American College Of Surgeons - Inspiring Quality: Highest Standards, Better Outcomes

CODA trial weighs antibiotics against appendectomy

OCTOBER 25, 2017
Clinical Congress Daily Highlights, Wednesday Second Edition

A new clinical trial will determine whether antibiotics should replace appendectomy as the standard treatment in most cases of appendicitis, as recent evidence from Europe suggests. Such a determination would overthrow 120 years of practice using appendectomy as the standard treatment.

The Comparison of Outcomes of Drugs and Appendectomy (CODA) is a large-scale, pragmatic, randomized controlled trial comparing appendectomy to antibiotics-first for the treatment of uncomplicated appendicitis. The trial hopes to definitively answer two questions: “Are antibiotics as effective as surgery for appendicitis?” and “Which patients are most likely to have a successful outcome with antibiotics first?”

A handful of large clinical trials coming out of Europe have concluded that using antibiotics alone to treat appendicitis can result in acceptable outcomes for most people. This research has changed how appendicitis is treated by many European physicians.

But U.S. surgeons remain wary, pointing to problems with these studies. For instance, critics say the European researchers do not account for whether the benefits of avoiding an operation outweigh the potential burden of future appendicitis episodes, the number of days with antibiotics and symptoms, and anxiety about future episodes of appendicitis that may affect quality of life. As of 2014, less than 1.5 percent of all people with appendicitis in the U.S. were treated only with antibiotics.

On Tuesday, David R. Flum, MD, MPH, FACS, University of Washington, Seattle, the principal investigator of the trial, and colleagues discussed some of its features and addressed issues that have been raised about it.

The trial takes a 'total outpatient' approach, enrolling a broad cross-section of patients. This has challenged investigators not to introduce their biases as to which treatment a particular patient should receive, said Giana H. Davidson, MD, MPH, FACS, University of Washington, Seattle, who is also an investigator on the trial.

For instance, CODA includes patients with radiographic evidence of perforation and appendicolith – an approach that may run counter to the instincts of some surgeons, but it has “not been a big issue,” she said. The trial also considers a broad range of surgical approaches including laparoscopic, open and same-day surgery.

Some surgeons and patients argue that forgoing a surgical approach might miss finding cancer in the appendix, which may occur in about one in 200 appendicitis patients, Dr. Flum said. Patients treated with antibiotics in the study will be closely followed for possible missed cancer, Dr. Davidson said. The possibility of finding cancer through appendectomy is also disclosed to patients before they enter the randomized portion of the trial, she said.

A variety of substudies and ancillary studies are being planned for CODA. These include looking at the role played by biomarkers and the microbiome in appendicitis. The trial will also grade the accuracy of imaging in diagnosing appendicitis.

Ultimately, the CODA trial will give surgeons a better basis to make recommendations for how to treat uncomplicated appendicitis, Dr. Flum said.

“Please – hold off on treating your patients only with antibiotics until our trial is over,” he said. “All we are asking is that you have an open mind.”

Additional Information:
The Special Session, Challenging 120 Years of Surgical Convention: The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial, was held October 25, at the 2017 Clinical Congress of the American College of Surgeons in San Diego, CA. Program, webcast and audio information is available online at FACS.org/clincon2017.

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