Right Dose, Right Now|
|- candidate number||27792|
|- NTR Number||NTR6689|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-aug-2017|
|- Secondary IDs||ABR: NL61682.029.17 METc VUmc|
|- Public Title||Right Dose, Right Now|
|- Scientific Title||Right Dose, Right Now: Randomized Clinical Trial|
|- hypothesis||Sepsis is a major and growing problem. In the Netherlands alone, around 15.000 patients are diagnosed with severe sepsis each year. Despite major scientific efforts, including many failed clinical trials mainly focusing on inflammatory mediators and the introduction of care bundles, the mortality rate for severe sepsis still remains unacceptably high at around 30%.|
This is alarming, especially since the incidence of sepsis continues to increase and now exceeds that of colon cancer, breast cancer and AIDS combined.
Antibiotics are essential for treating sepsis. Their early and appropriate use has repetitively been shown to reduce mortality rates. However, achieving adequate antibiotic exposure in critically ill patients is a major challenge due to markedly different pharmacokinetic (PK) profiles in the critically ill. Nevertheless, doctors still rely on standard antibiotic dosing schemes, that were developed based on data from healthy volunteers and non-critically ill patients. Depending on patient characteristics, clinical course and therapy, this strategy may result in underdosing and/or drug-related toxicity during the course of intensive care treatment.
Therefore, we developed AutoKinetics (AutoK) software. AutoK aims to make use of patient data that is available from the electronic patient records, for example about fluid balance and renal function. Using this data, AutoK is able to give fast and precise dosing advice, using published pharmacokinetic models of any drug. AutoK runs on the computer at the bedside. Thus, advice is readily available, even before treatment is started, and is continuously updated as disease and therapy evolve: true personalized dosing.
We hypothesize that AutoK can improve antibiotic dosing, morbidity and mortality for severe sepsis.
|- Healt Condition(s) or Problem(s) studied||Sepsis, Infectious diseases, Antibiotics, Pharmacokinetics, Farmacometrics|
|- Inclusion criteria||In order to be eligible to participate in this study, a subject must meet all of the following criteria:|
- Age >18 years
- Suspected or confirmed infection
- Treatment or planned treatment with one or more of the following antibiotics: vancomycin, ceftriaxone, meropenem, ciprofloxacine, cefotaxime.
|- Exclusion criteria||none|
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-okt-2017|
|- planned closingdate||31-dec-2019|
|- Target number of participants||420|
|- Interventions||Patients will be randomized to one of two groups.|
Group 1 (Control group): standard intravenous antibiotic therapy based on current clinical guidelines and practice. Standard therapy will include TDM for vancomycin, but not for the beta-lactams and ciprofloxacin. The standard antibiotic dosing schemes are:
- Vancomycin: continuous infusion 1000 mg/24h
- Ciprofloxacin: 2 x 400mg
- Cefotaxim: 4 x 1000mg
- Meropenem: 3 x 1000mg
- Vancomycin: 1 x 1000 mg
- Ciprofloxacin: 3 x 400 mg
- Ceftriaxon: 1 x 2000 mg
- Meropenem: 3 x 1000 mg
Local standard protocols allow for higher dosing in case of suspicion of atypical pneumonia, central nervous system infection or endocarditis.
Group 2 (Experimental group): Personalized antibiotics dosing guided by AutoK, based on PK models combined with patient data from the electronic patient record. Initial model choice will be determined by the investigators using data from both hospitals (see previously approved protocol – Right Dose, Right Now – Model Validatation – 2017.152) and will be updated when appropriate.
|- Primary outcome||PK target attainment in the first 24-hours. Targets are 100%-fT>4MIC for the beta-lactam antibiotics, fAUC/ MIC>400 for vancomycin and fAUC/MIC ≥125 for ciprofloxacin|
|- Secondary outcome||Time to PK target level, PK target attainment during therapy, attainment of clinical cure, length of ICU and hospital stay, delta Sequential Organ Failure Assessment (SOFA) score at 96 hours, days free of ventilator / hemofiltration / other organ support, ICU / hospital / 28 day / 6-month mortality, quality of life at hospital discharge (EQ-5D-5L) and after 6 months, societal costs (iMTA MCQ and iMTA PCQ on admission versus after 6 months), days free of delirium.
|- Timepoints||- PK target attainment in the first 24-hours.|
- delta Sequential Organ Failure Assessment (SOFA) score at 96 hours
- mortality at 28-days and 6 months
- quality of life at hospital discharge and after 6 months
- societal costs: measurement at admission and after 6 months
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES|| B. van Dijk|
|- CONTACT for SCIENTIFIC QUERIES|| B. van Dijk|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|- Brief summary|
|- Main changes (audit trail)|
|- RECORD||25-aug-2017 - 21-sep-2017|
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