Sepsis, Sepsis - to Reduce Mortality in the Intensive Care Unit, Septic Shock
Conditions
Keywords
sepsis, intensive care, critically ill, antibiotic, septic shock
Brief summary
The aim of this study is to investigate if an initial short double dose of beta-lactam antibiotics will reduce mortality in critically ill patients with sepsis.
Detailed description
Objective To determine if using higher dosages of beta-lactam antibiotics in the initial phase of sepsis improves clinical outcome of critically ill patients. Main trial endpoints The main trial endpoint is all cause 28-day mortality. Secondary trial endpoints Secondary trial endpoints include: Hospital length of stay, ICU length of stay, microbiological eradication, time to shock reversal, clinical cure, Δ Lactate, Δ PCT, Δ SOFA, 90- day mortality, 365-day mortality, pharmacodynamic target, post study calculation of the costs in both study, groups, EQ5D questionnaire 3 and 12 months after Admission, iMTA productivity questionnaire 3 and 12 months after admission, iMTA medical consumption questionnaire 3 and 12 months after admission and the number of adverse events. Trial design This is an open label, randomized controlled trial. Trial population The trial population will consist of adult patients admitted to the intensive care department with sepsis who will be treated according to protocol with beta-lactam antibiotics. Interventions During the trial participants in the intervention group will receive a double dose of antibiotics for the first 48 hours in comparison to the standard dose in the control group.
Interventions
DRUGDouble dosing of beta-lactam antibiotic
This arm will receive double dosing of beta-lactam antibiotics for the first 48 hours after inclusion.
Sponsors
Maasstad Hospital
Albert Schweitzer Hospital
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age * Receiving intravenous antibiotic therapy of the target drugs (including continuous infusion of beta-lactam antibiotics) * Primary infection * Admitted to the ICU * Meeting the Sepsis-3 criteria for septic shock: sepsis in addition to shock requiring the start of vasopressors to maintain a mean arterial pressure 65 mmHg or greater, and a serum lac tate level greater than 2.0 mmol/L following adequate fluid resuscitation.
Exclusion criteria
* Patient or legal representative not available to give informed consent within 72 hours after admittance * Pregnancy * Admittance for burn wounds * Patients receiving target antibiotics only as prophylaxis within the context of Selective Diges tive tract Decontamination (SDD) * Enrolment in another interventional trial * Patient received the study antibiotic for more than 24 hours before inclusion * Patient receiving extracorporeal membrane oxygenation (ECMO) * Patient is already treated with a double dose of antibiotics based on suspected infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28-day mortality | From enrollment to 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 365-day mortality | From enrollment to the 365 days | — |
| ICU lengt of stay | From enrollment to the end of the study period at 12 months | — |
| Hospital lengt of stay | From enrollment to the end of the study period at 12 months | — |
| Time to shock reversal | From enrollment to the end of the study period at 12 months | From enrollment to the use of \<0.1 gamma of vasopressors for 4 consecutive hours. |
| Microbiological eradication | From enrollment to hospital discharge | Eradication of the causative organism from the primary source up to 30 days after therapy when confirmed by at least one repeated culture. In cases where there were no repeat cultures and the patient had resolution of the infection, microbial eradication will be presumed. |
| Clinical cure | From enrollment to 14 days | Completion of β-lactam antibiotic by day 14 without recommencement of antibiotics within 48hrs of cessation for same infective episode (investigator assessment of clinical response) |
| 90-day mortality | From enrollment to 90 days | — |
| Delta SOFA | From enrollment to day 3 | SOFA at day 3 - SOFA at admission |
| Delta Lactate | From enrollment to day 3 | Lactate at day 3 - lactate upon inclusion |
| Quality of life | 3 and 12 months after inclusion | EQ-5D-5L, a quetionnaire scoring 1 to 5 points on 5 domains. A higher score means a worse outcome. |
| Medical consumption | 3 and 12 months after inclusion | iMTA Medical Consumption questionnaire |
| Productivity | 3 and 12 months after inclusion | iMTA Productivity questionnaire |
| Adverse events and toxicity | From enrollment until the end of the study period at 12 months | — |
| Plasma concentrations of the beta-lactam antibiotics | From enrollment to day 3 | Through concentrations take once a day for 3 consectutive days after enrollment. Target attianment is defined as 100%fT\>4xMIC |
Countries
Netherlands
Contacts
Primary ContactBirgit C.P. Koch, PharmD
Outcome results
None listed