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

Infection Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04277143
• Other study ID #: 2019018
• Status: Not yet recruiting
• Start date: December 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: November 2020
• Source: Zhongnan Hospital
• Contact: Zhiyong Peng, Professor
• Phone: +8618672396028
• Email: pengzy5[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 31, 2022
• Est. primary completion date: July 31, 2022
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Infection
• Outcome, Fatal

Intervention

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.

Locations

Country	Name	City	State
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Zhongnan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apparent volume of distribution	Apparent volume of distribution of daptomycin in the patient's blood	1 week
Primary	Peak plasma concentration	Peak plasma concentration of daptomycin	1 week
Primary	Plasma trough concentration	Plasma trough concentration of daptomycin	1 week
Primary	Area under the plasma concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC) of daptomycin	1 week
Primary	Clearance of daptomycin	Daptomycin is metabolized mainly by the kidneys	1 week
Primary	Half-life	Half-life of plasma daptomycin	1 week
Primary	Protein binding rate	Reversible binding of daptomycin to plasma proteins (mainly serum albumin)	1 week
Primary	Serum creatinine	Serum creatinine can reflect kidney function	1 week
Primary	Urine output	Urine volume can reflect kidney function	1 week
Primary	Blood Urea Nitrogen	It can reflect kidney function	1 week
Primary	Urine protein	Reflect kidney function	1 week
Primary	Cystatin C	Reflect kidney function	1 week
Primary	ß2-microglobulin(ß2-MG)	Reflect kidney function	1 week
Primary	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
Primary	ICU mortality	Reflect patient prognosis	28days
Primary	In-hospital mortality	Reflect patient prognosis	28days
Primary	ICU hospital stay length	Reflect patient prognosis	28 days
Primary	Total hospital stay length	Reflect patient prognosis	28 days
Secondary	White blood cell count	Reflect the severity of the patient's infection	1 week
Secondary	Neutrophil ratio	Reflect the severity of the patient's infection	1 week
Secondary	C-Reactive Protein	Reflect the severity of the patient's infection	1 week
Secondary	Procalcitonin	Reflect the severity of the patient's infection	1 week
Secondary	Interleukin-6	Reflect the severity of the patient's infection	1 week
Secondary	Bacterial culture results	Reflect the severity of the patient's infection	1 week
Secondary	Body temperature	Reflect the severity of the patient's infection	1 week
Secondary	Vascular drug use days	Assess patients' systemic circulation	1 week