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

NCT04277143 | Unknown

• 1 other identifier: 2019018
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Outcome, Fatal; Infection

Keywords

daptomycin; pharmacokinetics; pharmacodynamics; critical ill patients; outcome

Outcome Measures

Primary Outcomes (18)

• Apparent volume of distribution

  Apparent volume of distribution of daptomycin in the patient's blood

  1 week

• Peak plasma concentration

  Peak plasma concentration of daptomycin

  1 week

• Plasma trough concentration

  Plasma trough concentration of daptomycin

  1 week

• Area under the plasma concentration versus time curve (AUC)

  Area under the plasma concentration versus time curve (AUC) of daptomycin

  1 week

• Clearance of daptomycin

  Daptomycin is metabolized mainly by the kidneys

  1 week

• Half-life

  Half-life of plasma daptomycin

  1 week

• Protein binding rate

  Reversible binding of daptomycin to plasma proteins (mainly serum albumin)

  1 week

• Serum creatinine

  Serum creatinine can reflect kidney function

  1 week

• Urine output

  Urine volume can reflect kidney function

  1 week

• Blood Urea Nitrogen

  It can reflect kidney function

  1 week

• Urine protein

  Reflect kidney function

  1 week

• Cystatin C

  Reflect kidney function

  1 week

• β2-microglobulin(β2-MG)

  Reflect kidney function

  1 week

• Major Adverse kidney Event（MAKE）

  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.

  28days

• ICU mortality

  Reflect patient prognosis

  28days

• In-hospital mortality

  Reflect patient prognosis

  28days

• ICU hospital stay length

  Reflect patient prognosis

  28 days

• Total hospital stay length

  Reflect patient prognosis

  28 days

Secondary Outcomes (8)

• White blood cell count

  1 week

• Neutrophil ratio

  1 week

• C-Reactive Protein

  1 week

• Procalcitonin

  1 week

• Interleukin-6

  1 week

Study Arms (1)

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

Interventions

Daptomycin DRUG

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.

critical ill patient with bloodstream infections

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to the Department of Critical Medicine, Zhongnan Hospital of Wuhan University , considering bloodstream infections caused by Gram-positive bacteria。

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430000, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Take blood and urine samples at several time points before and after daptomycin administration, and measure the blood and urine concentrations of the patient

MeSH Terms

Conditions

Infections

Interventions

Daptomycin

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Zhiyong Peng, Professor

  Wuhan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiyong Peng, Professor

CONTACT

+8618672396028; pengzy5@hotmail.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor; Chief physician

Study Record Dates

• First Submitted: February 16, 2020
• First Posted: February 20, 2020
• Study Start: December 1, 2020
• Primary Completion: July 31, 2022
• Study Completion: December 31, 2022
• Last Updated: November 13, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)