The consumer advocacy group Public Citizen in a letter sent Tuesday called on federal health officials to stop enrolling patients in a clinical trial on sepsis treatment—claiming the study will put patients at risk.
Each year, about 1.5 million people in the United States develop sepsis—a medical complication resulting from the body's inflammatory response to an infection. Sepsis can cause organ systems to shut down and, in some cases, mental confusion. More than 250,000 people die from sepsis annually in the United States. Signs of sepsis include extreme pain or general discomfort, sleepiness, shortness of breath, and a shiver or a fever.
Physicians typically treat sepsis by using a combination of blood-pressure medications, called vasopressors, and IV fluids. The Society for Critical Care Medicine recommends patients with sepsis receive IV fluids within three hours and that physicians monitor patients' blood pressure to see if they need additional IV fluids to increase blood pressure levels.
However, there is no agreement on the best approach for treating sepsis, according to "Shots." Some providers rely more heavily on IV fluids than vasopressors, while others rely more on vasopressors than IV fluids, "Shots" reports.
Craig Coopersmith, an expert on sepsis and director of the surgical transplant intensive care unit at Emory University Hospital who is not involved in the latest clinical trial, said, "[T]rying to find the sweet spot—or the 'Goldilocks place'" for treating sepsis "is important." Sepsis can be fatal, and prompt treatment can be the difference between life and death.
Researchers look to determine best approach for treating sepsis
A group of researchers is looking to find that "sweet spot," "Shots" reports. To determine the appropriate mix of IV fluids and vasopressors for managing sepsis, researchers designed a clinical trial called Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis, or CLOVERS, that is funded by NIH.
Patients enrolled in the trial will first receive the quantity of IV fluids recommended by the Society for Critical Care Medicine. Then, the patients will be divided into two groups:
- One in which patients will immediately receive large volumes—about five quarts—of IV fluids and then receive a smaller quantity of vasopressors to treat their sepsis; and
- Another in which patients will immediately receive large quantities of vasopressors and then a smaller quantity of IV fluids.
The clinical trial does not have a control group.
An institutional review board at Vanderbilt University, which evaluates whether human studies are ethical and scientifically rigorous, approved CLOVERS. In March, researchers began to recruit patients for the study. Researchers hope to enroll as many as 2,320 patients at 44 U.S. hospitals and other medical sites.
Groups say trial will put patients at risk
But Michael Carome and Sidney Wolfe of Public Citizen's Health Research Group in a letter sent Tuesday urged Jerry Menikoff, director of HHS' Office for Human Research Protections (OHRP), to direct NIH's National Heart, Lung, and Blood Institute to stop enrolling patients in CLOVERS because of patient safety concerns.
Carome and Wolfe wrote that the clinical trial would place patients with sepsis at risk. They argued that instead of receiving the standard of care for managing sepsis, the patients would be treated using "experimental management strategies." Carome and Wolfe wrote that the trial could result in patients having extremely low blood pressure for several hours, which could then lead to septic shock or organ failure. They argued that patients enrolled in the trial would be "unwitting guinea pigs in a physiology experiment that will not advance medical care for sepsis."
Carome and Wolfe in the letter also claimed there are other "serious regulatory and ethical lapses related to" the trial's design. For example, they wrote that the study could generate misleading results because it does not include a control group. Carome separately explained that not having a control group would mean researchers would not be able to conclude whether a particular treatment approach is better than the standard of care.
Researchers defend the study
Researchers participating in the clinical trial disagreed with the concerns raised by Public Citizen.
Nathan Shapiro of Beth Israel Deaconess Medical Center, a co-leader of CLOVERS, said, "Our study will provide clinicians with authoritative data on which approach leads to better patient outcomes." He added, "The study protocol was designed by expert clinicians in emergency and critical care medicine," and "follows a well-accepted design" reviewed by a data safety and monitoring board.
Wesley Self, an investigator in the study and vice chair of research in the department of emergency medicine at Vanderbilt University Medical Center, said, "Nothing in the trial is experimental care." Self said the clinical trial relies on "fairly routin[e]" approaches for managing sepsis and research suggests both methods can be effective (Harris, "Shots," NPR, 8/28; Begley, STAT News, 8/28).
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