Cystic FibrosisNCT04335370
Pharmacokinetics of Polymyxin B in Adult Patients With Cystic Fibrosis
An observational study of Cystic Fibrosis and Polymyxin B, run by University of Michigan at 1 site in United States.
Trial summary
Cystic fibrosis (CF) pulmonary disease is a major cause of morbidity and mortality in CF patients and is punctuated by episodes of acute exacerbation that require antibiotic treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis, Polymyxin B
- What is being tested?
- Blood Draw
- Type of treatment
- Injection or infusion
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jan 2019to 1 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: CF patients admitted to the University of Michigan hospitals requiring polymyxin B as part of clinical care
Who may be able to join
- Adults ≥ 18 years of age.
- Diagnosis of CF.
- Receiving polymyxin B in the course of routine care.
Who cannot join
- Evidence of acute kidney injury during the 48 hours prior to and following initiation of PMB therapy.
- Extracorporeal organ support (including ECMO, iHD, and CRRT).
- Pregnant or breastfeeding women.
Trial locations and contacts
1 site in 1 country.
About this study
Cystic fibrosis (CF) pulmonary disease is a major cause of morbidity and mortality in CF patients and is punctuated by episodes of acute exacerbation that require antibiotic treatment. Pseudomonas aeruginosa is the predominant bacterial pathogen isolated in patients with acute exacerbations, and practice guidelines recommend combination antibiotics directed against this pathogen as initial therapy. Such therapy traditionally consists of an antipseudomonal beta-lactam with either an antipseudomonal fluoroquinolone or an aminoglycoside. With growing P. aeruginosa multi-drug resistance, more adult patients present with isolates resistant to these traditional options.
The polymyxins are a class of cyclic peptide antibiotics that exert bactericidal activity through binding to the lipopolysaccharide component of gram-negative bacterial membranes and include colistin and polymyxin B (PMB). In recent years, there is growing evidence of increased rates of acute kidney injury associated with colistin in critically ill patients. Additionally, population pharmacokinetic (PK) studies suggest that fixed drug dosing may yield an improved therapeutic index over the traditional weight-based dosing of this agent. Thus there is growing interest in use of PMB as an alternative in CF acute exacerbations but the optimal dosage regimen is not known.
This is a single-center, open-label, non-interventional study to characterize the pharmacokinetics and safety of fixed-dose PMB in adult patients with CF by measuring serum concentrations in patients receiving IV therapy as a part of routine care. This study will help to validate existing population PK models and allow for adjustment of patient specific covariates (i.e. weight, renal function) unique to adult patients with CF. The study will also monitor for nephrotoxicity and neurotoxicity to determine if PMB has an acceptable margin of safety in this patient population. This investigation is the first to prospectively validate the pharmacokinetics and toxicities of fixed-dose PMB in CF and will guide optimal use of this compound in the management of acute pulmonary exacerbations.
Read the detailed description
This study initially planned to include "Change in forced expiratory volume in one second (FEV1)" and "Non-response to therapy" as secondary outcome measures. These outcome measures were removed, as the small number of participants prohibited collection of significant data beyond what was collected for the baseline measures.
- Conditions
- Cystic Fibrosis, Polymyxin B
- Being tested
- Blood Draw
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood DrawOther
Blood samples will be collected from enrolled patients at 5 time points during a single dosing interval:
- Prior to start of infusion
- End of infusion
- One hour after end of infusion
- Three hours after end of infusion
- Eight hours after start of infusion
| Study group | Role | What they receive |
|---|---|---|
| Patients with CF lung disease receiving Polymyxin B (PMB) | Participants receiving polymyxcin B as part of standard of care treatment for CF exacerbation will have blood drawn measure blood concentrations of PMB Receives: Other: Blood Draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Polymyxin B compartmental population pharmacokinetics model
The population pharmacokinetics of polymyxin B will be modeled based on the observed polymyxin B1 and B2 concentrations in plasma from enrolled patients who receive at least 1 dose of polymyxin B
Measured: From immediately prior to a dose of therapy through 8 hours after therapy, approximately 8 hours
Secondary outcomes (4)
Acute kidney injury
Frequency of acute kidney injury occurring between 48 hours after initiation of polymyxin B and 48 hours after end of therapy
Measured: From 48 hours after first dose through 48 hours after end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
Neurotoxicity
Frequency of neurotoxicities occurring during polymyxin B treatment as documented by the primary clinical team
Measured: From initiation of first dose through end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
Change in forced expiratory volume in one second (FEV1)
After completion of polymyxin B therapy as documented by the primary clinical team
Measured: FEV1 at baseline to 7 days post treatment, approximately 14-90 days in total
Non-reponse to therapy
Proportion of subjects requiring a change to antibiotic therapy due to non-response as documented by the primary clinical team
Measured: From initiation of therapy through end of therapy, approximately 7-21 days depending on prescribed length of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start9 Jan 2019
- Primary completion1 Jul 2021
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Principal investigator, Shijing Jia, University of Michigan
- Investigators
- Shijing Jia, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04335370
- Sponsor's protocol ID
- HUM00150013
- Status last verified
- Jul 2023
- First submitted
- 2 Apr 2020
- Last updated
- 25 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Crass RL, Al Naimi T, Wen B, Souza E, Murray S, Pai MP, Jia S. Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0079221. doi: 10.1128/AAC.00792-21. Epub 2021 Jul 12.
