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Sepsis and septic shock patients are considered to have a high risk of complications and death. Appropriate antimicrobial therapy plays an important role in determining outcomes in septic patients. However, pathophysiologic changes associated with critical illness have an impact on pharmacokinetics of antimicrobials. In addition, increasing bacterial resistance is also a growing concern, especially in intensive care units., Consequently, standard antimicrobial dose may not be sufficient to achieve pharmacokinetic/pharmacodynamic target in sepsis and septic shock patients. The purpose of this study is to compare a therapy between meropenem standard dose and meropenem high dose in the treatment of sepsis and septic shock
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Meropenem standard dose | Active Comparator | Meropenem 1 g every 8 hours |
|
| Meropenem high dose | Active Comparator | Meropenem 2 g every 8 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Meropenem standard dose | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| SOFA score change | The Sequential organ failure assessment (SOFA) score describe the time course of multiple organ dysfunction. The SOFA score is composed of scores for six organ systems (respiratory, cardiovascular, neurological, hepatic, renal and coagulation). The function of six organ systems is scored from 0 (no organ dysfunction) to 4 (severe organ dysfunction), and the individual organ scores are then summed to a total score between 0 and 24. Primary outcome is assessing change between SOFA score at baseline and SOFA score at day 4 after treatment by meropenem | Change from Baseline SOFA score at day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | In hospital mortality | 14 and 28 days |
| Clinical cure | Composite of:
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tospon Lertwattanachai, B.sc.(Pharm) | Faculty of Pharmacy, Mahidol University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Faculty of Medicine Ramathibodi Hospital | Ratchathewi | Bangkok | 10400 | Thailand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25753628 | Background | Jaruratanasirikul S, Thengyai S, Wongpoowarak W, Wattanavijitkul T, Tangkitwanitjaroen K, Sukarnjanaset W, Jullangkoon M, Samaeng M. Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units. Antimicrob Agents Chemother. 2015;59(6):2995-3001. doi: 10.1128/AAC.04166-14. Epub 2015 Mar 9. | |
| 28098629 |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| D016638 | Critical Illness |
| D009102 | Multiple Organ Failure |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 |
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| Meropenem high dose | Drug |
|
|
| Day 3, 5, 7, 10 and 14 |
| Microbiological cure | Elimination of the study entry pathogen within 14 days after received meropenem
| Day 3, 5, 7, 10 and 14 |
| Duration of vasopressor agents | Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation | 14 and 28 days |
| Duration of mechanical ventilator | Time interval (day) of mechanical ventilator | 14 and 28 days |
| Length of ICU stay | Time interval (day) from ICU admission (after randomization) to ICU discharge | 14 and 28 days |
| Length of hospital stay | Time interval (day) from hospital admission (after randomization) to hospital discharge | 14 and 28 days |
| %T > MIC | % time of meropenem concentration above MIC | Day 1 |
| Background |
| Roberts JA, Kumar A, Lipman J. Right Dose, Right Now: Customized Drug Dosing in the Critically Ill. Crit Care Med. 2017 Feb;45(2):331-336. doi: 10.1097/CCM.0000000000002210. |
| 27148448 | Background | Suwantarat N, Carroll KC. Epidemiology and molecular characterization of multidrug-resistant Gram-negative bacteria in Southeast Asia. Antimicrob Resist Infect Control. 2016 May 4;5:15. doi: 10.1186/s13756-016-0115-6. eCollection 2016. |
| 25038549 | Background | Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient--concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev. 2014 Nov 20;77:3-11. doi: 10.1016/j.addr.2014.07.006. Epub 2014 Jul 15. |
| 25888181 | Background | Marquet K, Liesenborgs A, Bergs J, Vleugels A, Claes N. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Crit Care. 2015 Feb 16;19(1):63. doi: 10.1186/s13054-015-0795-y. |
| 7648757 | Background | Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995 Apr;28(4):275-86. doi: 10.2165/00003088-199528040-00002. |
| 28231816 | Background | de Grooth HJ, Geenen IL, Girbes AR, Vincent JL, Parienti JJ, Oudemans-van Straaten HM. SOFA and mortality endpoints in randomized controlled trials: a systematic review and meta-regression analysis. Crit Care. 2017 Feb 24;21(1):38. doi: 10.1186/s13054-017-1609-1. |
| 32318268 | Derived | Lertwattanachai T, Montakantikul P, Tangsujaritvijit V, Sanguanwit P, Sueajai J, Auparakkitanon S, Dilokpattanamongkol P. Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial. J Intensive Care. 2020 Apr 15;8:26. doi: 10.1186/s40560-020-00442-7. eCollection 2020. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D020969 | Disease Attributes |
| Amides |
| D009930 | Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |