E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Antibiotic prophylaxis for CABG surgery |
Antibiotikaprophylaxe bei CABG Operationen |
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E.1.1.1 | Medical condition in easily understood language |
Antibiotic prophylaxis for coronary bypass surgery |
Antibiotikaprophylaxe bei Koronarbypass Operationen |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036894 |
E.1.2 | Term | Prophylactic antibiotic therapy |
E.1.2 | System Organ Class | 100000004865 |
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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 |
To measure free, microbiologically active concentrations of ceftaroline in plasma, subcutaneous tissue and lung parenchyma in order to evaluate whether adequate concentrations of ceftaroline are achieved in this special cohort of patients for antibiotic prophylaxis and treatment of complicated skin and soft-tissue infections and community acquired pneumonia. |
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E.2.2 | Secondary objectives of the trial |
- To compare free concentrations of ceftaroline in subcutaneous tissue with a presumed perfusion deficit (on the left side of sternotomy incision due to LIMA preparation) and subcutaneus tissue with normal perfusion (on the right side of the sternotomy incision)
- To compare bolus- and continuous administration of ceftaroline using identical doses |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Written informed consent -Planned coronary artery bypass grafting with left internal mammary artery bypass -Planned use of cardiopulmonary bypass -Age: > 18 and < 90 years -Ejection fraction > 40% |
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E.4 | Principal exclusion criteria |
-Inability to give informed consent -Know allergy to cephalosporins or penicillin or ceftaroline -Preoperative antibiotic therapy -Signs of infection preoperatively -Re-operation or emergency procedure -Planned use of bilateral internal mammary artery bypass -Preoperative renal failure -Chronic severe renal insufficiency including hemodialysis -Chronic severe liver disease -BMI > 35 -Long standing diabetes mellitus (> 7 years) and insulin-dependent diabetes mellitus -Pregnant women |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Perioperative pharmacokinetic profiles of ceftaroline in plasma, subcutaneous tissue and lung parenchyma |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
In the bolus-group, ceftaroline plasma and tissue concentrations will be drawn at baseline, in 30min intervals during administration of each bolus and every 2h after completion of the bolus until the next bolus. The last sample will be drawn 1440mins after the first administration. In the continuous group, ceftaroline plasma and tissue concentrations will be drawn at baseline, in 30min intervals for the first 10h of continuous adminstration and every 2h thereafter until 1440mins after the first administration. |
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E.5.2 | Secondary end point(s) |
- Difference of pharmacokinetics of ceftaroline between plasma, subcutaneous tissue and lung parenchyma - Difference of pharmacokinetic profiles between intermittent bolus administration and continuous administration of ceftaroline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
In the bolus-group, ceftaroline plasma and tissue concentrations will be drawn at baseline, in 30min intervals during administration of each bolus and every 2h after completion of the bolus until the next bolus. The last sample will be drawn 1440mins after the first administration. In the continuous group, ceftaroline plasma and tissue concentrations will be drawn at baseline, in 30min intervals for the first 10h of continuous adminstration and every 2h thereafter until 1440mins after the first administration. |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Bolus administration vs continuous administration of ceftaroline |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |