IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy

NCT ID: NCT02918409

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-26
• Study Completion Date: 2021-11-22

Brief 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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard colistin arm

Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.

Group Type: ACTIVE_COMPARATOR

Colistin

Intervention Type: DRUG

Modified colistin arm

Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).

Group Type: ACTIVE_COMPARATOR

Colistin

Intervention Type: DRUG

Standard tobramycin arm

Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes

Group Type: ACTIVE_COMPARATOR

Tobramycin

Intervention Type: DRUG

Interventions

Colistin

Intervention Type: DRUG

Tobramycin

Intervention Type: DRUG

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. -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Jewish Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Milene Saavedra, MD

Role: PRINCIPAL_INVESTIGATOR

National Jewish Health

Locations

National Jewish Health

Denver, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

SAAVED15A0

Identifier Type: -

Identifier Source: org_study_id