Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study (STOP360AG)

Chris Goss

Status and phase: Enrolling; Phase 4

Conditions: Cystic Fibrosis; Cystic Fibrosis Pulmonary Exacerbation

Treatments: Drug: Aminoglycoside; Drug: Beta-lactam antibiotic

Study type: Interventional

Funder types: Other

Identifiers

NCT05548283

STOP360-IP-22 AG

Details and patient eligibility

About

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?

Full 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.

Enrollment: 730 estimated patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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730 participants in 2 patient groups

β-lactam Only (Non-AG)

Other group

Description:

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.

Treatment:

Drug: Beta-lactam antibiotic

β-lactam and Aminoglycoside (AG)

Other group

Description:

Participants randomized to this arm will be prescribed a standard of care intravenous (IV) β-lactam and aminoglycoside selected by their treating physician.

Treatment:

Drug: Aminoglycoside

Drug: Beta-lactam antibiotic