Cystic FibrosisPhase 4NCT02918409
IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy
A Phase 4 study testing Colistin and Tobramycin in people with Cystic Fibrosis, run by National Jewish Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Colistin and Tobramycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2016to 22 Nov 2021
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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. -
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Colistin, Tobramycin
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColistinDrug
TobramycinDrug
| Study group | Role | What they receive |
|---|---|---|
| Standard colistin arm | Active comparator | 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. Receives: Drug: Colistin |
| Modified colistin arm | Active comparator | 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). Receives: Drug: Colistin |
| Standard tobramycin arm | Active comparator | 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 Receives: Drug: Tobramycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change in Forced Expiratory Volume at One Second (FEV1) % Predicted Between Study Arms With Acute Pulmonary Exacerbation (APE) Treatment
absolute change in forced expiratory volume at one second (FEV1) % predicted, or percent predicted FEV1, between study arms with acute pulmonary exacerbation (APE) treatment
Measured: up to 14 days, from beginning to end of APE treatment
Rate of Occurrence of the Development of Acute Kidney Injury (AKI) During APE Treatment
Measured: up to 14 days, from beginning to end of APE treatment
Secondary outcomes (2)
Longitudinal Differences in Exacerbation Rates Between Tobramycin and Colistin Use as Seen in Readmission Rate
time to next hospital admission for pulmonary exacerbation measured in days when comparing of different antibiotic therapies
Measured: from the beginning of APE treatment to 12 months after APE treatment
Differences in Occurrences of Neurotoxicity and Ototoxicity Related Side Effects Between Study Arms as Reported by Treating Physician(s)
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.
Measured: up to 14 days, from beginning to end of APE treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2016 (estimated)
- Study start26 Aug 2016
- Primary completion10 Sep 2020
- Study completion22 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Jewish Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Milene Saavedra, MD, Principal investigator, National Jewish Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02918409
- Sponsor's protocol ID
- SAAVED15A0
- Status last verified
- Mar 2023
- First submitted
- 12 Apr 2016
- Last updated
- 28 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No