BacteremiaNCT00235690
Optimizing Dosing of Colistin for Infections Resistant to All Other Antibiotics, Approved NIH Protocol Dated 12.06.07(DMID Protocol #07-0036)
A study testing Blood draws and Blood draw in people with Bacteremia and Pseudomonas Infections, run by University of Pittsburgh at 1 site in United States.
Trial summary
More than 80 patients at the University of Pittsburgh Medical Center have been infected with Pseudomonas aeruginosa, lacking susceptibility to all commercially available antibiotics except "colistin". This antibiotic was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacteremia, Pseudomonas Infections
- What is being tested?
- Blood draws and Blood draw
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Aug 2015
- Phase
- Interventional
- 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
Who may be able to join
- Males or females greater than 18 years of age.
- All patients will remain in the hospital for pharmacokinetic sampling.
- All subjects must be on the medication colistin as part of their standard of care.
- All individuals approached for participation shall be able to read and comprehend English.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Pharmacokinetics and Pharmacodynamics of Intravenous Colistin- Pilot Study
More than 80 patients at the University of Pittsburgh Medical Center have been infected with Pseudomonas aeruginosa, lacking susceptibility to all commercially available antibiotics except "colistin". This antibiotic was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no dosing recommendations for patients requiring renal replacement therapy (either intermittent hemodialysis or continuous venovenous hemofiltration). Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the University of Pittsburgh, are performing a pilot study of the pharmacokinetics of intravenous CMS/colistin in patients requiring this antibiotic for clinical purposes. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Concentrations in pulmonary epithelial lining fluid will also be determined in patients with pneumonia. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia which developed these assays. A submission is being made to the National Institutes of Health (NIH) for funding of a multicenter study which will address this research question with a greater sample size. The study proposed here is a pilot study in order to prove the feasibility of the research approach and to provide preliminary data for the NIH proposal.
Read the detailed description
At baseline (upon signing informed consent), the following information will be collected: Demographic data - age, sex, height, weight, state of birth, underlying illnesses, underlying infection, immunosuppression, antibiotic use, laboratory results, current medication use, any other prior medical problems/history and clinical outcomes.
The research coordinator will contact the patient on days 14, 28 and 90 days after the infection to determine clinical outcome. If the patient is still an inpatient the research coordinator will visit the patient in their hospital room to evaluate the patient's health status. This visit will take about 10 minutes. If the patient has been discharged from the hospital, the patient will be contacted by telephone by the research coordinator to determine the health status, if no recent electronic medical record exists. This telephone contact will take about 10 minutes.
Blood work and microbiologic samples to be collected:
Collection of six samples of 3 mL blood on the third or fourth day of colistin therapy will occur. These samples will be collected:
- immediately pre-dose,
- at the end of the colistin infusion,
- 30 minutes after the end of the colistin infusion,
- 60 minutes after the end of the colistin infusion,
- 4 hours after the end of the colistin infusion,
- 12 hours after the end of the colistin infusion (or immediately prior to the next dose if the drug is being given every 12 hours).
Indwelling venous and arterial access lines, if already in place, will be utilized for the pharmacological study's blood draws.
Rationale: The samples will be utilized for quantification of plasma levels of colistin.
Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy. These samples are two sets of blood cultures if the patient had bacteremia, a mini-BAL for quantitative bacterial culture if the patient had pneumonia and a cerebrospinal fluid collection if the patient had Gram negative meningitis and has a cerebrospinal fluid drain in situ. Additionally, these samples will be used to determine the concentrations of colistin and CMS at the site of infection. A 3mL blood sample will be taken at the same time as these specimen collections to determine concomitant serum concentrations of colistin and CMS.
Rationale: These samples will be used to determine if there has been rapid bacteriologic clearance of infection and to determine the concentrations of drug at the site of infection.
The blood samples will be processed and stored in a -80° C freezer in a secured laboratory under the supervision of the principal investigator. These samples will then be sent to the laboratory of Drs Jian Li and Roger Nation in Melbourne, Australia, to determine the amount of colistin and CMS that reached the participant's blood following dose administration. All samples will be sent de-identified.
