IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis
Intervention: Colistin; Tobramycin
Intervention MeSH terms: Tobramycin; Colistin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to find the safest and most effective way to administer IV
      antibiotics to treat acute pulmonary exacerbations (APEs) in patients with cystic fibrosis
      (CF) that are caused by pathogens, like Pseudomonas aeruginosa. This study will test the
      safety and effectiveness of two commonly prescribed IV antibiotics: tobramycin and colistin.
      Though regularly used, not much is known about how these drugs compare with each other in
      terms of their toxicities, both during short term treatment of an APE and after many
      treatment courses with these drugs over many years. There are currently no guidelines on the
      safest and most effective antibiotics to use when treating APEs. We will study kidney
      function, sputum cultures, and treatment outcomes in patients receiving routine
      administration of one of these two IV antibiotics. We will also test these outcomes in
      patients receiving a less frequent dosing schedule for IV colistin. The hope is that this new
      schedule for IV colistin, which is twice a day and adjusted based on blood and urine tests,
      will reduce harmful side effects, such as kidney damage, while still being a powerful
      treatment against CF microbial pathogens.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female ≥ 18 years of age at Visit 1.

          2. Documentation of CF diagnosis as evidenced by one or more clinical features consistent
             with the CF phenotype and one or more of the following criteria:

               -  Sweat chloride equal or greater than 60 mEq/L by quantitative pilocarpine
                  iontophoresis test.

               -  Two well-characterized mutations in the cystic fibrosis transmembrane conductance
                  regulator (CFTR) gene

               -  Abnormal nasal potential difference (NPD) as measured by a change in NPD in
                  response to a low chloride solution and isoproterenol of less than -5 mV.

          3. Documentation of the presence of an acute pulmonary exacerbation, based on CF
             Foundation guidelines, as diagnosed by a faculty member of the Denver Adult CF
             Program.

          4. Respiratory culture(s) demonstrating evidence of Pseudomonas aeruginosa or
             Achromobacter species airway infection.

          5. Subject is able to produce sputum, undergo phlebotomy, and provide written consent.

          6. The subject's treating physician has determined that they should receive either
             tobramycin or colistin intravenously as one of the designated agents for their APE
             treatment. Subjects who are able to receive either tobramycin or colistin as part of
             their antibiotic regimen will be randomized into one of three arms. If a treating
             physician deems that a subject cannot receive tobramycin due to vestibular toxicity,
             ototoxicity or bacterial resistance, the subject will be randomized to either standard
             or PK-adjusted colistin.

        Exclusion Criteria:

          1. Concomitant administration of bactrim (due to effects on creatinine).

          2. Concomitant administration of inhaled colistin for patients in the colistin PK arm, as
             this will create inaccuracies in colistin sputum concentration measurements.

          3. Patients being treated for B. cepacia, due to colistin resistance by the pathogen.

          4. Presence of chronic renal insufficiency, with abnormal baseline creatinine >1.2mg/dL.

          5. Presence of a condition or abnormality that in the opinion of the investigator would
             compromise the safety of the patient or the quality of the data.

          6. Inability to perform reproducible spirometry.

          7. Inability to expectorate sputum. -