Daptomycin vs. Vancomycin for Staph Bacteremia

(DAPTO-SNAP Trial)

Recruiting at 1 trial location

Overseen By Lina Petrella

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Todd C. Lee MD MPH FIDSA

Disqualifiers: Severe allergy, MRSA pneumonia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open label randomized controlled trial for patients with methicillin resistant S. aureus (MRSA) bloodstream infection which will directly compare the two most commonly used therapies, vancomycin and daptomycin. This study is an approved sub-study of The Staphylococcus aureus Network Adaptive Platform (SNAP) trial (NCT05137119)

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Daptomycin for treating Staph bacteremia?

Research shows that Daptomycin is more effective than Vancomycin for treating bloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA) with high vancomycin resistance, as it is associated with lower mortality and higher treatment success rates. ^{1 2 3 4 5}

Is daptomycin safe compared to vancomycin for treating bacterial infections?

Daptomycin and vancomycin are both used to treat serious bacterial infections, but vancomycin can be harmful to the kidneys. Daptomycin is considered a safer alternative, especially for patients with kidney issues. ^{1 5 6 7 8}

How does the drug Daptomycin differ from Vancomycin for treating Staph bacteremia?

Daptomycin is a newer antibiotic that can be used as an alternative to Vancomycin, especially when the bacteria show reduced sensitivity to Vancomycin. It is particularly useful for patients with kidney issues, as Vancomycin can be toxic to the kidneys, and for treating infections with high Vancomycin minimum inhibitory concentrations. ^{1 3 5 9 10}

Research Team

Todd C Lee, MD MPH FIDSA

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Eligibility Criteria

This trial is for patients with a serious blood infection caused by a bacteria called methicillin-resistant Staphylococcus aureus (MRSA). It's open to those who haven't been treated yet. Specific eligibility details are not provided, but typically participants need to meet certain health standards.

Inclusion Criteria

I have a blood infection caused by MRSA.

Exclusion Criteria

I have or might have pneumonia caused by MRSA.

Severe allergy or non-severe rash to vancomycin or daptomycin

My infection is resistant to common antibiotics.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either daptomycin or vancomycin for the treatment of MRSA bacteremia

6 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• Daptomycin
• Vancomycin

Trial Overview The study compares two drugs: Daptomycin and Vancomycin, both given through injection. It aims to find out which one is better at treating MRSA bloodstream infections. Patients will be randomly assigned to receive one of the treatments.

Participant Groups

Group I: Daptomycin Experimental Treatment 1 Intervention

Daptomycin given by injection at a dose determined by the treating clinicians but no less than 6mg/kg

Group II: Vancomycin Active Control 1 Intervention

Vancomycin given by injection at a dose determined by the treating clinicians to achieve a trough-based or AUC-based target

Daptomycin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cubicin for:

• Complicated skin and soft tissue infections
• Right-sided infective endocarditis
• Bacteraemia associated with complicated skin and soft tissue infections or right-sided infective endocarditis

Approved in United States as Cubicin for:

• Complicated skin and skin structure infections caused by susceptible strains of certain Gram-positive microorganisms
• Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis

Approved in Canada as Cubicin for:

• Complicated skin and soft tissue infections caused by susceptible strains of certain Gram-positive microorganisms
• Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis

Approved in Japan as Cubicin for:

• Severe infectious diseases (sepsis, meningitis, osteomyelitis, septic arthritis, etc.) caused by methicillin-resistant Staphylococcus aureus (MRSA)

Who Is Running the Clinical Trial?

Todd C. Lee MD MPH FIDSA

Lead Sponsor

Trials

3

Recruited

660+

The Peter Doherty Institute for Infection and Immunity

Collaborator

Trials

18

Recruited

15,300+

University of Melbourne

Collaborator

Trials

193

Recruited

1,287,000+

Findings from Research

This study is a multicenter, open-label, phase IIB pilot randomized controlled trial designed to compare the efficacy of daptomycin versus vancomycin in treating bloodstream infections caused by methicillin-resistant Staphylococcus aureus with high vancomycin minimum inhibitory concentrations (≥1.5 ug/ml), involving 50 participants over two years.

The primary goal is to assess the impact of these treatments on 60-day all-cause mortality, which could provide crucial insights for clinicians regarding the optimal management of these serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial. Kalimuddin, S., Phillips, R., Gandhi, M., et al.[2021]

In a study of 522 patients with skin and skin-structure infections (SSSIs), daptomycin showed an overall cure rate of 53% for complicated infections and 66% for uncomplicated infections, indicating its efficacy against these types of infections.

The study found that daptomycin was commonly used in conjunction with other antibiotics (42% of cases), and the median treatment duration was longer for complicated infections (14 days) compared to uncomplicated ones (10 days), highlighting the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing clinical experience in patients with skin and skin-structure infections treated with daptomycin. Owens, RC., Lamp, KC., Friedrich, LV., et al.[2013]

In a study of 170 patients with MRSA bacteremia, daptomycin treatment resulted in significantly lower rates of end-of-therapy failure (11% vs 24% for vancomycin) and acute kidney injury (9% vs 23% for vancomycin), suggesting it may be a safer option for patients.