All samples will be analyzed to obtain the amount of colistin and CMS found in the blood. The biologic samples will be under the control of the principal investigator of this research project. To protect confidentiality, all personal identifiers (i.e., name, social security number, and birth date) will be removed (de-identified) and replaced with a specific code number. The information linking these code numbers to the corresponding subjects' identities will be kept in a separate, secure location. The investigators on this study will keep the samples indefinitely. All samples sent outside of the UPMC facility will be de-identified. If a subject withdraws and provides the request in writing, samples collected and not already processed will be destroyed. All samples at UPMC will be kept in the investigator's laboratory located in Scaife Hall, Room 812, 3550 Terrace Street. All patients will be seen at the UPMC facility while they are inpatients.
Other items to be collected for study purposes:
Microbiology - the organism that caused the infection will be sub-cultured in the clinical microbiology laboratory (after the diagnosis has been obtained since the microbiology lab would otherwise destroy the culture) and provided to the investigators. All subsequent Gram negative bacterial isolates will be sub-cultured and stored for similar purposes.
An unopened vial of colistin from the same batch as used for the patient will be collected for analysis, so the actual dose of colistin can be calculated.
- Conditions
- Bacteremia, Pseudomonas Infections
- Being tested
- Blood draws, Blood draw
- Medical subject headings
- Bacteremia, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawsProcedure or surgery
PK samples obtained around a clinical dosing of colistin
Blood drawOther
PK blood samples will be obtained around a clinical dosing of colistin
| Study group | Role | What they receive |
|---|---|---|
| blood draws | Other | all patients enrolled will have PK blood samples obtained around a colistin dosing Receives: Procedure: Blood draws; Other: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
To provide pharmacokinetic data on intravenous (IV) CMS/colistin
Measured: 5 years
Secondary outcomes (1)
Determine if CMS/colistin dosing is suboptimal in ill patients
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2005 (estimated)
- Study startJun 2008
- Primary completionAug 2015
- Study completionAug 2015
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 BacteremiaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fernanda Silveira, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00235690
- Sponsor's protocol ID
- IRB# 0509011
- Other IDs
- NIH
- Status last verified
- Dec 2015
- First submitted
- 6 Oct 2005
- Last updated
- 17 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, Turnidge JD, Forrest A, Silveira FP. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis. 2016 Mar 1;62(5):552-558. doi: 10.1093/cid/civ964. Epub 2015 Nov 25.
PubMed 26607424
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of Intravenous Colistin- Pilot Study
- ClinicalTrials.gov ID
- NCT00235690
- Acronym / sponsor ID
- IRB# 0509011
- Conditions
- Bacteremia, Pseudomonas Infections
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 10 Oct 2005 (estimated)
- 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.
More than 80 patients at the University of Pittsburgh Medical Center have been infected with Pseudomonas aeruginosa, lacking susceptibility to all commercially available antibiotics except "colistin". This antibiotic was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no dosing recommendations for patients requiring renal replacement therapy (either intermittent hemodialysis or continuous venovenous hemofiltration). Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the University of Pittsburgh, are performing a pilot study of the pharmacokinetics of intravenous CMS/colistin in patients requiring this antibiotic for clinical purposes. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Concentrations in pulmonary epithelial lining fluid will also be determined in patients with pneumonia. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia which developed these assays. A submission is being made to the National Institutes of Health (NIH) for funding of a multicenter study which will address this research question with a greater sample size. The study proposed here is a pilot study in order to prove the feasibility of the research approach and to provide preliminary data for the NIH proposal.
Detailed description
At baseline (upon signing informed consent), the following information will be collected: Demographic data - age, sex, height, weight, state of birth, underlying illnesses, underlying infection, immunosuppression, antibiotic use, laboratory results, current medication use, any other prior medical problems/history and clinical outcomes.
The research coordinator will contact the patient on days 14, 28 and 90 days after the infection to determine clinical outcome. If the patient is still an inpatient the research coordinator will visit the patient in their hospital room to evaluate the patient's health status. This visit will take about 10 minutes. If the patient has been discharged from the hospital, the patient will be contacted by telephone by the research coordinator to determine the health status, if no recent electronic medical record exists. This telephone contact will take about 10 minutes.
