A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia
- Conditions
- MRSA Bacteremia
- Interventions
- Registration Number
- NCT05225558
- Lead Sponsor
- LigaChem Biosciences, Inc.
- Brief Summary
The objectives of this study is to exploratory whether Vancomycin + Delpazolid is more effective to the standard of treatment (Vancomycin)/ for hospitalized adults with MRSA bacteraemia.
- Detailed Description
The mortality from S aureus bacteremia is higher for MRSA than for methicillin-susceptible S aureus (MSSA), typically at 20% to 25%.
The current standard therapy for MRSA bacteremia is Vancomycin. Vancomycin has many shortcomings, including poor tissue penetration and slow killing time. Vancomycin has reduced efficacy against MRSA and tended to increase the MIC level (called MIC creep). Addition of Delpazolid to Vancomycin could improve the known drawbacks of Vancomycin alone.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 40
- Male or female ≥19 years of age on the date of written consent
- Subject who has confirmed positive MRSA at least one set of blood cultures within 72 hours prior to randomization OR, Subject who has confirmed positive MRSA at least one set of blood culture whthin 96 hours prior to randomization and treated with vancomycin at least 72 hours prior to randomization
- Subject who has clinical symptoms or signs of MRSA bacteremia according to the judgment of the investigator
- Subject who voluntarily decides to participate in this clinical trial after being explained fully, and agrees in writing to implement the clinical trial compliance matters
- Subject with polymicrobial bacteremia or infections including Gram-negative strain
- Subject undergoing or in need of treatment with antiviral or antifungal drugs
- Subject who has received treatment for MRSA bacteremia within 3 months of screening (Subjects who have "re-infection" by investigator's judgement may participant in the study.)
- Subject who has been administered effective antibiotics against MRSA (Vancomycin, etc.) for more than 96 hours prior to the first investigational product administration. (However, antibiotics effective for MRSA such as vancomycin are allowed to be administered for less than 72 hours.)
- Septic shock patients
- Subject who has hypersensitivity to vancomycin or linezolid
- Subject who has a history of hypersensitivity to peptide-based antibiotics and aminoglycoside-based antibiotics
- Subject who is receiving a MAO inhibitor(MAOI) or has received MAOI within 14 days of the first investigational drug administration
- Subject taking serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptan), meperidine, or buspirone
- Subject with severely decreased immunity (Severe neutropenia (ANC <0.5×10^9/L) etc.)
- Subject who is expected to die within 2 days due to serious complications of MRSA bacteremia based on the judgment of the investigator
- Body Mass Index (BMI) ≥35 kg/m2
- Subject who is unable to administer drugs orally
- Pregnant or lactating female, female or male with childbearing potential who disagrees with the use of appropriate contraceptive methods during the study and up to 14 days after the last dose of the investigator product
- Subject who has received other clinical trial drugs within 30 days of screening
- Subject who is not suitable for participation in this clinical trial according to the medical findings of investigators
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination therapy - Vancomycin (IV) plus Delpazolid (PO) Delpazolid Vancomycin: IV infusion per 2020 IDSA guideline * Intravenous Vancomycin dosed as per 2020 IDSA guideline * Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L. * Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin). Delpazolid: 800 mg, BID, PO Monotherapy - Vancomycin (IV) plus Placebo of Delpazolid (PO) Vancomycin Vancomycin: IV infusion per 2020 IDSA guideline * Intravenous Vancomycin dosed as per 2020 IDSA guideline * Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L. * Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin). Placebo of Delpazolid: BID, PO Combination therapy - Vancomycin (IV) plus Delpazolid (PO) Vancomycin Vancomycin: IV infusion per 2020 IDSA guideline * Intravenous Vancomycin dosed as per 2020 IDSA guideline * Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L. * Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin). Delpazolid: 800 mg, BID, PO Monotherapy - Vancomycin (IV) plus Placebo of Delpazolid (PO) Placebo of Delpazolid Vancomycin: IV infusion per 2020 IDSA guideline * Intravenous Vancomycin dosed as per 2020 IDSA guideline * Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion were recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L. * Depending on the investigator's judgment, it was allowed to change to Daptomycin after at least one week of administration of Vancomycin, and also it was allowed to change to oral antibiotics other than oxazolidinones after two weeks of administration of Vancomycin (including Daptomycin). Placebo of Delpazolid: BID, PO
- Primary Outcome Measures
Name Time Method Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_FAS at Day 14 * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'.
* Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100Overall Cure Rate at Day 14 After the Start of Treatment (Composite Response Rate: Clinical Improvement Plus Clearance of Bacteremia)_PPS at Day 14 * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'.
* Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100
- Secondary Outcome Measures
Name Time Method Overall Cure Rate by End of Treatment (EOT)_FAS Day 7 visit and EOT (up to 6 weeks) visit * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'.
* Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100Overall Cure Rate by End of Treatment (EOT)_PPS Day 7 visit and EOT (up to 6 weeks) visit * 'Overall cure' means that there are no symptoms of infection that existed when enrolled in the clinical trial, there are no new metastatic infection due to MRSA and no new infection (clinical improvement), and MRSA negative is confirmed twice in a row as a result of blood culture tests (clearance of bacteremia). If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as 'clearance of bacteremia'.
* Composite Response rate = (number of participants showing overall cure at Day 14/number of participants in each treatment group) x 100Mortality From MRSA Bacteremia by EOT_FAS During the treatment period (from the first administration to EOT (up to 6 weeks)) * Proportion of participants who died due to MRSA bacteremia
* Overall mortality = (number of participants who died/number of participants in each treatment group) x 100Mortality From MRSA Bacteremia by EOT_PPS During the treatment period (from the first administration to EOT (up to 6 weeks)) * Proportion of participants who died due to MRSA bacteremia
* Overall mortality = (number of participants who died/number of participants in each treatment group) x 100Relapse Rate of MRSA bacteremia_FAS from the first administration to TOC (4 weeks after EOT) * Defined as a positive blood culture to MRSA when previous ones were negative
* Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100Relapse Rate of MRSA bacteremia_PPS from the first administration to TOC (4 weeks after EOT) * Defined as a positive blood culture to MRSA when previous ones were negative
* Relapse rate of MRSA bacteremia = (number of participants with Relapse of MRSA bacteremia after clearance of MRSA bacteremia until TOC visit/number of participants with clearance of MRSA bacteremia in each treatment group) x 100Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_FAS Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks) * Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test
* Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100Clearance Rate of MRSA Bacteremia at Day 3, Day 5, Day 7, Day 14, EOT_PPS Day 3, Day 5, Day 7, Day 14, EOT (up to 6 weeks) * Proportion of participants who confirmed MRSA negative two consecutive set in the blood culture test
* Clearance Rate = (number of subjects who achieved clearance at each visit/number of subjects in each treatment group) x 100Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_FAS Day 3, Day 5, Day 7, Day 14 * Proportion of participants who have positive results on blood culture tests
* Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100Persistent Rate of Bacteremia at Day 3, Day 5, Day 7, Day 14_PPS Day 3, Day 5, Day 7, Day 14 * Proportion of participants who have positive results on blood culture tests
* Persistent rate of bacteremia = (number of subjects who showing persistent bacteremia up to each visit /number of subjects in each treatment group up to each visit) x 100Time to Clearance of MRSA bacteremia_FAS by EOT (up to 6 weeks) If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed.
Time to Clearance of MRSA bacteremia_PPS by EOT (up to 6 weeks) If negative in the blood culture test is confirmed for the first time, additional test will be performed the next day, and if it results negative for a total of two times in a row, it is judged as clearance of bacteremia. The period until the clearance of bacteremia is defined as the period (day) from the date of the first blood culture test within 72 hours prior to randomization with MRSA positive (index blood culture) to the date of the blood culture test with the first negative result confirmed.
Trial Locations
- Locations (6)
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Chosun University Hospital
🇰🇷Gwangju, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Korea University Ansan Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of