Multidrug Resistant Gram Negative Bacterial InfectionsNCT01845246
Multicentric Study About the Usefulness of Monitoring Plasma Levels of Colistin and Sodium Colistimethate in Patients With Infections Due to Multi-drug Resistant Gram Negative Bacilli, Treated With Colistin
A study testing Prospective TDM Arm of colistin in people with Multidrug Resistant Gram Negative Bacterial Infections, run by Parc de Salut Mar at 3 sites in Spain.
Trial summary
Objectives: Main objective: to assess the impact of an intervention for optimizing the dosing of colistin based on its plasma levels in patients with infections due to multi-drug resistant gram negative bacilli. The impact will be evaluated in terms of clinical and microbiological outcome, and toxicity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multidrug Resistant Gram Negative Bacterial Infections
- What is being tested?
- Prospective TDM Arm of colistin
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 3 sitesSpain
- Study dates
- Jan 2012to 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
- Male or female ≥18 years of age.
- Hospitalized patients with an active infection caused by MDR-BGN
- Treatment with intravenous CMS for at least 3 consecutive days
- Evidence of a personally signed and dated informed consent document in accordance with local regulatory and legal requirements indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
Who cannot join
- Patients colonized by a MDR-BGN and no signs/symptoms of an active infection
- Treatment with intravenous CMS for least than 3 days
- Patients with polymicrobial infections (with an isolated microorganism different from the MDR-BGN).
- Patients with a glomerular filtration rate at baseline less than 10ml/min or those requiring renal replacement therapies.
- Known history of allergy, hypersensitivity or serious reaction to polymyxins.
- Patients treated with nebulized CMS in addition to intravenous CMS.
- Patients who have already participated in this trial.
- Patients without a personally signed and dated informed consent document
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital del Mar
Barcelona, Barcelona, 08003
Hospital de Sant Pau
Barcelona, Barcelona, 08025
Hospital de Granollers
Granollers, Barcelona, 08400
About this study
Official title: Multicentric Study About the Usefulness of Monitoring Plasma Levels of Colistin and Sodium Colistimethate in Patients With Infections Due to Multi-drug Resistant Gram Negative Bacilli, Treated With Colistin.
Objectives: Main objective: to assess the impact of an intervention for optimizing the dosing of colistin based on its plasma levels in patients with infections due to multi-drug resistant gram negative bacilli. The impact will be evaluated in terms of clinical and microbiological outcome, and toxicity.
Secondary objectives:
Read more
- To determine the percentage of patients reaching plasma levels considered adequate (Cmax / MIC 8-10) for the treatment of infections due to gram-negative bacilli susceptible to colistin, in the cohort of patients treated with standard doses of this drug without adjusting the dose.
- To analyze the possible emergence of bacterial resistance to this drug and its relationship to the calculated colistin pharmacokinetic and pharmacodynamic indexes.
Methods:
Design: open controlled trial, blinded for the analyst, to be performed at thre tertiary care Hospitals in Barcelona.
Subjects: Patients attended consecutively between 2012 and 2013 infected with multi-drug resistant gram negative bacilli and treated with colistin.
Sample size: 142 cases. Intervention: Once detected the infection requiring treatment with colistin, patients will be randomized to receive the intervention or not, with a 1:1 ratio. The intervention will be performed by an Infectious Diseases physician and will consist in a recommendation on the dose of colistin based on its plasma levels 48 hours after treatment onset.
Variables: peak and through colistin levels 48 hours after treatment onset, clinical, analytical and microbiological data at baseline and during follow-up of the patients.
Outcome measures: clinical, microbiological and toxicity data. Analysis: Comparison of patient characteristics and outcome variables between patients who had received the intervention and those who had not. The analysis will be done by intention to treat, by biological effectiveness and by compliance with the protocol.
- Being tested
- Prospective TDM Arm of colistin
- Keywords
- Colistin, Polymyxins, Therapeutic drug monitoring, Multi Drug resistant Gram negative bacterial infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prospective TDM Arm of colistinDevice
| Study group | Role | What they receive |
|---|---|---|
| Standard doses of colistin will be used. | No intervention | Patients will receive the standard doses of colistin without TDM (Therapeutic drug monitoring). |
| Prospective TDM (Therapeutic drug monitoring)of colistin arm | Experimental | CMS dose will be adjusted based on protocol obtained TDM levels. Receives: Device: Prospective TDM Arm of colistin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjects with clinical outcome of cure in the two arms.
The proportion of subjects with clinical outcome of cure in the two arms
Measured: Clinical cure will be assessed at the end of the treatment with colistin with and expected average of 10 days.
Secondary outcomes (7)
The proportion of subjects with microbiological outcome of success in the two arms
Measured: End of treatment with CMS (sodium colistimetate), at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
The proportion of subjects with all-cause mortality in the two arms
Measured: End of treatment with CMS (sodium colistimetate), at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
The proportion of subjects with mortality directly attributable to infection in the two arms
Measured: End of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
The proportion of subjects with renal toxicity according to RIFLE criteria associated with colistin in the two arms
Measured: During CMS treatment, at the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
Number of patients who reach a plasma concentration of colistin within targets (ratio Cmax/CMI= 8-10) in the two arms
Measured: During CMS treatment
Number of patients with emergence of resistance to colistin in the two arms
Emergence of resistance is defined as the detection during treatment of MDR-GNB (Multi-drug Resistant Gram Negative Bacilli) isolates showing resistance to colistin (MIC >2 mg/l).