Blood work and microbiologic samples to be collected:
Collection of six samples of 3 mL blood on the third or fourth day of colistin therapy will occur. These samples will be collected:
- immediately pre-dose,
- at the end of the colistin infusion,
- 30 minutes after the end of the colistin infusion,
- 60 minutes after the end of the colistin infusion,
- 4 hours after the end of the colistin infusion,
- 12 hours after the end of the colistin infusion (or immediately prior to the next dose if the drug is being given every 12 hours).
Indwelling venous and arterial access lines, if already in place, will be utilized for the pharmacological study's blood draws.
Rationale: The samples will be utilized for quantification of plasma levels of colistin.
Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy. These samples are two sets of blood cultures if the patient had bacteremia, a mini-BAL for quantitative bacterial culture if the patient had pneumonia and a cerebrospinal fluid collection if the patient had Gram negative meningitis and has a cerebrospinal fluid drain in situ. Additionally, these samples will be used to determine the concentrations of colistin and CMS at the site of infection. A 3mL blood sample will be taken at the same time as these specimen collections to determine concomitant serum concentrations of colistin and CMS.
Rationale: These samples will be used to determine if there has been rapid bacteriologic clearance of infection and to determine the concentrations of drug at the site of infection.
The blood samples will be processed and stored in a -80° C freezer in a secured laboratory under the supervision of the principal investigator. These samples will then be sent to the laboratory of Drs Jian Li and Roger Nation in Melbourne, Australia, to determine the amount of colistin and CMS that reached the participant's blood following dose administration. All samples will be sent de-identified.
All samples will be analyzed to obtain the amount of colistin and CMS found in the blood. The biologic samples will be under the control of the principal investigator of this research project. To protect confidentiality, all personal identifiers (i.e., name, social security number, and birth date) will be removed (de-identified) and replaced with a specific code number. The information linking these code numbers to the corresponding subjects' identities will be kept in a separate, secure location. The investigators on this study will keep the samples indefinitely. All samples sent outside of the UPMC facility will be de-identified. If a subject withdraws and provides the request in writing, samples collected and not already processed will be destroyed. All samples at UPMC will be kept in the investigator's laboratory located in Scaife Hall, Room 812, 3550 Terrace Street. All patients will be seen at the UPMC facility while they are inpatients.
Other items to be collected for study purposes:
Microbiology - the organism that caused the infection will be sub-cultured in the clinical microbiology laboratory (after the diagnosis has been obtained since the microbiology lab would otherwise destroy the culture) and provided to the investigators. All subsequent Gram negative bacterial isolates will be sub-cultured and stored for similar purposes.
An unopened vial of colistin from the same batch as used for the patient will be collected for analysis, so the actual dose of colistin can be calculated.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| blood draws | Other | Procedure: Blood draws, Other: Blood drawall patients enrolled will have PK blood samples obtained around a colistin dosing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females greater than 18 years of age.
- All patients will remain in the hospital for pharmacokinetic sampling.
- All subjects must be on the medication colistin as part of their standard of care.
- All individuals approached for participation shall be able to read and comprehend English.
Key exclusion criteria (0 listed)
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 drawsPK samples obtained around a clinical dosing of colistin | Procedure or surgery | blood draws |
| Blood drawPK blood samples will be obtained around a clinical dosing of colistin | Other | blood draws |
Primary outcome
To provide pharmacokinetic data on intravenous (IV) CMS/colistin
Time frame: 5 years
1 secondary outcome
Determine if CMS/colistin dosing is suboptimal in ill patients
Time frame: 5 years
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 17 Dec 2015.
- Derived from this study: PubMed 26607424Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, Turnidge JD, Forrest A, Silveira FP. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis. 2016 Mar 1;62(5):552-558. doi: 10.1093/cid/civ964. Epub 2015 Nov 25.
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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.
Fernanda Silveira, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood draws and Blood draw in people with Bacteremia and Pseudomonas Infections, run by University of Pittsburgh 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 4 inclusion and 0 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 17 Dec 2015. 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?
To provide pharmacokinetic data on intravenous (IV) CMS/colistin (time frame: 5 years). 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 NCT00235690, 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 17 Dec 2015.