brief Summary
The purpose of this study is to look at pulmonary exacerbations in people with cystic fibrosis (CF) that need to be treated with antibiotics given through a tube inserted into a vein (intravenous or IV). A pulmonary exacerbation is a worsening of respiratory symptoms in people with CF that needs medical intervention. Both doctors and CF patients are trying to understand the best way to treat pulmonary exacerbations. This study is trying to answer the following questions about treating a pulmonary exacerbation:
* Do participants have the same improvement in lung function and symptoms if they are treated with one type of antibiotic (called beta-lactams or β-lactams) versus taking two different types of antibiotics (tobramycin and β-lactams)?
* Is taking one type of antibiotic just as good as taking two types?
- Detailed Description
Cystic Fibrosis Foundation (CFF) treatment guidelines for the management of pulmonary exacerbations (PEx) identified evidence gaps in current clinical best practices. The STOP program offers a platform for the conduct of controlled trials to develop the evidence base in order to define clinical best practices. The interventional Aminoglycoside Study (AG Study) will be a prospective, multi-center, parallel group, randomized (1:1 ratio), open-label, superiority study of intravenous aminoglycoside and β-lactams versus intravenous β-lactams only. Randomization will occur at Visit 1. The primary objective of this platform trial is to evaluate the efficacy and safety of differing treatments in CF PEx during a planned 14 day course of IV antimicrobials. Primary efficacy will be evaluated as the difference in mean Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) changes from Visit 1 to Visit 2 (Day 28 ± 2 days) between intervention arms.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 730
- All genders ≥ 6 years of age at Visit 1
- Documentation of a CF diagnosis
- Clinician intent to treat index CF PEx with a planned 14-day course of IV antimicrobials
- At least one documented Pa positive culture within two years prior to Visit 1
- Participant is not pregnant
- No known renal impairment or history of solid organ transplantation
- No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6 weeks prior to Visit 1
- No use of investigational therapies, new CF transmembrane conductance regulator (CFTR) modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to Visit 1
- No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
- No more than one day of IV aminoglycosides administered for the current PEx treatment prior to Visit 1
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description β-lactam Only (Non-AG) Beta-lactam antibiotic Participants randomized to this arm will be prescribed a standard of care intravenous (IV) β-lactam as selected by their treating physician. Treatment must not include an IV aminoglycoside. β-lactam and Aminoglycoside (AG) Beta-lactam antibiotic Participants randomized to this arm will be prescribed a standard of care intravenous (IV) β-lactam and aminoglycoside selected by their treating physician. β-lactam and Aminoglycoside (AG) Aminoglycoside Participants randomized to this arm will be prescribed a standard of care intravenous (IV) β-lactam and aminoglycoside selected by their treating physician.
- Primary Outcome Measures
Name Time Method Absolute Change in FEV1 % Predicted at Week 4 in Aminoglycoside (AG) Study Four weeks Difference between aminoglycoside (AG) study intervention arms (AG - Non-AG) in the absolute change in FEV1 % predicted from Week 0 (Day 0) to Week 4 (Day 28 ± 2 days)
Incidence of Adverse Events (AEs) in Aminoglycoside (AG) Study Intervention Arms Six Weeks Difference between aminoglycoside (AG) study intervention arms (AG - Non-AG) in the proportion of participants with at least one AE from Week 0 (Day 0) to Week 6 (Day 44 ± 2 days).
- Secondary Outcome Measures
Name Time Method Absolute Change in CFRSD-CRISS Score at Week 4 in Aminoglycoside (AG) Study Four weeks Difference between aminoglycoside (AG) study intervention arms (AG - Non-AG) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) from Week 0 (Day 0) to Week 4 (Day 28 ± 2 days). The CFRSD-CRISS is derived from a set of questions asking 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.
Trial Locations
- Locations (60)
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Tucson Cystic Fibrosis Center
🇺🇸Tucson, Arizona, United States
CHOC Children's Hospital
🇺🇸Orange, California, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Boston Children's Hospital, Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
University of Massachusetts Memorial Health Care
🇺🇸Worcester, Massachusetts, United States
SSM Health Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Lenox Hill Hospital Cystic Fibrosis Center
🇺🇸New York, New York, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Children's Hospital of New York
🇺🇸New York, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
University of Texas Southwestern / Children's Health
🇺🇸Dallas, Texas, United States
Providence Medical Group, Cystic Fibrosis Clinic
🇺🇸Spokane, Washington, United States
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
University of Calgary Adult Cystic Fibrosis Clinic (Calgary, AB)
🇨🇦Calgary, Alberta, Canada
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Saint Luke's Cystic Fibrosis Center of Idaho
🇺🇸Boise, Idaho, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Rutgers - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of California San Diego
🇺🇸La Jolla, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
West Virginia University - Morgantown
🇺🇸Morgantown, West Virginia, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Oklahoma Cystic Fibrosis Center
🇺🇸Oklahoma City, Oklahoma, United States
The Children's Hospital Alabama, University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
New York Medical College at Westchester Medical Center
🇺🇸Valhalla, New York, United States
University of California at Davis Medical Center
🇺🇸Sacramento, California, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
University of Michigan, Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States