Bassett Research Institute Receives $12 Million PCORI Grant to Study Kidney Effects of Common Antibiotic Combination
Key Insights
Bassett Research Institute (search) has been awarded approximately $12 million from PCORI to conduct a multi-center clinical trial examining kidney (search) effects of vancomycin and piperacillin/tazobactam (search) combination therapy in hospitalized patients with severe infections (search).
The study aims to resolve clinical uncertainty about whether VPT causes more acute kidney injury (search) compared to alternative antibiotic regimens, using advanced kidney (search) function testing with serum cystatin C (search) as the primary outcome.
Approximately 1,000 hospitalized adult patients will be enrolled across over two dozen sites nationwide, with the research designed to provide evidence-based guidance for antibiotic selection in severe infections (search).
Bassett Research Institute (search) has secured approximately $12 million in funding from the Patient-Centered Outcomes Research Institute (search) (PCORI) to launch a comprehensive multi-center clinical trial examining the kidney (search) effects of a widely used antibiotic combination in hospitalized patients with severe infections (search). The study will investigate whether the vancomycin and piperacillin/tazobactam (search) (VPT) regimen causes more kidney damage than alternative antibiotic combinations.
Addressing Clinical Uncertainty
The research, led by Dr. Daniel Freilich, Medical Director of the Center for Clinical Research at the Bassett Research Institute (search), aims to resolve a persistent clinical dilemma that physicians face when selecting antibiotics for severely infected patients. The study is co-led by Dr. Daniel Hanley, Director of the Brain Injury Outcomes Clinical Trials Coordinating Center at Johns Hopkins University, with additional leadership from Oregon Health and Science University, Wake Forest School of Medicine, West Virginia University, and the University of Pittsburgh.
VPT has long been considered a standard treatment approach for hospitalized patients with severe infections (search). However, previous studies have produced conflicting results regarding its impact on kidney (search) function. Most studies have shown more acute kidney injury (search) with VPT compared to other antibiotic combinations like vancomycin and cefepime or vancomycin and meropenem. This has led some experts to recommend alternative non-VPT regimens to avoid kidney injury, though these alternatives carry their own potential side effects, including brain toxicity (search), multidrug resistant colonization and infections, and C. diff infection.
Conversely, other trials have suggested VPT may not cause significant acute kidney injury (search) at all, creating the current uncertainty that clinicians face when making treatment recommendations.
Advanced Methodology and Study Design
The Bassett Research Institute (search) study will test the hypothesis that kidney (search) function is not different among hospitalized patients with serious infections treated with VPT compared to non-VPT antibiotic therapy. The research will employ serum cystatin C (search) as the primary outcome measure, which represents a more accurate, state-of-the-art kidney function test compared to the standard creatinine test. Additionally, the study will uniquely test kidney urine injury markers to provide a comprehensive understanding of kidney effects.
Approximately 1,000 hospitalized adult patients with serious infections will be enrolled in the study, with participation limited to those for whom either VPT or non-VPT would be standard treatment options. Only patients who provide informed consent will participate, and the study is considered safe as both antibiotic therapy approaches represent standard, evidence-based treatment options.
Multi-Site Collaboration and Stakeholder Engagement
The research institute has collaborated with hospitals across the United States to establish over two dozen enrollment sites in both urban and rural settings to address potential under-representation issues. The study design has incorporated input from patients and caregivers, patient representatives, patient advocacy organizations, and multi-disciplinary stakeholders, including specialists, pharmacists, and kidney (search) injury biomarkers experts. These stakeholders continue to co-manage the study through leadership committees.
"The results of this study aim to help hospitalized patients by improving the quality of their care, their safety, and potentially decreasing complications they may encounter," said Dr. Freilich. "It aims to help specialty organizations that write clinical practice guidelines by giving them information to update protocols and stop variance in practice due to the current gap in information. It also helps healthcare systems and insurers implement standards for best practices for antibiotics therapy in hospitalized patients."
Clinical Impact and Future Implications
Dr. Nakela L. Cook, Executive Director of PCORI, emphasized the study's potential impact: "Patient-centered comparative clinical effectiveness research puts the spotlight on outcomes that matter most to people and provides families and individuals with evidence to make informed healthcare decisions. By addressing a key evidence gap in the care of hospitalized patients with severe infections (search), this study has the potential to improve patient outcomes and relevance of care."
The study was selected through PCORI's competitive review process, which uniquely includes patients, caregivers, and other stakeholders alongside scientists in evaluating research proposals. The funding award has been approved pending completion of business and programmatic review by PCORI and issuance of a formal award contract.