Vancomycin Dosing for MRSA Infections

(VIVID Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Anthony D Bai, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Hamilton Health Sciences Corporation

Disqualifiers: Vancomycin MIC ≥2ug/mL, Palliative, Dialysis, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests two ways of giving vancomycin to patients with serious MRSA infections. It aims to find out if a simpler dosing method is as effective as a more complex one. Vancomycin is the antibiotic with the most clinical experience for treating MRSA bacteremia.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you can participate if you are not currently on vancomycin or have been on it for 4 days or less.

What data supports the effectiveness of the drug Vancomycin for MRSA infections?

Research shows that Vancomycin is effective for treating MRSA infections, especially when the drug concentration in the body is carefully monitored and adjusted. Studies suggest that achieving a specific drug concentration (AUC/MIC ratio of ≥400) is linked to better treatment outcomes, reducing the chance of treatment failure. ^{1 2 3 4 5}

Is vancomycin generally safe for humans?

Vancomycin has been used for a long time to treat serious infections, but there are risks of drug toxicity (harmful effects) if not prescribed correctly. Recommendations exist to monitor its use carefully to minimize these risks. ^{2 6 7 8 9}

How is the drug Vancomycin unique in treating MRSA infections?

Vancomycin is unique in treating MRSA infections because it requires careful dosing to achieve specific drug concentration levels in the body, measured by the area under the concentration versus time curve (AUC) divided by the minimum inhibitory concentration (MIC) of the bacteria. This approach helps ensure the drug is effective, especially in critically ill patients, and differs from traditional dosing methods that focus only on trough concentrations. ^{1 3 8 10 11}

Research Team

Anthony D Bai, MD

Principal Investigator

Hamilton Health Sciences Corporation

Eligibility Criteria

Adults with serious MRSA infections confirmed by culture, including blood, lung, brain, bone infections and more. They must join within 4 days of the culture test and can be new to vancomycin treatment or have had it for up to 4 days. Not eligible if they're on dialysis, expected to die within 48 hours, allergic to vancomycin or if their infection resists higher doses of vancomycin.

Inclusion Criteria

I am not currently on vancomycin or have been on it for 4 days or less.

I have a serious MRSA infection confirmed by lab tests.

Enrolment within 4 days from date of MRSA culture collection

Exclusion Criteria

History of type 1 hypersensitivity reaction to vancomycin

Vancomycin minimum inhibitory concentration (MIC) ≥2ug/mL

You are receiving end-of-life care and are expected to pass away within the next two days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous vancomycin with dosing strategy targeting either a trough level of 10 to 15mg/L or an AUC of 400 to 600 for serious MRSA infections

90 days

Regular monitoring visits for dose adjustments

Follow-up

Participants are monitored for treatment failure, defined as death or microbiologic failure, and other secondary outcomes such as nephrotoxicity and renal replacement therapy

90 days

Treatment Details

Interventions

• Vancomycin (Glycopeptide Antibiotic)

Trial Overview This study tests two ways of dosing vancomycin in treating serious MRSA infections: one targets drug levels in the blood (trough level) and the other focuses on how much drug stays in the body over time relative to the bacteria's resistance (AUC/MIC). It checks which method is just as good without being worse by more than a set margin.

Participant Groups

Group I: Vancomycin targeting trough of 10 to 15mg/L Experimental Treatment 1 Intervention

If the patient has not received intravenous vancomycin yet, a loading dose of 25mg/kg (maximum 2g) will be given if the patient is severely ill at the discretion of the physician and pharmacist. The initial dose is 15mg/kg with a maximum dose of 2g. The frequency would be based on creatinine clearance (CrCl) as per the Cockcroft-Gault equation: Q8H if CrCl is \>100mL/min, Q12H if CrCl is 50-100mL/min, Q24H if CrCl is 30- 49mL/min, and Q48H if CrCl is \<30mL/min. Pharmacists can change the initial dose at their own discretion. Trough level will be done 30 minutes before the 4th dose. For Q48H dosing, a trough level will be done before the second dose. Vancomycin dosing will be adjusted to target trough level of 10 to 15mg/L. If not at target, the pharmacist will adjust the dose based on an assumption of linear pharmacokinetics. Trough will be remeasured before the fourth dose of the new regimen.

