Daptomycin vs. Vancomycin for Staph Bacteremia

(DAPTO-SNAP Trial)

Recruiting at 12 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness of vancomycin (Vancocin) and daptomycin (Cubicin) for treating bloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA). It aims to determine which drug more effectively treats these challenging bacterial infections. Participants must have a current MRSA infection in their blood and no serious allergies to the study drugs. The research aims to improve care for those with MRSA bloodstream infections. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, and this research seeks to understand how they can benefit more patients.

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 is the safety track record for daptomycin and vancomycin?

Research has shown that daptomycin is generally well-tolerated by patients with bloodstream infections caused by S. aureus, including methicillin-resistant strains (MRSA). Studies indicate it is effective and safe even for individuals with mild to moderate kidney issues. In one study, daptomycin successfully treated 79% of bloodstream infections not related to catheters.

Daptomycin is not less effective than standard treatments for these infections and has been proven safe in various clinical trials. It is already approved for treating complicated skin infections and certain bloodstream infections, supporting its safety.

Vancomycin, the other treatment in this trial, is a well-known antibiotic often used for MRSA infections. It is generally considered safe when properly monitored, especially to manage doses and prevent kidney-related side effects. Both daptomycin and vancomycin have been widely used, indicating their safety for treating MRSA infections. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Daptomycin for treating Staph bacteremia because it offers a distinct mechanism of action compared to traditional options like Vancomycin. Most treatments for this condition work by inhibiting cell wall synthesis, but Daptomycin disrupts the bacterial cell membrane, leading to rapid bacterial death. This unique approach can be especially beneficial for patients with resistant strains, offering a potential advantage over the standard treatments. Additionally, Daptomycin is administered at a flexible dosage determined by clinicians, which can be tailored to individual patient needs.

What evidence suggests that this trial's treatments could be effective for MRSA bloodstream infection?

This trial will compare Daptomycin and Vancomycin for treating MRSA bloodstream infections. Studies have shown that Daptomycin, which participants in this trial may receive, succeeds in about 89% of cases for treating these infections. Research also indicates that Daptomycin is as effective as standard treatments like Vancomycin, another option in this trial. Vancomycin has been a common treatment for MRSA infections for many years. A study comparing the two found that Daptomycin might slightly reduce the risk of death compared to Vancomycin, but the difference was not significant. Both treatments reliably manage MRSA bloodstream infections. ^{1 2 3 4 6}

Who Is on the Research Team?

Todd C Lee, MD MPH FIDSA

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3591880/

Multicenter Evaluation of the Clinical Outcomes of Daptomycin ... In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1198743X14606595

Clinical outcomes with daptomycin: a post-marketing, real- ... Overall treatment success with daptomycin for bacteraemia was 89%, and was similar for catheter-related and non-catheter-related infections (Table 2). No ...

3. academic.oup.com academic.oup.com/ofid/article/12/2/ofaf012/7959270

Evaluation of Daptomycin Use in Outpatients With Methicillin ... We compared standard dose daptomycin (<8 mg/kg) vs high dose (≥8 mg/kg) for methicillin-sensitive S aureus bloodstream infections.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa053783

Daptomycin versus Standard Therapy for Bacteremia and ... Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis.

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0293423

Comparative effectiveness of daptomycin versus vancomycin ... Daptomycin treatment was associated with non-significant lower mortality odds, compared to vancomycin treatment (OR = 0.81; 95% CI, 0.62, 1.06).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01728376

NCT01728376 | Safety & Efficacy of Daptomycin Versus ... Clinical trials in adults demonstrated that daptomycin was safe and efficacious in complicated skin and skin structure infections (cSSSI) and bloodstream ...