PubMed 34252297
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Polymyxin B in Adult Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT04335370
- Acronym / sponsor ID
- HUM00150013
- Conditions
- Cystic Fibrosis, Polymyxin B
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- 9 Jan 2019 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 6 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cystic fibrosis (CF) pulmonary disease is a major cause of morbidity and mortality in CF patients and is punctuated by episodes of acute exacerbation that require antibiotic treatment. Pseudomonas aeruginosa is the predominant bacterial pathogen isolated in patients with acute exacerbations, and practice guidelines recommend combination antibiotics directed against this pathogen as initial therapy. Such therapy traditionally consists of an antipseudomonal beta-lactam with either an antipseudomonal fluoroquinolone or an aminoglycoside. With growing P. aeruginosa multi-drug resistance, more adult patients present with isolates resistant to these traditional options.
The polymyxins are a class of cyclic peptide antibiotics that exert bactericidal activity through binding to the lipopolysaccharide component of gram-negative bacterial membranes and include colistin and polymyxin B (PMB). In recent years, there is growing evidence of increased rates of acute kidney injury associated with colistin in critically ill patients. Additionally, population pharmacokinetic (PK) studies suggest that fixed drug dosing may yield an improved therapeutic index over the traditional weight-based dosing of this agent. Thus there is growing interest in use of PMB as an alternative in CF acute exacerbations but the optimal dosage regimen is not known.
This is a single-center, open-label, non-interventional study to characterize the pharmacokinetics and safety of fixed-dose PMB in adult patients with CF by measuring serum concentrations in patients receiving IV therapy as a part of routine care. This study will help to validate existing population PK models and allow for adjustment of patient specific covariates (i.e. weight, renal function) unique to adult patients with CF. The study will also monitor for nephrotoxicity and neurotoxicity to determine if PMB has an acceptable margin of safety in this patient population. This investigation is the first to prospectively validate the pharmacokinetics and toxicities of fixed-dose PMB in CF and will guide optimal use of this compound in the management of acute pulmonary exacerbations.
Detailed description
This study initially planned to include "Change in forced expiratory volume in one second (FEV1)" and "Non-response to therapy" as secondary outcome measures. These outcome measures were removed, as the small number of participants prohibited collection of significant data beyond what was collected for the baseline measures.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with CF lung disease receiving Polymyxin B (PMB) | – | Other: Blood DrawParticipants receiving polymyxcin B as part of standard of care treatment for CF exacerbation will have blood drawn measure blood concentrations of PMB |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- CF patients admitted to the University of Michigan hospitals requiring polymyxin B as part of clinical care
Key inclusion criteria (3 listed)
- Adults ≥ 18 years of age.
- Diagnosis of CF.
- Receiving polymyxin B in the course of routine care.
Key exclusion criteria (3 listed)
- Evidence of acute kidney injury during the 48 hours prior to and following initiation of PMB therapy.
- Extracorporeal organ support (including ECMO, iHD, and CRRT).
- Pregnant or breastfeeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood DrawBlood samples will be collected from enrolled patients at 5 time points during a single dosing interval: 1. Prior to start of infusion 2. End of infusion 3. One hour after end of infusion 4. Three hours after end of infusion 5. Eight hours after start of infusion | Other | Patients with CF lung disease receiving Polymyxin B (PMB) |
Primary outcome
Polymyxin B compartmental population pharmacokinetics model
Time frame: From immediately prior to a dose of therapy through 8 hours after therapy, approximately 8 hours
The population pharmacokinetics of polymyxin B will be modeled based on the observed polymyxin B1 and B2 concentrations in plasma from enrolled patients who receive at least 1 dose of polymyxin B
4 secondary outcomes
Acute kidney injury
Time frame: From 48 hours after first dose through 48 hours after end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
Neurotoxicity
Time frame: From initiation of first dose through end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
Change in forced expiratory volume in one second (FEV1)
Time frame: FEV1 at baseline to 7 days post treatment, approximately 14-90 days in total
Non-reponse to therapy
Time frame: From initiation of therapy through end of therapy, approximately 7-21 days depending on prescribed length of therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- Results publication: PubMed 34252297Crass RL, Al Naimi T, Wen B, Souza E, Murray S, Pai MP, Jia S. Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0079221. doi: 10.1128/AAC.00792-21. Epub 2021 Jul 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shijing Jia principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis and Polymyxin B, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Polymyxin B compartmental population pharmacokinetics model (time frame: From immediately prior to a dose of therapy through 8 hours after therapy, approximately 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04335370, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2023.