A Pharmacokinetics Study of Daptomycin in Critically Ill Patients and Effects of Daptomycin on Kidney
- Conditions
- InfectionOutcome, Fatal
- Interventions
- Registration Number
- NCT04277143
- Lead Sponsor
- Zhongnan Hospital
- Brief Summary
Daptomycin ，is the first approved member of a new class of antimicrobials, the cyclic lipopeptides, and presents selective action against gram-positive bacteria, including methicillin- and vancomycin-resistant strains，disrupting the transfer of amino acids in the cell membrane, thus hindering the biosynthesis of bacterial cell cell wall peptide polysaccharide, changing the properties of cytoplasm membrane, can destroy bacterial cell membrane function in many ways, and quickly kill gram-positive bacteria. Because of its unique chemical structure and sterilization mechanism, bacteria rarely develop resistance to daptomycin. Daptomycin can be reversibility combined with human plasma protein (mainly serum albumin) and metabolized mainly through the kidneys.
There is still a lot of controversy about the application of daptomycin in patients with severe illness. Although studies suggest that daptomycin has less damage to kidney function than vancomycin, the effect of daptomycin on kidney function in severely ill patients is not yet clear, and more clinical studies are needed to explore their relationship. In addition, it is not clear whether the physiological pathology of specific populations such as sepsis/infectious shock, acute kidney injury, (AKI), hypoproteinemia, and renal replacement treatment affects the pharmacokinetics/pharmacodynamics of Daptomycin.
By exploring the application of daptomycin in patients with severe illness, this study explores the effects of special pathological physiological states such as sepsis/infectious shock and hypoproteinemia on daptomycin PK/PD, as well as the effects of different hemoglobin concentrations of daptomycin on the outcome of kidney function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
- Patients with severe bloodstream infections eligible for daptomycin indications
- Treatment in the ICU
- Patients aged 18 to 65
- Pregnant and lactating women
- The patient or his agent refused to participate in the trial
- Incomplete clinical medical information
- Patient participates in another clinical trial at the same time
- Previous history of myopathy or current CPK increase more than 2 times than normal
- Patients need to use warfarin anticoagulation
- Patients use tobramycin for anti-infection
- Patients use drugs such as cyclosporine and fibrates that can cause adverse reactions to muscle disease
- Patients with Gram-negative bacterial infections caused by abdominal and respiratory infections
- Patients with heart failure, respiratory failure, Glasgow coma index (GCS) ≤ 8 points, liver function CHILD PUGH score C that are not related to the infection
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description critical ill patient with bloodstream infections Daptomycin Severe patients with bloodstream infections often have sepsis / septic shock, acute kidney injury (AKI), hypoproteinemia, and renal replacement treatment.
- Primary Outcome Measures
Name Time Method Area under the plasma concentration versus time curve (AUC) 1 week Area under the plasma concentration versus time curve (AUC) of daptomycin
Blood Urea Nitrogen 1 week It can reflect kidney function
Urine protein 1 week Reflect kidney function
Serum creatinine 1 week Serum creatinine can reflect kidney function
Apparent volume of distribution 1 week Apparent volume of distribution of daptomycin in the patient's blood
Peak plasma concentration 1 week Peak plasma concentration of daptomycin
Half-life 1 week Half-life of plasma daptomycin
Protein binding rate 1 week Reversible binding of daptomycin to plasma proteins (mainly serum albumin)
Urine output 1 week Urine volume can reflect kidney function
Plasma trough concentration 1 week Plasma trough concentration of daptomycin
Cystatin C 1 week Reflect kidney function
β2-microglobulin(β2-MG) 1 week Reflect kidney function
Major Adverse kidney Event（MAKE） 28days Major Adverse kidney Event（MAKE）Refers to death, need for renal replacement therapy, and creatinine levels that are twice or more the baseline value；It can reflects the outcome of renal function.
ICU mortality 28days Reflect patient prognosis
ICU hospital stay length 28 days Reflect patient prognosis
Total hospital stay length 28 days Reflect patient prognosis
Clearance of daptomycin 1 week Daptomycin is metabolized mainly by the kidneys
In-hospital mortality 28days Reflect patient prognosis
- Secondary Outcome Measures
Name Time Method Bacterial culture results 1 week Reflect the severity of the patient's infection
Body temperature 1 week Reflect the severity of the patient's infection
Vascular drug use days 1 week Assess patients' systemic circulation
C-Reactive Protein 1 week Reflect the severity of the patient's infection
White blood cell count 1 week Reflect the severity of the patient's infection
Neutrophil ratio 1 week Reflect the severity of the patient's infection
Procalcitonin 1 week Reflect the severity of the patient's infection
Interleukin-6 1 week Reflect the severity of the patient's infection
Trial Locations
- Locations (1)
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China