Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation
Conditions
Keywords
Cystic Fibrosis, CF, Cystic Fibrosis Pulmonary Exacerbation, aminoglycoside, beta-lactam, β-lactam, STOP, STOP360
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.
Interventions
Intravenous (IV) β-lactam will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).
DRUGAminoglycoside
Intravenous (IV) aminoglycoside will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).
Sponsors
University of Washington
Medical University of South Carolina
Cystic Fibrosis Foundation
Chris Goss
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The aminoglycoside study will compare treatment of an IV β-lactam and aminoglycoside (AG) versus an IV β-lactam only (non-AG). Individuals will be randomly assigned in a 1:1 fashion to receive either the AG or non-AG intervention for a planned 14 day course of IV antibiotics. IV antibiotic treatments for each intervention arm will be selected by the treating physician following standard of care.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada, United States
Contacts
Primary ContactRachael Buckingham, BS
Backup ContactBarbra Fogarty
Outcome results
None listed