E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To evaluate feasibility of Moxifloxacin determination in septic patients
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Pilot phase: 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.
Main phase: To prospectively identify factors influencing tissue penetration of antimicrobials in patients with sepsis .
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the previously described TTPS score 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. 3) To determine kill rates of selected bacterial strains in vitro exposed to the time versus concentration profiles of Moxifloxacin determined in vivo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal exclusion criteria |
• Allergy against study drug. • Bleeding disorders which prohibit intramuscular implantation of the microdialysis probe
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |