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Rifampicine vermindert de ontstekingsreactie bij patienten met een (matig) ernstige longontsteking.


- candidate number14097
- NTR NumberNTR3751
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR14-dec-2012
- Secondary IDsNL40521.058.12 / 2012-003067-22; CCMO / EudraCT
- Public TitleRifampicine vermindert de ontstekingsreactie bij patienten met een (matig) ernstige longontsteking.
- Scientific TitlePneumonia treated with RIfampicin aTtenuates INflammation.
- ACRONYMPRISTINE
- hypothesisIn 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.
- Healt Condition(s) or Problem(s) studiedEmergency department, Rifampicine, Prognosis, Pneumonia, Pneumolysin, Lipoteichoid Acid, Inflammatory respons, Clinical outcome
- Inclusion criteria1. Patient aged 18 years or above;
2. Hospitalization for community acquired pneumonia with CURB65 score ≥ 2.
- Exclusion criteria1. 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
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingNone
- controlActive
- groupParallel
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 7-jan-2013
- planned closingdate7-jan-2014
- Target number of participants40
- InterventionsAfter 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).
- Primary outcomeTo 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 outcomeThe 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.
- TimepointsAssessments 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.
- Trial web siteN/A
- statusplanned
- CONTACT FOR PUBLIC QUERIES G.H. Groeneveld
- CONTACT for SCIENTIFIC QUERIESProf. dr. J.T. Dissel, van
- Sponsor/Initiator Leiden University Medical Center (LUMC)
- Funding
(Source(s) of Monetary or Material Support)
Virgo consortium, Netherlands Genomics Initiative (NGI)
- PublicationsN/A
- Brief summaryN/A
- Main changes (audit trail)
- RECORD14-dec-2012 - 4-jan-2013


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