Measured: During CMS treatment, at the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
To correlate the PK/PD ratio of colistin (Cmax/CMI) with clinical outcomes and/or nephrotoxicity
Measured: At the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startJan 2012
- Primary completionJan 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multidrug Resistant Gram Negative Bacterial InfectionsStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan Pablo Horcajada, Parc de Salut Mar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01845246
- Sponsor's protocol ID
- PSM-COL-MC-12
- Status last verified
- Apr 2017
- First submitted
- 16 Apr 2013
- Last updated
- 12 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentric Study About the Usefulness of Monitoring Plasma Levels of Colistin and Sodium Colistimethate in Patients With Infections Due to Multi-drug Resistant Gram Negative Bacilli, Treated With Colistin.
- ClinicalTrials.gov ID
- NCT01845246
- Acronym / sponsor ID
- PSM-COL-MC-12
- Keywords
- Colistin, Polymyxins, Therapeutic drug monitoring, Multi Drug resistant Gram negative bacterial infections
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 3 May 2013 (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.
Objectives: Main objective: to assess the impact of an intervention for optimizing the dosing of colistin based on its plasma levels in patients with infections due to multi-drug resistant gram negative bacilli. The impact will be evaluated in terms of clinical and microbiological outcome, and toxicity.
Secondary objectives:
- To determine the percentage of patients reaching plasma levels considered adequate (Cmax / MIC 8-10) for the treatment of infections due to gram-negative bacilli susceptible to colistin, in the cohort of patients treated with standard doses of this drug without adjusting the dose.
- To analyze the possible emergence of bacterial resistance to this drug and its relationship to the calculated colistin pharmacokinetic and pharmacodynamic indexes.
Methods:
Design: open controlled trial, blinded for the analyst, to be performed at thre tertiary care Hospitals in Barcelona.
Subjects: Patients attended consecutively between 2012 and 2013 infected with multi-drug resistant gram negative bacilli and treated with colistin.
Sample size: 142 cases. Intervention: Once detected the infection requiring treatment with colistin, patients will be randomized to receive the intervention or not, with a 1:1 ratio. The intervention will be performed by an Infectious Diseases physician and will consist in a recommendation on the dose of colistin based on its plasma levels 48 hours after treatment onset.
Variables: peak and through colistin levels 48 hours after treatment onset, clinical, analytical and microbiological data at baseline and during follow-up of the patients.
Outcome measures: clinical, microbiological and toxicity data. Analysis: Comparison of patient characteristics and outcome variables between patients who had received the intervention and those who had not. The analysis will be done by intention to treat, by biological effectiveness and by compliance with the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard doses of colistin will be used. | No intervention | –Patients will receive the standard doses of colistin without TDM (Therapeutic drug monitoring). |
| Prospective TDM (Therapeutic drug monitoring)of colistin arm | Experimental | Device: Prospective TDM Arm of colistinCMS dose will be adjusted based on protocol obtained TDM levels. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female ≥18 years of age.
- Hospitalized patients with an active infection caused by MDR-BGN
- Treatment with intravenous CMS for at least 3 consecutive days
- Evidence of a personally signed and dated informed consent document in accordance with local regulatory and legal requirements indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
Key exclusion criteria (8 listed)
- Patients colonized by a MDR-BGN and no signs/symptoms of an active infection
- Treatment with intravenous CMS for least than 3 days
- Patients with polymicrobial infections (with an isolated microorganism different from the MDR-BGN).
- Patients with a glomerular filtration rate at baseline less than 10ml/min or those requiring renal replacement therapies.
- Known history of allergy, hypersensitivity or serious reaction to polymyxins.
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 |
|---|---|---|
| Prospective TDM Arm of colistin | Device | Prospective TDM (Therapeutic drug monitoring)of colistin arm |
Primary outcome
Subjects with clinical outcome of cure in the two arms.
Time frame: Clinical cure will be assessed at the end of the treatment with colistin with and expected average of 10 days.
The proportion of subjects with clinical outcome of cure in the two arms
7 secondary outcomes
The proportion of subjects with microbiological outcome of success in the two arms
Time frame: End of treatment with CMS (sodium colistimetate), at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
The proportion of subjects with all-cause mortality in the two arms
Time frame: End of treatment with CMS (sodium colistimetate), at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
The proportion of subjects with mortality directly attributable to infection in the two arms
Time frame: End of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
The proportion of subjects with renal toxicity according to RIFLE criteria associated with colistin in the two arms
Time frame: During CMS treatment, at the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
Number of patients who reach a plasma concentration of colistin within targets (ratio Cmax/CMI= 8-10) in the two arms
Time frame: During CMS treatment
Number of patients with emergence of resistance to colistin in the two arms
Time frame: During CMS treatment, at the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
To correlate the PK/PD ratio of colistin (Cmax/CMI) with clinical outcomes and/or nephrotoxicity
Time frame: At the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks).
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 12 Apr 2017.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prospective TDM Arm of colistin in people with Multidrug Resistant Gram Negative Bacterial Infections, run by Parc de Salut Mar at 3 sites in Spain.
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 8 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 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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?
Subjects with clinical outcome of cure in the two arms. (time frame: Clinical cure will be assessed at the end of the treatment with colistin with and expected average of 10 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2017.