Continuous vs Intermittent Vancomycin Infusion for Infections

Overseen By Aaron M Cook, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Aaron Cook

Must be taking: Vancomycin

Disqualifiers: Chronic kidney disease, Pregnancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how two methods of administering the antibiotic vancomycin affect kidney health in hospitalized adults. Vancomycin can be given continuously or in separate doses, and researchers aim to determine which method is better for the kidneys. Hospitalized individuals who have been prescribed at least two doses of vancomycin and do not have kidney issues like chronic kidney disease may be suitable for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits 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 focuses on how vancomycin is given, so it's best to ask the trial team for guidance.

What is the safety track record for vancomycin?

Research shows that about 20% of patients taking vancomycin, an antibiotic, experience harmful reactions. This occurs whether the drug is administered continuously or in separate doses. Continuous dosing might benefit some very sick patients, but both methods are generally safe. Such studies help researchers understand how different administration methods compare in terms of safety and effectiveness. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores two different ways of administering vancomycin, a well-known antibiotic used to treat serious bacterial infections. Typically, vancomycin is given in intermittent doses, but this study is comparing that approach to a continuous infusion method. The continuous infusion could potentially maintain more stable drug levels in the body, which might improve effectiveness and reduce side effects. By finding out which method works better, this trial could lead to improved treatment protocols and better outcomes for patients battling infections.

What is the effectiveness track record for vancomycin in treating infections?

This trial will compare continuous versus intermittent infusion of vancomycin for treating infections. Research has shown that vancomycin effectively treats certain bacterial infections. One study found that continuous vancomycin infusion might lower the risk of kidney damage compared to separate doses. Another review found that maintaining the right drug levels in the blood can improve recovery and protect the kidneys. While administering vancomycin in separate doses has been common and effective, some studies suggest it might be more expensive than continuous dosing. Overall, both methods work, but continuous dosing might offer better kidney safety. ^{2 3 4 5 6}

Who Is on the Research Team?

Aaron M Cook, PharmD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for hospitalized adults at the University of Kentucky who need vancomycin treatment, are over 18 years old, and can give consent. It's not for those with chronic kidney disease, recent acute kidney injury, prior vancomycin use within 72 hours (except loading dose), allergy to iohexol, uroepithelial tumors, prisoners, pregnant women or individuals with end-stage kidney disease.

Inclusion Criteria

My doctor has prescribed me two or more doses of vancomycin.

I can sign or have someone legally allowed to sign for me.

Hospitalized at University of Kentucky on a medical service (internal medicine or medical intensive care)

Exclusion Criteria

Allergy to iohexol

Pregnancy

Prisoner

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive vancomycin via continuous or intermittent infusion with kidney function and injury biomarkers collected

5 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of major adverse kidney events

Up to 17 days

What Are the Treatments Tested in This Trial?

Interventions

• Vancomycin

Trial Overview The study compares two ways of giving vancomycin: a continuous infusion versus an intermittent infusion. Participants will be randomly assigned to one method and their kidney function will be monitored to see which method is safer and more effective.

How Is the Trial Designed?

Group I: Vancomycin continuous infusion Active Control 1 Intervention

Continuous infusion of Vancomycin

Group II: Vancomycin intermittent infusion Active Control 1 Intervention

Intermittent infusion of vancomycin

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

Who Is Running the Clinical Trial?

Aaron Cook

Lead Sponsor

Trials

2

Recruited

80+

Alexander Flannery

Lead Sponsor

Trials

2

Recruited

90+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 12 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, both continuous and intermittent infusion of vancomycin effectively eradicated the infections after 10 days of treatment, demonstrating the efficacy of both methods.

No adverse events related to vancomycin were observed during the study, indicating that both infusion methods are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus. Jaruratanasirikul, S., Julamanee, J., Sudsai, T., et al.[2013]

Continuous infusion (CI) of vancomycin may reduce the risk of kidney injury compared to intermittent infusion (II), based on a meta-analysis of six studies, although some studies showed mixed results.

CI allows for more reliable monitoring of steady-state serum concentrations, which may improve dosing accuracy compared to the traditional trough level monitoring used in II, making it a potentially better option for vancomycin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion. Waineo, MF., Kuhn, TC., Brown, DL.[2015]

An updated meta-analysis of seven studies suggests that continuous infusion (CI) of vancomycin may be associated with a non-significant trend towards reduced nephrotoxicity compared to intermittent infusion, although the results were not statistically significant (risk ratio=0.799).

