Multidrug Resistant Gram Negative Bacterial Infections Clinical Trial
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.
| Verified date | April 2017 |
| Source | Parc de Salut Mar |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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:
1. 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.
2. 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.
| Status | Completed |
| Enrollment | 101 |
| Est. completion date | August 2015 |
| Est. primary completion date | January 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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. Exclusion Criteria: - 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 |
| Country | Name | City | State |
|---|---|---|---|
| Spain | Hospital de Sant Pau | Barcelona | |
| Spain | Hospital del Mar | Barcelona | |
| Spain | Hospital de Granollers | Granollers | Barcelona |
| Lead Sponsor | Collaborator |
|---|---|
| Parc de Salut Mar |
Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Subjects with clinical outcome of cure in the two arms. | The proportion of subjects with clinical outcome of cure in the two arms | Clinical cure will be assessed at the end of the treatment with colistin with and expected average of 10 days. | |
| Secondary | The proportion of subjects with microbiological outcome of success in the two arms | End of treatment with CMS (sodium colistimetate), at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks). | ||
| Secondary | The proportion of subjects with all-cause mortality in the two arms | End of treatment with CMS (sodium colistimetate), at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks). | ||
| Secondary | The proportion of subjects with mortality directly attributable to infection in the two arms | End of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks). | ||
| Secondary | The proportion of subjects with renal toxicity according to RIFLE criteria associated with colistin in the two arms | 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). | ||
| Secondary | Number of patients who reach a plasma concentration of colistin within targets (ratio Cmax/CMI= 8-10) in the two arms | During CMS treatment | ||
| Secondary | 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). | 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). | |
| Secondary | To correlate the PK/PD ratio of colistin (Cmax/CMI) with clinical outcomes and/or nephrotoxicity | At the end of treatment with CMS, at discharge and 30 days after the end of treatment with CMS (an average of 2 weeks). |