CODA trial examining viability of antibiotic-only treatment for appendicitis

The leaders of The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial provided an inside look at the ongoing randomized clinical trial, which is still recruiting, during a panel discussion Wednesday.

Surgeons know that antibiotics can be used to treat appendicitis, noted principal investigator David R. Flum, MD, MPH, FACS, a general surgeon at the University of Washington (UW) Medicine, Seattle, but CODA will try to determine if it’s the best treatment approach. Dr. Flum led the session, Challenging 120 Years of Surgical Convention: The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial. 

“What we know about this disease is a much shorter list than what we don’t know about this disease,” Dr. Flum said. “So come into this [discussion] with the spirit of open-mindedness, because that’s the way we’re approaching the CODA trial.”

Dr. Flum noted that some European randomized trials have shown positive results for antibiotic treatment versus appendectomy, but he called the evidence base “horrible.” Meanwhile, very little is known in the U.S. about how antibiotic treatment works, he said. 

“Who does this work in best, and who doesn’t it work in best?” Dr. Flum said. “And remember that it’s not going to be a yes-or-no answer. For some people, it’s going to be the right treatment. We just need to figure out what are the things people need to hear and learn about to make the decisions for themselves.”

Giana Hystad Davidson, MD, MPH, FACS, a CODA trial leader, general surgeon, and assistant professor at UW Medicine, said that the idea for the CODA trial originated at UW Medicine, where some surgeons have become interested in antibiotic treatment. Patients ask questions about treatment options in the emergency department, she said, and have indicated they prefer an approach that will get them back to work or caring for their children faster, and a treatment that provides the cheapest out-of-pocket cost.

“These were the questions that were critical to patients, so we wanted to design a trial that was able to answer them to help us get to shared decision making,” Dr. Davidson said. “So we asked this question: Are antibiotics as effective as an appendectomy for appendicitis, and then which of the patients are most likely to have a successful outcome with antibiotic therapy?”

The trial was designed to be pragmatic, taking place in real-world settings with adults of all ages, with minimal exclusions, and with flexibility both in terms of the types of surgery and antibiotics used. The investigators are seeking heterogeneity in patients, clinicians, and health care settings.

At the 20 trial centers participating across the country, all patients with uncomplicated appendicitis have been approached, and so far 1,552 have agreed to be randomized into either the antibiotic or appendectomy arm. Clinical outcomes to be compared include rate of appendectomy in the antibiotics arm, complications and extent of operation, complications associated with antibiotics, and antibiotic days beyond initial treatment. 

The primary outcome measure for CODA is patient-reported quality of life, as measured by Euro Qol (EQ-5D) at 30 days after treatment. Secondary outcome measures include time of return to usual function, 10 PROMIS Global Health Short Form, work productivity index, Gastrointestinal Quality of Life Index (GIQLI), and decision regret. 

Early data from CODA should come in the next year or two, Dr. Flum said. But with so many questions yet to be answered, he emphasized that surgeons need to hold off on treating patients with antibiotics until the trial is completed.

“Antibiotics can work,” he said. “All of us have used [antibiotic therapy] and think we know the patients it’s right to do it in, but we really don’t know overall if it should be done. And that needs to be a clear message from the surgical community. We know it can work—we don’t know if it should be done.”