Despite the potential benefits of CI in reducing kidney damage, further research, particularly a large randomized controlled trial, is needed to confirm these findings and establish clear guidelines for vancomycin administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion. Hanrahan, T., Whitehouse, T., Lipman, J., et al.[2022]

A review of 9 studies, including 1 pediatric and 8 adult populations, found that while continuous infusion of vancomycin may offer pharmacodynamic advantages, the overall clinical efficacy compared to intermittent dosing remains inconsistent.

The highest quality studies showed some benefits for continuous infusion in pharmacokinetics, but mixed results in clinical outcomes suggest that continuous infusion is not routinely recommended for treating multidrug-resistant gram-positive infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Continuous and Intermittent IV Infusion of Vancomycin: Systematic Review. Man, SS., Carr, RR., Ensom, MH.[2021]

In a study of 129 critically ill patients receiving continuous vancomycin infusion, 29.5% developed acute kidney injury (AKI), indicating a significant risk associated with this treatment method.

Risk factors for AKI included higher body weight, presence of diabetes, increased need for vasopressors, and prolonged treatment duration, especially when vancomycin levels exceeded 30 μg/mL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. Spapen, HD., Janssen van Doorn, K., Diltoer, M., et al.[2021]

Continuous vancomycin infusion (CVI) significantly improves the ability to achieve therapeutic drug levels within 48 hours compared to intermittent infusion (IVI), with 54.8% of CVI patients reaching targets versus only 25.6% of IVI patients.

CVI results in fewer subtherapeutic episodes (0 vs 1) while having a higher number of supratherapeutic episodes (2 vs 1), but overall, there are no differences in treatment success, mortality, or acute kidney injury between the two methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Vancomycin Infusion versus Intermittent Infusion in Critically Ill Patients. Maluangnon, C., Tongyoo, S., Permpikul, C.[2023]

Continuous vancomycin infusion is as effective as intermittent infusion based on a systematic review of six studies, with some evidence suggesting it may be more effective for patients with osteomyelitis.

Continuous infusion is associated with a lower risk of rapid nephrotoxicity and offers advantages such as lower costs and simpler serum level monitoring, potentially allowing for quicker hospital discharges and easier home care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Continuous and intermittent infusion of vancomycin equally effective: review of the literature]. van Maarseveen, EM., Man, WH., Touw, DJ., et al.[2018]

In a study of 150 trauma ICU patients, continuous infusion of vancomycin led to a significantly faster time to reach therapeutic drug levels (2.5 days) compared to intermittent dosing (3.8 days), with a higher success rate in achieving target levels (60% vs 40%).

Continuous infusion also resulted in fewer blood samples needed (1 vs 3 per patient) and reduced nephrotoxicity (21% vs 43%), suggesting it may be a safer and more efficient method for administering vancomycin in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Continuous Infusion Vancomycin Administration in a Critically Ill Trauma Population. Bissell, BD., Riggi, G., Morrison, C.[2021]

Continuous infusion (CoI) of vancomycin significantly reduces the risk of nephrotoxicity compared to intermittent infusion (InI), with a relative risk of 0.6 based on one randomized clinical trial and five observational studies.

There was no significant difference in overall mortality between CoI and InI, indicating that while CoI may be safer regarding kidney function, its impact on survival rates needs further investigation through randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. Cataldo, MA., Tacconelli, E., Grilli, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9137986/

Clinical Efficacy and Safety of Vancomycin Continuous ... All patients who completed the e-survey were satisfied with their vOPAT course. These findings show that a structured vOPAT program with ...

2. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2833

Patient safety outcomes for continuous infusion vancomycin ... Estimates vary, but approximately 20% of patients receiving vancomycin as OPAT experience an adverse drug event (ADE) during treatment.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK97653/

Continuous versus intermittent infusion of vancomycin ... - NCBI This review concluded that (in treating Gram-positive infections) there was less risk of nephrotoxicity associated with continuous infusions of vancomycin ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0924857923002790

Review Serum concentration of continuously administered ... Mortality was reduced and clinical cure increased at concentrations >15 mg/L. Acute kidney injury was reduced at concentrations <25 mg/L.

5. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07618-6

a prospective interventional study | BMC Infectious Diseases As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37248438/

Patient safety outcomes for continuous infusion ... There was no appreciable benefit of continuous infusion vancomycin on outpatient safety outcomes. AUC-centered dosing approaches warrant further investigation.