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ID
Source
Brief title
Health condition
Community Acquired Pneumonia
Rifampicin
Lipoteichoid Acid
Pneumolysin
inflammatory respons
clinical outcome
prognosis
pneumonia
Emergency medicine
hospital
Spoedeisende hulp
ziekenhuis
Thuis opgelopen longontsteking
CURB-65 score
rifampicine
lipoteichoidzuur
pneumolysine
inflammatoire respons
prognose
klinische uitkomst
pneumonie
Sponsors and support
LUMC
Intervention
Outcome measures
Primary outcome
To primary objective is to demonstrate a reduction in lipoteichoic acid release in
patients with pneumococcal pneumonia treated with rifampicin and standard
treatment as compared to those given standard treatment only. Lipoteichoic acid
release will be quantified by measuring lipoteichoic acid in serum and urine.
Evaluable patients for Intention-to-Treat analysis are those who met the following
criteria: (1) enrollment criteria of pneumonia, with 2 or more points in the
CURB65 score, for which a patient is admitted to the hospital, (2) Streptococcus
pneumonia is identified as the cause of pneumonia, (3) received at least one
dose of study drugs and (4) outcome is measured at 30 days.
Evaluable patients for Per-Protocol analysis are those who meet the following
criteria: (1) enrollment criteria of pneumonia, with 2 or more points in the
CURB65 score, for which a patient is admitted to the hospital, (2) Streptococcus
pneumonia is identified as the cause of pneumonia, (3) received the study drug
for 48 hours and (4) outcome is measured at 30 days.
Secondary outcome
The secondary objectives of this study are to determine:
1. Duration of symptoms;
2. Length of hospital stay;
3. 30 Day all cause mortality;
4. Length of ICU stay;
5. (Multiple) organ failure on ICU;
6. Adverse events;
7. Serum biomarkers: C-reactive protein (CRP), Procalcitonin (PCT), Plasma
secretory leukocyte protease inhibitor (SLPI), Soluble triggering receptor
expressed on myeloid cells (sTREM)-1, IP-10, vitamin D and antimicrobial
peptides like Cathelicidin and Beta-defensin-2, lipopolysaccharide;
8. Microbiological diagnosis;
9. Evaluation of empirical coverage of the microbiological diagnosis (with
this, we can determine whether the empirical treatment was appropriate or
not);
10. Emerging of resistant microorganism carriage.
Background summary
N/A
Study objective
In vitro studies have shown that – in the presence of identical bacterial kill –
rifampicin causes reduced release of proinflammatory components of
Streptococcus pneumoniae cell wall, lipoteichoic acid (LTA), as compared with
other antibiotics including benzylpenicillin. Because the inflammatory response to
these proinflammatory components determines the intensity of the host immune
reaction and, by consequence, collateral tissue damage in infection, a reduced
inflammatory response in pneumococcal infection, e.g., community acquired
pneumonia, may reduce damage to the lungs and severity of disease in
pneumonia.
We will try to demonstrate a reduction in lipoteichoic acid release in
patients with pneumococcal pneumonia treated with rifampicin and standard
treatment as compared to those given standard treatment only.
Study design
Assessments of clinical response will be performed continuously during the
treatment period by the attending physician, 1-3 days after admission by the
clinical researchers, 30 days after start of therapy by a visit of the clinical
researchers and 90 days post therapy by a telephone call.
Besides normal diagnostic procedures (sputum culture, blood culture, routine
laboratory tests), extra samples are taken:
1. At inclusion: 1 throat swabs, 1 rectum swabs, a urine sample and 4 ml of
EDTA blood for biomarker assay and 4 ml of Natriumheparin blood for LTA measurement and 2 ml of blood
(in PAXgene RNA tubes);
2. At 2, 4, 8, 16, 24 and 48 hours after inclusion: 8 ml of blood and a urine
sample (10ml); at 24 hours we'll also collect 2ml of blood in PAXgene tubes;
3. At day 30: 10 ml of blood, a urine sample (10 ml) and a rectum swab.
Intervention
After informed consent, patients will be randomized (2:1) on the emergency
department.
The intervention group (2/3) receives rifampicin 600 mg b.i.d. in the first 48 hours + a beta-lactam antibiotic (mostly penicillin) with or without ciprofloxacin.
The control group (1/3) receives a beta-lactam antibiotic (mostly penicillin) with or without ciprofloxacin.
The choice whether or not to add ciprofloxacin is described in the Dutch SWAB guidelines (http://www.swab.nl/richtlijnen).
LUMC<br>
Albinusdreef 2<br>
Postbus 9600
G.H. Groeneveld
Leiden 2300 RC
The Netherlands
g.h.groeneveld@lumc.nl
LUMC<br>
Albinusdreef 2<br>
Postbus 9600
G.H. Groeneveld
Leiden 2300 RC
The Netherlands
g.h.groeneveld@lumc.nl
Inclusion criteria
1. Patient aged 18 years or above;
2. Hospitalization for community acquired pneumonia with CURB65 score ≥ 2.
Exclusion criteria
1. Known allergy to rifampicin or other rifamycins;
2. Haemolytic anaemia or thrombopenia as side effect of rifampicin in medical history;
3. Liver failure;
4. Use of voriconazol or protease inhibitors.
Note: Patients using other drugs that influence cytochrome P450 3A4 are not excluded. This is an open label trial, all doctors are aware when their patient is treated with rifampicin (or not). If necessary, proper adjustments of concomitant medications can be
made (e.g. with oral anticoagulants, ciclosporin). A short period of lower levels of drugs that are prescribed for long-term effects (e.g. antihypertensive drugs or glucose lower medication) will not
interfere with long term outcome. In case female patients in reproductive age use oral anticontraceptives, other contraceptive
measures will be advised after discharge from hospital.
Treatment with rifampicin is for maximum of 48 hours. The enzyme
inducing effect is only limited.
The College ter Beoordeling van Geneesmiddelen indicates only
voriconazol and protease inhibitors as a real contra-indication.
5. Female patients who are pregnant
Design
Recruitment
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL3586 |
| NTR-old | NTR3751 |
| CCMO | NL40521.058.12 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |
| OMON | NL-OMON39089 |