E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Exposure to oral antibiotics will be investigated in infectious patients when they are febrile compared to when they are afebrile. The infection itself is unspecified. |
Blootstelling aan orale antibiotica zal onderzocht worden in infectieuze patiënten wanneer zij koorts hebben vergeleken met wanneer zij koorts vrij zijn. De infectie zelf is niet gespecificeerd. |
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E.1.1.1 | Medical condition in easily understood language |
Exposure to antibiotics taken by mouth will be investigated in infectious patients with fever compared to when they have no fever. The infection can be of any kind. |
Blootstelling aan antibiotica in tabletvorm zal onderzocht worden in patiënten wanneer zij koorts hebben vergeleken met wanneer zij geen koorts hebben. Dit kan elke infectie zijn. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
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 |
The primary objective is to determine if the exposure to oral ciprofloxacin and amoxicillin is altered in hospitalized non-critically ill, febrile patients in need of IV antibiotics when they are acutely ill and febrile, compared to when they are afebrile. |
Het primaire doel is om te onderzoeken of bij klinische patiënten met een infectie, die niet in kritieke toestand verkeren, de blootstelling aan orale ciprofloxacine en amoxicilline anders is wanneer zij acuut ziek zijn en koorts hebben ten opzichte van wanneer zij koorts vrij geworden zijn. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to determine if target attainment can be achieved with current oral treatment dosage regimens. |
Het secundaire doel is om te onderzoeken of effectieve spiegels worden bereikt met de huidige doseringen van de orale antibiotica. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥18 years Acute febrile illness, defined as a temperature ≥38.5 and in need of IV antibiotic therapy for an infection for which amoxicillin or ciprofloxacin are registered treatments Admitted to the internal medicine (including gastroenterology and pulmonology ward) Able to take oral medication, that is no abdominal pathology or history of abdominal pathology that may alter absorption (i.e. vomiting, mucositis, diarrhoea, malabsorption syndrome, former abdominal surgery affecting absorption) Able and willing to give informed consent |
Leeftijd ≥18 jaar Acute infectie, gedefinieerd als een temperatuur ≥38.5 en een indicatie voor IV antibiotica waarvoor ciprofloxacine of amoxicilline een geregistreerde behandeling is. Opgenomen op de interne afdeling (inclusief de afdelingen longziekten en maag-darm-leverziekten In staat om orale medicatie in te nemen: geen abdominale pathologie of voorgeschiedenis van abdominale pathologie welke mogelijk de absorptie van van de orale toediening beinvloedt (braken, mucositis, diarree, malabsorptie) In staat om informed consent te kunnen en willen geven.
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E.4 | Principal exclusion criteria |
Critically ill patients, admitted to the ICU, or infectious patients of the general ward who became critically ill and got transferred to the ICU during the research period. Comorbidity affecting absorption: hepatic impairment, i.e. active hepatitis, hepatic failure, liver cirrhosis or severe renal impairment (GFR <30), Neutropenic patients (neutrophil count <1000/µl) and patients treated with chemotherapy within 28 days prior to the study. Contraindications to use ciprofloxacin or amoxicillin o Ciprofloxacin: allergy to fluoroquinolones, concomitant administration of tizanidine o Amoxicillin: allergy to penicillins or proven allergy to another beta-lactam agent (e.g. cephalosporin, carbapenem or monobactam). Penicillin/fluoroquinolone treatment during the week prior to study enrolment Pregnancy History of alcohol and drug abuse. |
Patienten die zich in een kritisch zieke toestand verkeren opgenomen op de intensive care, of infectieuze patienten van de interne afdeling die tijdens beloop van de opname moeten worden overgeplaatst naar de intensive care. Comorbiditeit die de absorptie van orale antibiotica kan beïnvloeden: actieve hepatitis, leverfalen, lever cirrose, ernstige nierfunctieafwijking (eGFR<30) Neutropene patienten (neurtrofiel getal <1000/ul) en patienten die behandeld zijn met chemotherapie binnen 28 dagen voor de start van de studie. - Contraindicaties om ciprofloxacine of amxocilline toegediend te krijgen: o ciprofloxacine: fluorquinolonen allergie, gelijktijdige toediening van tizanidine o amoxicilline: allergie voor penicillines of een andere beta-lactam Behandeling met penicilline/fluorquinolone de week voor de start van de studie Zwangerschap Voorgeschiedenis van alcohol en drugs misbruik |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the AUC, calculated after oral administration of ciprofloxacin and amoxicillin, which will be compared between the febrile and afebrile phase. |
De primaire paramater is de AUC, berekend na de orale toediening van ciprofloxacine en amoxicilline. De AUC waarden van de koorts- en de koortsvrije fase zullen vergeleken worden. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be evaluated after all patients of the initial sample size calculation have been included. |
Nadat alle patiënten van de initiële sample size calculatie zijn geincludeerd. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are the Cmax and Tmax, calculated after oral administration of ciprofloxacin and amoxicillin, which will be compared between the febrile and afebrile phase. In addition, the percentage of patients that achieve target attainment will be assessed in both phases. |
De secundaire parameters zijn de Cmax en Tmax, berekend na de orale toediening van ciprofloxacine en amoxicilline en het percentage patienten waarbij het orale antibioticum effectieve spiegels bereikt. De Cmax, Tmax en percentage patiënten met effectieve spiegels van de koorts- en de koortsvrije fase zullen vergeleken worden. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be evaluated after all patients of the initial sample size calculation have been included. |
Nadat alle patiënten van de initiële sample size calculatie zijn geincludeerd. |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Longitudinal cohort study with repeated measurements |
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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.8.5 | 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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |