Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT05024565 |
Other study ID # |
Wang Hao |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
September 20, 2021 |
Est. completion date |
September 1, 2023 |
Study information
Verified date |
August 2021 |
Source |
Qilu Hospital of Shandong University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The prolonged β-lactam Antibiotics intravenous infusion strategy has emerged as the standard
treatment for sepsis despite its unknown efficacy. The investigators will conduct a
prospective, multi-center, cluster randomized controlled clinical trial. The investigators
aimed to compare the clinical efficacy and prognosis of prolonged β-lactam antibiotics
intravenous infusion versus short-term intravenous infusion in ICU patients with early
sepsis. The investigators expect to recruit 40 branch centers and enroll at least 2600
patients with sepsis.
Description:
Sepsis and septic shock can lead to high morbidity and mortality. The mortality of sepsis is
related to inappropriate antibiotic treatment strategy. Due to the pathophysiological
characteristics of patients with sepsis, the pharmacokinetics of antibiotics have changed,
and antibiotic treatment strategies applied to general mild and severe infections may not be
suitable for those patients. The relevant international guidelines recommend that antibiotic
treatment for patients with sepsis should base on pharmacokinetic/pharmacodynamic principles,
but this recommendation is based on low-level clinical evidence.
β-lactam antibiotics, including penicillins, cephalosporins, carbapenems and so on, are the
most widely used antibacterial drugs in clinical practice. The best predictive parameter of
those antibiotic bactericidal activity is the time during which the free drug concentration
exceeds the target microbial MIC value (fT >MIC). According to Monte Carlo approach and
clinical studies, as a PK/PD target value, an effective bactericidal effect can be achieved
if fT>MIC reaches more than 40%; fT>MIC reaches more than 60%-70% can achieve the maximum
bactericidal effect, which can be used in the treatment of severe cases. For severe infection
and prevention of bacterial resistance, fT>MIC needs to reach 90%-100%.
The results of clinical studies have proved that improper or inadequate initial empiric
antibiotic treatment is an independent risk factor that affects the therapeutic effectiveness
and prognosis of severe infections. Important reasons for the lower-than-expected antibiotic
treatment effect in severely ill patients include at least the following two factors: (1)
Changes in the pathophysiological state of severely ill patients on drug metabolism, such as
capillary leakage leading to increased drug distribution volume. As well as the high
excretion and low obstruction hemodynamic characteristics of sepsis, increased renal blood
flow leads to high excretion of water-soluble drugs, which often reduces the effective plasma
concentration of the drug; (2) ICU infection of pathogenic bacteria has increased drug
resistance and increased MIC. The above factors lead to the decrease of drug fT>MIC, which
affects the efficacy of antibiotics. In recent years, the optimization of PK/PD-guided
time-dependent antimicrobial treatment programs have confirmed that the administration method
of prolonging the infusion time or continuous infusion can maintain a good steady-state blood
drug concentration, prolong fT> MIC, and improve clinical curative effect, and can reduce the
amount of antibiotics.
The main problems with PK/PD-guided antimicrobial therapy are: (1) Lack of convincing large
sample clinical research results; (2) It has not been confirmed which subgroup (such as the
sepsis severity, drug-resistant patterns of pathogens, immunocompetence) can be benefited
from this strategy; (3) It is not clear whether the method of prolonged infusion can be
applied in all kinds of β-lactam antibiotics .
This study adopts multi-center, openness, cluster randomization method to group, and
eliminates the bias caused by factors such as the treatment environment in a single ward
through the multi-center study; through Uniform training realizes the standardization of drug
delivery methods to eliminate researchers' human bias in treatment operations and
observations. At the same time, the regional randomization method sets the drug delivery
method for a certain research center in a certain research phase to be determined, which
eliminates the operational error and observation bias when the researcher needs to face
multiple drug delivery programs at the same time. It can greatly reduce research costs and
human bias, and more reliably obtain the impact of PK/PD-guided antibiotic treatment on the
prognosis of patients and the impact of bacterial resistance in the entire ward.