How antibiotics affect bacterial flora, immune system of the lung and infections due to mechanical ventilatio
- Conditions
- mechanically ventilated patientsTherapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2018-000492-32-DE
- Lead Sponsor
- Charité-Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
patients informed consent
age = 18 years
negative result of pregnany test in women of childbearing potential (WOCBP)
no participation in other clinical trials 30 days prior and after
on the day of enrolment at least intermittendly mechanical ventilation via tracheostomy
on the day of enrolment, hospitalization at Charité University hospital for at least 24hrs
state of clinical stability or state of clinical improvement with very high likelihood of development of a state of clinical stability
AND EITHER
=90 no antibiotic therapy
OR
on the day of inclusion completed course of antibiotic therapy that fulfills all of the following criteria:
7-10 days of antibiotic therapy with antimicrobial activity against Gram-negative, Gram-positive and anaerobic bacteria
Treatment according to marketing authorisation
Treatment according to SmPC
Treatment with trade product holding a marketing authorisation in original package
Treatment ended = 5x elimination half-time of the trade product prior AND not more than 72hrs prior to inclusion
Treatment with at least one of the following active substances (alphabetic order, same order as in Modul 1)
•Amoxicillin/Clavulansäure p.o.
•Ampicillin/Sulbactam i.v.
•Cefazolin i.v.
•Cefepim i.v.
•Ceftazidim i.v.
•Ceftazidim/Avibactam i.v.
•Ceftolozan/Tazobactam i.v.
•Ceftriaxon i.v.
•Ciprofloxacin p.o. oder i.v.
•Clarithromycin p.o. oder i.v.
•Clindamycin p.o. oder i.v.
•Daptomycin i.v.
•Ertapenem i.v.
•Flucloxacillin i.v.
•Gentamicin i.v.
•Imipenem i.v.
•Linezolid p.o. und i.v.
•Meropenem i.v.
•Metronidazol p.o. oder i.v.
•Piperacillin/Tazobactam i.v.
- Tigecyclin i.v.
•Tobramycin i.v.
•Trimethoprim/ Sulfamethoxazol (Cotrimoxazol) p.o. und i.v.
•Vancomycin i.v.
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
pregnancy and breastfeeding
instable clinical Situation
use of IMP not according to SmPC
active pneumonia, that is not fully treated on day of inclusion
current acute exacerbation of Asthma bronchiale or COPD
confirmed diagnosis on day of enrolment of congenital or acquired immune deficiency
current immunosuppressive therapy and/or = 3 months prior to enrolment (in case of corticosteroids = 20mg prednisolone/d or equivalent)
current chemotherapy and/or = 3 months prior to enrolment
confirmed diagnosis or high clinical suspicion of hematological malignancy including myelodisplastic syndrome, chronic lymphocytic leukaemia or multiple myeloma
Crohn's disease or ulcerative colitis
confirmed diagnosis of Clostridium difficile Enteritis
confirmed diagnosis on day of enrolment of cystic fibrosis
confirmed diagnosis on day of enrolment of open lung tuberculosis
confirmed diagnosis on day of enrolment of advanced stage lung cancer (stage III/IV)
middle or high risk of bronchoskopy as judged by investigating physician
all contraindications against medication or adjuvants used for analdosedation during bronchoscopy, in detail
against midazolam:
hypersensitivity against midazolam
acute respiratory failure
against propofol:
hypersensitivity against propofol or one of the adjuvants, such as soy allergy
against lidocain:
hypersensitivity against lidocain
shock
acute heart failure
severe uncontrolled cardiac arrythmia
missing consent for storage and transfer of data within the clinical study
participation in another clinical trial within 30 days prior or currently
previous participation in this study
hospitalisation ordered by court
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Main objective of the trial is to study the effect of antibiotic therapies on pulmonary immunoglobulin A (IgA) in mechanically ventilated patients. Based on data from mouse models and a pilot study from our research group, we assume that antibiotic therapies reduce pulmonary IgA level.;Secondary Objective: Secondary objectives of the trial are the investigation of the effect of antibiotic therapies on other immune parameters in lung and serum as well as in saliva and on the respiratory and intestinal microbiota and the incidence of ventilator-associated infections and hospitalisation time.;Primary end point(s): pulmonary IgA as measured in broncheoalveolar lavage fluid (BALF);Timepoint(s) of evaluation of this end point: single measure on day 0-2
- Secondary Outcome Measures
Name Time Method