E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
perioperative antibiotic prophylaxis during coronary artery bypass grafting |
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E.1.1.1 | Medical condition in easily understood language |
perioperative antibiotic prophylaxis during heart surgery |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036894 |
E.1.2 | Term | Prophylactic antibiotic therapy |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011077 |
E.1.2 | Term | Coronary artery bypass |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064736 |
E.1.2 | Term | Antibiotic prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011078 |
E.1.2 | Term | Coronary artery disease |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 evaluate the target tissue concentration of cefazolin and linezold in sternal bone marrow of patients undergoing coronary artery bypass grafting - To assess the impact of left internal mammary artery preparation on target tissue antibiotic concentration in sternal spongiosa
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E.2.2 | Secondary objectives of the trial |
- Pharmacokinetics in dual antibiotic prophylaxis |
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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 - Planned used of cardiopulmonary bypass - Age ≥ 18 and ≤ 90 years - No pre-existing liver or kidney disease - Left ventricular ejection fraction > 40% - No pre-existing osteoporosis requiring therapy
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E.4 | Principal exclusion criteria |
- Preoperative antibiotic treatment - Preoperative signs of infection - Inability to give informed consent or missing informed consent - Know allergy to cephalosporins, penicillin or Linezolid - Re-operation - Additional planned valve surgery - Preoperative renal replacement therapy - BMI > 40 - Long standing diabetes mellitus (> 7 years) - Preoperative osteoporosis requiring therapy - Age <18 or >90 - Chronic severe liver or renal insufficiency - Childbearing potential - Drug or alcohol abuses - Psychiatric disease - Treatment with MAO – inhibiting or serotonergic medication
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E.5 End points |
E.5.1 | Primary end point(s) |
- Perioperative time to concentration profiles of cefazolin and linezolid in plasma and additionally in sternal spongiosa - Difference of tissue concentration of linezolid between left and right sternal spongiosa tissue - Difference of tissue concentration of cefazolin between left and right sternal spongiosa tissue - Difference of antibiotic penetration (cefazolin versus linezolid) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cefazolin and Linezolid plasma levels will be drawn at baseline and at 30, 60, 90, 120, 150, 180 min after drug administration followed by blood draws every two hours thereafter for 24 hours. Then again at 720, 750, 780, 810, 840 hours after the first administration and then every two hours until 1440 mins after the first administration (see time schedule in protocol) |
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E.5.2 | Secondary end point(s) |
- Pharmacokinetics in dual antibiotic prophylaxis |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cefazolin and Linezolid plasma levels will be drawn at baseline and at 30, 60, 90, 120, 150, 180 min after drug administration followed by blood draws every two hours thereafter for 24 hours. Then again at 720, 750, 780, 810, 840 hours after the first administration and then every two hours until 1440 mins after the first administration (see time schedule in protocol) |
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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) | 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 | No |
E.8.1.2 | Open | No |
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 | No |
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 | 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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |