A Pharmacokinetics Study of Daptomycin in Critically Ill Patients and Effects of Daptomycin on Kidney

Sponsor

Zhongnan Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04277143

Collaborator

(none)

120

Enrollment

Location

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Outcome, Fatal Infection	Drug: Daptomycin

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

The Influence Factors of Pharmacokinetics/Pharmacodynamics of Daptomycin in Severe Patients and the the Effect of Different Blood Concentration of Daptomycin on the Outcomes of Renal Function

Anticipated Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
critical ill patient with bloodstream infections Severe patients with bloodstream infections often have sepsis / septic shock, acute kidney injury (AKI), hypoproteinemia, and renal replacement treatment.	Drug: Daptomycin Adult patients are given the recommended dose of daptomycin for injection. Patients with creatinine clearance (CLCR) ≥ 30 mL / min: 6 mg / kg every 24 hours. Patients with creatinine clearance (CLCR) <30mL / min (including hemodialysis or peritoneal dialysis): 6mg / kg every 48 hours. Dissolve 6mg / kg of this drug in 0.9% sodium chloride injection and instill it over a 30-minute time course once every 24 or 48 hours.

Arm

Intervention/Treatment

critical ill patient with bloodstream infections

Severe patients with bloodstream infections often have sepsis / septic shock, acute kidney injury (AKI), hypoproteinemia, and renal replacement treatment.

Drug: Daptomycin

Adult patients are given the recommended dose of daptomycin for injection. Patients with creatinine clearance (CLCR) ≥ 30 mL / min: 6 mg / kg every 24 hours. Patients with creatinine clearance (CLCR) <30mL / min (including hemodialysis or peritoneal dialysis): 6mg / kg every 48 hours. Dissolve 6mg / kg of this drug in 0.9% sodium chloride injection and instill it over a 30-minute time course once every 24 or 48 hours.

Outcome Measures

Primary Outcome Measures

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
Plasma trough concentration [1 week]
Plasma trough concentration of daptomycin
Area under the plasma concentration versus time curve (AUC) [1 week]
Area under the plasma concentration versus time curve (AUC) of daptomycin
Clearance of daptomycin [1 week]
Daptomycin is metabolized mainly by the kidneys
Half-life [1 week]
Half-life of plasma daptomycin
Protein binding rate [1 week]
Reversible binding of daptomycin to plasma proteins (mainly serum albumin)
Serum creatinine [1 week]
Serum creatinine can reflect kidney function
Urine output [1 week]
Urine volume can reflect kidney function
Blood Urea Nitrogen [1 week]
It can reflect kidney function
Urine protein [1 week]
Reflect kidney function
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
In-hospital mortality [28days]
Reflect patient prognosis
ICU hospital stay length [28 days]
Reflect patient prognosis
Total hospital stay length [28 days]
Reflect patient prognosis

Secondary Outcome Measures

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
C-Reactive Protein [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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

Patients with severe bloodstream infections eligible for daptomycin indications
Treatment in the ICU
Patients aged 18 to 65

Exclusion Criteria:

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