Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation

Intervention / Treatment
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* Drug: Beta-lactam antibiotic
* Drug: Aminoglycoside


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: β-lactam Only (Non-AG)<br>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. | Drug: Beta-lactam antibiotic<br>* Intravenous (IV) β-lactam will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).<br>* Other names: β-lactam;|
| Other: β-lactam and Aminoglycoside (AG)<br>Participants randomized to this arm will be prescribed a standard of care intravenous (IV) β-lactam and aminoglycoside selected by their treating physician. | Drug: Beta-lactam antibiotic<br>* Intravenous (IV) β-lactam will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).<br>* Other names: β-lactam;Drug: Aminoglycoside<br>* Intravenous (IV) aminoglycoside will be selected by the treating physician following standard of care. Treatment will last for 14 days (± 2 days).<br>* Other names: AG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, CF, Cystic Fibrosis Pulmonary Exacerbation, aminoglycoside, beta-lactam, β-lactam, STOP, STOP360