Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study

Cystic Fibrosis Clinical Trial

— STOP360AG  

Official title:

Standardizing Treatments for Pulmonary Exacerbations: A Platform for Evaluating Treatment Decisions to Improve Outcomes (STOP360) Aminoglycoside Study (AG Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05548283
• Other study ID #: STOP360-IP-22 AG
• Status: Recruiting
• Phase: Phase 4
• Start date: April 23, 2023
• Est. completion date: November 15, 2026

Study information

• Verified date: April 2024
• Source: Seattle Children's Hospital
• Contact: Rachael Buckingham, BS
• Phone: 206-884-7517
• Email: Rachael.buckingham[@]seattlechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

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 information / eligibility

• Status: Recruiting
• Enrollment: 730
• Est. completion date: November 15, 2026
• Est. primary completion date: November 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis Pulmonary Exacerbation
• Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Beta-lactam antibiotic
Intravenous (IV) ß-lactam will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).
• Aminoglycoside
Intravenous (IV) aminoglycoside will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).

Locations

Country	Name	City	State
Canada	University of Calgary Adult Cystic Fibrosis Clinic (Calgary, AB)	Calgary	Alberta
Canada	CF Centre Hospital for Sick Children (Toronto, ON)	Toronto	Ontario
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of Michigan, Michigan Medicine	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	John Hopkins Hospital	Baltimore	Maryland
United States	Billings Clinic	Billings	Montana
United States	The Children's Hospital Alabama, University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Luke's Cystic Fibrosis Center of Idaho	Boise	Idaho
United States	Boston Children's Hospital, Brigham & Women's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati 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	University of Texas Southwestern	Dallas	Texas
United States	University of Texas Southwestern / Children's Health	Dallas	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego	La Jolla	California
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Miami	Miami	Florida
United States	West Virginia University - Morgantown	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Rutgers - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Children's Hospital of New York	New York	New York
United States	Lenox Hill Hospital Cystic Fibrosis Center	New York	New York
United States	Oklahoma Cystic Fibrosis Center	Oklahoma City	Oklahoma
United States	CHOC Children's Hospital	Orange	California
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health Sciences University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California at Davis Medical Center	Sacramento	California
United States	SSM Health Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Providence Medical Group, Cystic Fibrosis Clinic	Spokane	Washington
United States	Toledo Children's Hospital	Toledo	Ohio
United States	Tucson Cystic Fibrosis Center	Tucson	Arizona
United States	New York Medical College at Westchester Medical Center	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	University of Massachusetts Memorial Health Care	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Chris Goss	Cystic Fibrosis Foundation, Medical University of South Carolina, University of Washington

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change in FEV1 % Predicted at Week 4 in Aminoglycoside (AG) Study	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)	Four weeks
Primary	Incidence of Adverse Events (AEs) in Aminoglycoside (AG) Study Intervention Arms	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).	Six Weeks
Secondary	Absolute Change in CFRSD-CRISS Score at Week 4 in Aminoglycoside (AG) Study	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.	Four weeks