- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02918409
IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy
March 28, 2023 updated by: National Jewish Health
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
51
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Colorado
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Denver, Colorado, United States, 80206
- National Jewish Health
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Male or female ≥ 18 years of age at Visit 1.
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.
- 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.
- Respiratory culture(s) demonstrating evidence of Pseudomonas aeruginosa or Achromobacter species airway infection.
- Subject is able to produce sputum, undergo phlebotomy, and provide written consent.
- 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:
- Concomitant administration of bactrim (due to effects on creatinine).
- Concomitant administration of inhaled colistin for patients in the colistin PK arm, as this will create inaccuracies in colistin sputum concentration measurements.
- Patients being treated for B. cepacia, due to colistin resistance by the pathogen.
- Presence of chronic renal insufficiency, with abnormal baseline creatinine >1.2mg/dL.
- 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.
- Inability to perform reproducible spirometry.
- Inability to expectorate sputum. -
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: 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.
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Active Comparator: 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).
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Active Comparator: 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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute Change in Forced Expiratory Volume at One Second (FEV1) % Predicted Between Study Arms With Acute Pulmonary Exacerbation (APE) Treatment
Time Frame: up to 14 days, from beginning to end of APE treatment
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absolute change in forced expiratory volume at one second (FEV1) % predicted, or percent predicted FEV1, between study arms with acute pulmonary exacerbation (APE) treatment
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up to 14 days, from beginning to end of APE treatment
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Rate of Occurrence of the Development of Acute Kidney Injury (AKI) During APE Treatment
Time Frame: up to 14 days, from beginning to end of APE treatment
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up to 14 days, from beginning to end of APE treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Achievement of Steady State With Pharmacokinetic (PK)-Adjusted Colistin Therapy
Time Frame: up to 14 days, from beginning to end of APE treatment
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up to 14 days, from beginning to end of APE treatment
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Longitudinal Differences in Exacerbation Rates Between Tobramycin and Colistin Use as Seen in Readmission Rate
Time Frame: from the beginning of APE treatment to 12 months after APE treatment
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time to next admission for exacerbation measured in days when comparing of different antibiotic therapies
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from the beginning of APE treatment to 12 months after APE treatment
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Differences in Occurrences of Neurotoxicity and Ototoxicity Related Side Effects Between Study Arms as Reported by Treating Physician(s)
Time Frame: up to 14 days, from beginning to end of APE treatment
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absolute occurrences of adverse event rates are being compared between treatment groups using logistic regression, adjusting for age, co-administration of medications such as vancomycin and trimethoprim-sulfamethoxazole, baseline FEV1, admits in the previous year, and diagnosis of CF related diabetes (CFRD) as covariates.
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up to 14 days, from beginning to end of APE treatment
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Measurement of Pharmacokinetics of Colistin's Active Metabolites in a Broad CF Population Through Peak, Trough, and Midpoint Blood Draws
Time Frame: up to 14 days, from beginning to end of APE treatment
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up to 14 days, from beginning to end of APE treatment
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Comparison of Plasma Pharmacokinetics of Colistin's Active Metabolites With Levels Achieved in the Sputum, in Order to Calculate Epithelial Lining Fluid Concentrations, Through Mass Spectrometry
Time Frame: up to 14 days, from beginning to end of APE treatment
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up to 14 days, from beginning to end of APE treatment
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Novel Biomarkers of Nephrotoxic AKI, Prior to Serum Creatinine Increases, Based on Urine Protein:Creatinine Ratios
Time Frame: up to 14 days, from beginning to end of APE treatment
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up to 14 days, from beginning to end of APE treatment
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Novel Biomarkers of Nephrotoxic AKI, Prior to Serum Creatinine Increases, Based on the Urine Biomarker Nephrocheck® Point-of-care Assay
Time Frame: up to 14 days, from beginning to end of APE treatment
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up to 14 days, from beginning to end of APE treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 26, 2016
Primary Completion (Actual)
September 10, 2020
Study Completion (Actual)
November 22, 2021
Study Registration Dates
First Submitted
April 12, 2016
First Submitted That Met QC Criteria
September 26, 2016
First Posted (Estimate)
September 29, 2016
Study Record Updates
Last Update Posted (Actual)
April 21, 2023
Last Update Submitted That Met QC Criteria
March 28, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SAAVED15A0
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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