NIH Grants Pitt’s Medical School $8.4 M To Determine Best Treatments for Sepsis

Sepsis is among the top causes of death in the United States, affecting 750,000 Americans each year, 30 percent of whom die. It also is one of the most expensive diseases, with a cost to U.S. hospitals of $17 billion each year. To investigate and determine the best methods for treating sepsis, the National Institute of General Medical Sciences (NIGMS), one of the National Institutes of Health, has awarded an $8.4 million, five-year grant to Pitt’s School of Medicine to head a multidisciplinary, multicenter consortium.

The Protocolized Care for Early Septic Shock (ProCESS) study will attempt to determine if there is a “golden hour” in the management of sepsis and septic shock when a prompt, rigorous, standardized treatment regimen can be used to improve clinical outcomes and halt the progression of events that often lead to organ failure and death. The study takes a cue from coronary care, which has significantly reduced mortality from acute coronary diseases and dramatically lowered the costs of care by determining such best practices.

The investigators, led by Derek C. Angus, professor and vice chair of research in the Pitt medical school’s Department of Critical Care Medicine, share a sense of urgency about their research. They hope that the project will generate useful and comprehensive data on the clinical and biological aspects of standardized treatment for septic shock—data that can have an immediate impact on, and improve care of, the critically ill.

“While we have quite an extensive understanding of the causes and course of sepsis, we have very little empirical data telling us how and when to treat this terrible disease,” Angus said. “Sepsis has reached epidemic proportions in the United States, taking as many lives as heart attacks do. It is essential that we conduct this kind of study to identify the ideal way to stop the rampant inflammation before it reaches the point where it becomes so severe and aggressive that it cannot be stopped.”

“This project will examine whether specific treatments, if given early enough, can stop sepsis in its tracks,” said NIGMS Director Jeremy M. Berg. “The goal is to speed recovery, increase survival rates, and improve the long-term quality of life for those who have had sepsis.”

Sepsis occurs when the body’s inflammatory response overreacts to an infection, resulting in a cascade of events throughout the body. The cascade begins with septic shock, then vital organs become compromised, and the syndrome progresses to multiple organ failure and death.

The trial, to be conducted at several leading hospitals around the country, will enroll up to 2,000 participants who come to emergency departments with septic shock. Participants will be randomized to receive alternative treatment protocols involving intravenous fluids, drugs that reverse the shock, and hemodynamic monitoring during the first six hours of care. The protocols will be evaluated on three measures: clinical effectiveness as evidenced by improved mortality rates; effectiveness in reducing concentrations of biological markers that are associated with the four fundamental pathways of sepsis-related organ dysfunction—cellular hypoxia, oxidative stress, inflammation and coagulation/thrombosis; and cost effectiveness.

Collaborations with emergency medicine experts is critical. The researchers note that getting septic patients the correct care the moment they enter the hospital is essential to the success of the treatment.

“ProCESS will expand our understanding of emergency department sepsis care and could revolutionize that care,” said Donald M. Yealy, professor and vice chair in the Pitt medical school’s Department of Emergency Medicine and coprincipal investigator of the study. “We will be able to better understand what type of care works and why, and improve the link between emergency and ICU care. We hope to save lives, starting at the ‘front’ door.”

“This collaborative model is one that the University of Pittsburgh has championed for years. Carrying out this clinical research is key to the mission of the department of critical care medicine, the first such department of its kind in the country,” added Mitchell P. Fink, professor and chair of critical care medicine and Watson Professor of Surgery in the Pitt medical school. “Bringing this model to sites across the country could profoundly impact critical care at the national level.”

“By improving the treatment of those critically ill with sepsis, the consortium’s work will have enormous implications for the thousands of patients who suffer from this infection,” said NIH Director Elias A. Zerhouni.