Daptomycin also showed better day 4 bacteremia clearance rates in immunocompromised patients (94% vs 56% for vancomycin), indicating its potential efficacy in this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation. Moise, PA., Culshaw, DL., Wong-Beringer, A., et al.[2018]

Daptomycin significantly reduces mortality and increases treatment success rates compared to vancomycin in adult patients with MRSA bacteremia, based on a systematic review of seven studies involving 907 patients.

For patients with intermediate-risk sources of infection, daptomycin shows a particularly strong advantage, suggesting it should be prioritized for treating MRSA bacteremia when vancomycin is less effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Daptomycin versus Vancomycin for Bacteremia Caused by Methicillin-Resistant Staphylococcus aureus with Vancomycin Minimum Inhibitory Concentration > 1 µg/mL: A Systematic Review and Meta-Analysis Samura, M., Kitahiro, Y., Tashiro, S., et al.[2023]

Daptomycin is recommended as an effective alternative to vancomycin for treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, especially in patients with renal dysfunction or when vancomycin is ineffective due to high minimum inhibitory concentration (MIC) levels.

In critically ill patients with suspected Gram-positive bacteremia, daptomycin is advised as the first-choice treatment, with a recommended dosage of over 6 mg/kg/day to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Daptomycin therapy in patients with bacteremia]. Llinares, P., Iribarren, JA.[2013]

In a study of 159 patients with methicillin-resistant Staphylococcus aureus bacteremia, previous vancomycin therapy did not negatively impact the success rates of subsequent daptomycin treatment, which were high at 81%.

Success rates for daptomycin were consistent across different durations of prior vancomycin exposure, with rates of 89% for 1-3 days, 83% for 4-6 days, and 88% for 7 days or more, indicating that daptomycin remains effective regardless of prior vancomycin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of prior vancomycin therapy and subsequent daptomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteremia. Culshaw, D., Lamp, KC., Yoon, MJ., et al.[2015]

Daptomycin and vancomycin are less effective against slow-growing Staphylococcus epidermidis small-colony variants (SCVs), with vancomycin showing a 7.7-fold decrease in maximal killing effect compared to the parental strain.

The study utilized a site-directed hemB mutant of S. epidermidis to evaluate the pharmacodynamics of these antibiotics, revealing that daptomycin's effectiveness also decreased by 1.5-fold against the SCV mutant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin and daptomycin pharmacodynamics differ against a site-directed Staphylococcus epidermidis mutant displaying the small-colony-variant phenotype. Wu, M., von Eiff, C., Al Laham, N., et al.[2021]

Patients treated with daptomycin experienced 60% fewer antimicrobial adverse events compared to those treated with vancomycin, indicating a safer profile for daptomycin in outpatient settings.

Daptomycin also required 80% fewer antimicrobial interventions than vancomycin, suggesting it may lead to lower healthcare utilization while maintaining similar readmission rates for complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events, healthcare interventions and healthcare utilization during home infusion therapy with daptomycin and vancomycin: a propensity score-matched cohort study. Shrestha, NK., Mason, P., Gordon, SM., et al.[2022]

Vancomycin and daptomycin are effective initial treatments for patients with MRSA bacteremia, which is an infection caused by a resistant strain of Staphylococcus aureus.

For cases of persistent MRSA bacteremia or infections caused by strains resistant to vancomycin, alternative treatments include daptomycin, ceftaroline, and combination therapies, highlighting the need for more clinical trials to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteremia due to Methicillin-Resistant Staphylococcus aureus: An Update on New Therapeutic Approaches. Holubar, M., Meng, L., Alegria, W., et al.[2023]

Daptomycin is an effective alternative to vancomycin for treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and right-sided endocarditis, as shown in a randomized trial.

Despite its effectiveness, there are concerns about treatment failures due to daptomycin non-susceptibility, particularly in strains that also show reduced susceptibility to vancomycin, highlighting the need for further research on optimizing its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: the potential role of daptomycin. Bamberger, DM.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Postmarketing clinical experience in patients with skin and skin-structure infections treated with daptomycin. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Daptomycin versus Vancomycin for Bacteremia Caused by Methicillin-Resistant Staphylococcus aureus with Vancomycin Minimum Inhibitory Concentration > 1 µg/mL: A Systematic Review and Meta-Analysis [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

[Daptomycin therapy in patients with bacteremia]. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Duration of prior vancomycin therapy and subsequent daptomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteremia. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Vancomycin and daptomycin pharmacodynamics differ against a site-directed Staphylococcus epidermidis mutant displaying the small-colony-variant phenotype. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events, healthcare interventions and healthcare utilization during home infusion therapy with daptomycin and vancomycin: a propensity score-matched cohort study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Bacteremia due to Methicillin-Resistant Staphylococcus aureus: An Update on New Therapeutic Approaches. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: the potential role of daptomycin. [2021]