Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study

Phase 4

Recruiting

• Conditions: Cystic Fibrosis; Cystic Fibrosis Pulmonary Exacerbation
• Interventions: Drug: Beta-lactam antibiotic; Drug: 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.

Study Timeline

• Study First Submitted: 2022-09-16
• Study First Submitted QC: 2022-09-16
• Study First Posted: 2022-09-21
• Study Start: 2023-04-23
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-23
• Last Update Posted: 2024-08-26
• Primary Completion: 2026-11-15
• Study Completion: 2026-11-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 730

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

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)

The Children's Hospital Alabama, University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Tucson Cystic Fibrosis Center; 🇺🇸 Tucson, Arizona, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Long Beach Memorial Medical Center; 🇺🇸 Long Beach, California, United States

CHOC Children's Hospital; 🇺🇸 Orange, California, United States

University of California at Davis Medical Center; 🇺🇸 Sacramento, California, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Joe DiMaggio Children's Hospital; 🇺🇸 Hollywood, Florida, United States

Nemours Children's Clinic; 🇺🇸 Jacksonville, Florida, United States

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