APPY trial compares appendicitis treatment failure rates
High-impact journal The Lancet just published a first-of-its-kind study led by Shawn St. Peter, MD, Senior Vice President, Surgeon-in-Chief and Interim Chief Scientific Officer, Children's Mercy Kansas City.
“Appendicectomy* versus antibiotics for acute uncomplicated appendicitis in children” describes the APPY Trial, the first large-scale, randomized clinical trial on the subject. Dr. St. Peter’s co-authors from Children’s Mercy included Janelle R. Noel-MacDonnell, PhD, Health Services and Outcomes, and Pete Muenks, ACRP-CP, Senior Clinical Research Coordinator, Children’s Mercy Research Institute (CMRI).
The APPY trial ran between January 2016 and December 2021. It included 11 children’s hospitals and 936 patients, 5 to 16 years old, with suspected non-perforated appendicitis. Families who chose to participate in the trial were randomly assigned a treatment path: antibiotics or appendectomy.
The study compares the failure rates of those two unequal options: Antibiotics avoid surgery but can come with unpleasant side effects and a chance of recurrence. Appendectomies are low-risk surgeries with short recovery times and no risk of recurrence.
“The question is what recurrence rate would you accept in order to avoid an operation?” said Dr. St. Peter. “As a working group, we settled on greater than a 20% difference in failure rates would be inferior.”
With a failure rate difference outside of that acceptable range, the study concluded that “antibiotic treatment for uncomplicated appendicitis in children was inferior to appendectomy in this trial.”
The study also found that the total time spent in the hospital was shorter with appendectomies. That outcome was influenced by the antibiotic treatment’s in-hospital IV protocol and recurrences that sent patients back to the hospital. However, patients treated by antibiotics bounced back to “normal function” a little faster than appendectomy patients, who needed to recover from surgery.
A real-world study
For patients treated with surgery, the study considered a negative appendectomy (when the removed appendix shows no signs of disease) a failure (7%). For patients treated with antibiotics, failure was defined as needing to have an appendectomy within one year (34%). Most of those appendectomies happened within the first 100 days.
“What does Mom think of that number?” said Dr. St. Peter of that 1/3 chance of appendicitis recurrence after antibiotic treatment. “It’s within the eye of the beholder. If somebody’s terrified of an operation, that might seem reasonable.”
The antibiotics failure rate included patients who were assigned antibiotic treatment but whose families later requested an appendectomy. “This is a pragmatic, real-world study,” said Dr. St. Peter. “You’re going to have dissatisfied families that within a day or two are going to say, ‘enough.’”
Research informs future treatment guidelines
The study fills a needed gap in appendicitis treatment literature and provides evidence-based talking points for discussing treatment options with parents.
"We know what the failure rates are for all stratifications of patients with appendicitis,” said Dr. St. Peter. “Now that we’ve got the playing rules, we can put together the game.”
The team will continue to research the most beneficial place for antibiotics in appendicitis treatment pathways. They are currently submitting a grant to study sending patients home from the ER with oral antibiotics (instead of the current study’s protocol of starting with 12+ hours of IV antibiotics). “If that were to be successful, then, the next evolution could be point-of-care antibiotic treatment for early appendicitis.”
* “Appendicectomy” is the British spelling of “appendectomy” used by The Lancet.