Group II: Vancomycin targeting AUC of 400 to 600 Active Control 1 Intervention

The initial intravenous vancomycin dosing is the same as described above for the trough group. The AUC target will be 400 to 600, which assumes a MIC of 1ug/mL by broth microdilution. After the first non-loading dose of vancomycin, patients will have vancomycin level 30 minutes before the next dose. As per the pharmacist's discretion, patient may have an additional vancomycin level one hour after infusion of vancomycin for more accurate estimates. A pharmacist will use a Bayesian software to estimate the AUC and the optimal dose.

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

🇺🇸 Approved in United States as Vancocin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus
• Staphylococcal endocarditis

🇪🇺 Approved in European Union as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)

🇨🇦 Approved in Canada as Vancomycin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus

🇯🇵 Approved in Japan as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

McGill University Health Centre Montreal, Canada

Hamilton Health Sciences Hamilton, Canada

Kingston Health Sciences Centre Kingston, Canada

St. Joseph's Healthcare Hamilton Hamilton, Canada

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Patients Recruited

345,000+

McMaster University

Lead Sponsor

Trials

936

Patients Recruited

2,630,000+

Physician Services Incorporated

Collaborator

Trials

2

Patients Recruited

850+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1417

Patients Recruited

26,550,000+

The Physicians' Services Incorporated Foundation

Collaborator

Trials

165

Patients Recruited

31,700+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid. Hamilton, LA., Christopher Wood, G., Magnotti, LJ., et al.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia. Yoon, JG., Huh, K., Sohn, YM., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin pharmacokinetic models: informing the clinical management of drug-resistant bacterial infections. Stockmann, C., Roberts, JK., Yu, T., et al.[2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Appropriateness of an Initial Dosing Regimen of Vancomycin and Development of a New Dosing Nomogram. Yoon, S., Park, KR., Lee, S., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Silico Pharmacokinetic Study of Vancomycin Using PBPK Modeling and Therapeutic Drug Monitoring. Ferreira, A., Martins, H., Oliveira, JC., et al.[2021]

Vancomycin is regaining attention due to its effectiveness against resistant gram-positive bacteria and improvements in its drug purity, making it a valuable option in treating infections.

The review highlights vancomycin's antimicrobial activity, pharmacokinetics, clinical uses, dosing regimens, and potential side effects, providing a comprehensive overview for healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin. A new old agent. Ingerman, MJ., Santoro, J.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes. Phillips, CJ., Gordon, DL.[2022]

In a study of 23 pediatric patients with MRSA infections, 52% experienced treatment failure, particularly in those with minimum inhibitory concentrations (MICs) of 1.5 µg/mL or higher, indicating a significant challenge in effectively treating these infections.

Only 18% of patients achieved the recommended vancomycin trough levels of >15 µg/mL, and none reached the optimal AUC24/MIC ratio of >400, suggesting that current dosing guidelines may be inadequate for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of clinical outcome in children and adolescents receiving vancomycin for invasive infections due to methicillin-resistant Staphylococcus aureus: impact of increasing vancomycin MICs. Arun, A., Swamy, S., Jacob, K., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of ASHP/IDSA/SIDP vancomycin monitoring recommendations: a focus on osteomyelitis. Malloy, KM., Davis, GA.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin dosing for pneumonia in critically ill trauma patients. Patanwala, AE., Norris, CJ., Nix, DE., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates. Lim, CP., Tseng, SH., Neoh, CCC., et al.[2022]

References

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

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid. [2015]

2. China pubmed.ncbi.nlm.nih.gov

Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Vancomycin pharmacokinetic models: informing the clinical management of drug-resistant bacterial infections. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Assessment of Appropriateness of an Initial Dosing Regimen of Vancomycin and Development of a New Dosing Nomogram. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

In Silico Pharmacokinetic Study of Vancomycin Using PBPK Modeling and Therapeutic Drug Monitoring. [2021]

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

Vancomycin. A new old agent. [2013]

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

Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Evaluation of clinical outcome in children and adolescents receiving vancomycin for invasive infections due to methicillin-resistant Staphylococcus aureus: impact of increasing vancomycin MICs. [2018]

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

Summary of ASHP/IDSA/SIDP vancomycin monitoring recommendations: a focus on osteomyelitis. [2013]

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

Vancomycin dosing for pneumonia in critically ill trauma patients. [2022]

11. France pubmed.ncbi.nlm.nih.gov

External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates. [2022]