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

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

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.

Study Overview

• Status: Unknown
• Conditions: Infection; Outcome, Fatal
• Intervention / Treatment: Drug: Daptomycin

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Zhiyong Peng, Professor; Phone Number: +8618672396028; Email: pengzy5@hotmail.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Zhongnan Hospital of Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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。

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Pregnant and lactating women
2. The patient or his agent refused to participate in the trial
3. Incomplete clinical medical information
4. Patient participates in another clinical trial at the same time
5. Previous history of myopathy or current CPK increase more than 2 times than normal
6. Patients need to use warfarin anticoagulation
7. Patients use tobramycin for anti-infection
8. Patients use drugs such as cyclosporine and fibrates that can cause adverse reactions to muscle disease
9. Patients with Gram-negative bacterial infections caused by abdominal and respiratory infections
10. 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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
White blood cell count	Reflect the severity of the patient's infection	1 week
Neutrophil ratio	Reflect the severity of the patient's infection	1 week
C-Reactive Protein	Reflect the severity of the patient's infection	1 week
Procalcitonin	Reflect the severity of the patient's infection	1 week
Interleukin-6	Reflect the severity of the patient's infection	1 week
Bacterial culture results	Reflect the severity of the patient's infection	1 week
Body temperature	Reflect the severity of the patient's infection	1 week
Vascular drug use days	Assess patients' systemic circulation	1 week

Collaborators and Investigators

• Sponsor: Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2020
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: February 16, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (ACTUAL): February 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; outcome; pharmacodynamics; daptomycin; critical ill patients
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 2019018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No