Bassett Research Institute Awarded Funding for National, Multi-Center Clinical Trial

Study Examines How Antibiotics Used to Treat Severe Infections Affect Kidneys

Bassett Research Institute has been awarded research funding of approximately $12 million from the Patient-Centered Outcomes Research Institute (PCORI) to launch a study about the effects on the kidneys of a common antibiotic regimen used to treat hospitalized patients with severe infections. Conducted in real-world care settings, the study will generate evidence on outcomes that matter most to patients, helping them and their clinicians make better-informed decisions.

Led by Daniel Freilich, MD, Medical Director of the Center for Clinical Research at the Bassett Research Institute, the project aims to resolve a decision-making challenge clinicians routinely face when deciding what antibiotics to prescribe. The research is co-led by Daniel Hanley, MD, Director of the Brain Injury Outcomes (BIOS) Clinical Trials Coordinating Center at Johns Hopkins University in Baltimore, MD. Other key sites on study leadership committees include Oregon Health and Science University in Portland, OR, Wake Forest School of Medicine in Winston-Salem, NC, West Virginia University in Morgantown, WV, and the University of Pittsburgh.

The antibiotic regimen the study will analyze is the combination of vancomycin and piperacillin/tazobactam (VPT). VPT has long been considered a standard treatment approach for hospitalized patients diagnosed with severe infections. Studies have been conducted in the past to assess the effects of these medications on the kidneys. Most have shown more acute kidney injury with VPT than with other combinations of antibiotics, like vancomycin and cefepime or vancomycin and meropenem. As a result, some experts have recommended use of these alternate non-VPT regimens to avoid kidney injury (though the alternate regimens have their own potential side effects, including brain toxicity, multidrug resistant colonization and infections, and C diff infection). Other trials have suggested VPT may not cause significant acute kidney injury at all, leading to the current challenges clinicians face when making the best recommendations to their patients when choosing an effective treatment for infection.

Bassett Research Institute’s study will seek to confirm its hypothesis that kidney function is not different among hospitalized patients with serious infections treated by VPT compared to non-VPT antibiotic therapy. Testing serum cystatin C as the study’s primary outcome, a more accurate, state-of-the-art kidney function test than the standard one, creatinine, and uniquely testing kidney urine injury markers, the study will provide a thorough understanding of kidney effects in patients treated with VPT versus the non-VPT antibiotic therapy.

“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. 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” said Freilich. “We thank PCORI for their investment in our work and we look forward to conducting this study and sharing our findings.”

Approximately 1,000 hospitalized adult patients with serious infections, for whom VPT or non-VPT would be standard treatment options, will be asked if they would like to learn about the study and potentially voluntarily participate in the study. Only patients who provide informed consent will participate. The study is safe for participants, as both antibiotic therapy approaches offer standard, evidence-based treatment approaches to infection.

Bassett Research Institute collaborated with other hospitals across the U.S. to select over two dozen enrollment sites in both urban and rural settings to address any potential under-representations. The team also engaged with patients and caregivers, patient representatives, patient advocacy organizations, and multi-disciplinary stakeholders, including specialists, pharmacists, and kidney injury biomarkers experts, for input on the study’s design. These stakeholders continue to co-manage the study on leadership committees.

“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,” said Nakela L. Cook, MD, MPH, Executive Director of PCORI. “By addressing a key evidence gap in the care of hospitalized patients with severe infections, this study has the potential to improve patient outcomes and relevance of care. We look forward to following its progress.”

Bassett Research Institute’s study was selected through PCORI’s highly competitive review process in which patients, caregivers, and other stakeholders join scientists to evaluate proposals. The funding award to Bassett Research Institute has been approved pending completion of a business and programmatic review by PCORI and issuance of a formal award contract.

PCORI is a nonprofit organization with a mission to fund research designed to provide patients, their caregivers, and clinicians with the evidence-based information needed to make better-informed health care decisions.