Determination of Moxifloxacin concentrations in interstitial space fluid of muscle and subcutis in septic patients including a pilot phase

• Conditions: To evaluate feasibility of Moxifloxacin determination in septic patients

• Registration Number: EUCTR2010-022150-16-AT
• Lead Sponsor: Medizinische Universität Wien, Univ.Klinik f.klinische Pharmakologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-25
• Last Update Posted: 9 December 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Indication to Moxifloxacin therapy
•No Moxifloxacin therapy within the last 12 hours.
Severe sepsis or septic shock as diagnosed according to the criteria of ACCP/SCCM and the MAXSEP Study within 24 hours:
a) Severe sepsis
•Presence of microbiologically proven, clinically proven, or
suspected infection
•Presence of Systemic Inflammatory Response Syndrome
(SIRS) (fulfillment of at least two of the following criteria):
- hypo- (=36°C) or hyperthermia (=38°C)
- tachycardia (=90 bpm)
- tachypnea (=20 breaths/min) and/or an arterial pCO2 =4.3 kPa (32 mmHg) and/or mechanical ventilation
- leukocytosis =12,000/µl or leukopenia = 4,000/µl and/or a left shift in the differential white blood cell count =10 percent.
•Development of at least one organ dysfunction
within the last 24 hours (one of the following criteria had to be fulfilled):
- presence of acute encephalopathia with reduced vigilance, agitation, disorientation, delirium not explained by psychotropic medication
- thrombocytopenia = 100.000/µl or a drop in the thrombocyte count >30 percent within 24 hours not explained by hemorrhage
- arterial hypoxemia with an arterial pO2 <10 kPa (75 mmHg) when breathing room air or an oxygenation index (paO2/FiO2 = 33kPa (250 mmHg) not explained by presence of a pulmonary or cardial disease
- arterial hypotension with a systolic blood pressure = 90 mmHg or mean arterial blood pressure = 70 mmHg for at least one hour despite adequate fluid loading not explained by other causes of shock
- renal dysfunction with an urine output = 0.5 ml/kg/h for at least one hour despite adequate fluid loading and/or increase of serum creatinine more than twofold above the reference range of the local laboratory
- metabolic acidosis with a base deficit =5.0 mmol/l or a serum lactate =1.5fold above the reference range of the local laboratory.
b) Septic shock
•Presence of infection and SIRS as defined in severe
sepsis
•Presence of arterial hypotension with a systolic blood
pressure =90 mmHg or a mean arterial blood pressure =70 mmHg for at least 2 hours or administration of a vasopressor (dopamine =5 µg kg-1 min-1; norepinephrine, epinephrine, phenylephrine, or vasopressin in any dosage) to maintain systolic blood pressure =90 mmHg or mean arterial blood pressure =70 mmHg despite adequate fluid loading.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Allergy against study drug.
•Bleeding disorders which prohibit intramuscular implantation of the microdialysis probe

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 1)To evaluate the previously described TTPS score<br>2)To measure concentrations of Moxifloxacin in the interstitial space fluid of subcutaneous adipose tissue- and skeletal muscle and to relate these concentrations to corresponding plasma concentrations.<br>3)To determine kill rates of selected bacterial strains in vitro exposed to the time versus concentration profiles of Moxifloxacin determined in vivo.<br><br>;Primary end point(s): Area under the concentration time curve (AUC), maximum concentration (Cmax), half-life (t1/2) in the microdialysate and plasma after single dose and at steady state.;Main Objective: Pilot phase: <br>To evaluate feasibility of Moxifloxacin determination in septic patients in a multicenter setting and to explore pharmacokinetic variability to determine sample size for the main phase. <br><br>Main phase:<br>To prospectively identify factors influencing tissue penetration of antimicrobials in patients with sepsis .<br><br>