Written by Physician’s Weekly blogger, Skeptical Scalpel

The short-term results of the CODA trial have just been published in the New England Journal of Medicine. This study of over 1500 patients randomized to either appendectomy or antibiotics and found that antibiotic therapy is non-inferior to appendectomy when measured by the primary outcome of 30-day health status using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. That outcome was chosen with input from patients who were asked about outcomes they considered most important.

The study involved 25 clinical sites in the United States. The diagnosis of appendicitis was confirmed by CT scan, ultrasound, or MRI in 96% of patients with 27% having an appendicolith [stone in the appendix]. Signs of perforation on imaging studies did not necessarily exclude patients. After randomization, 776 patients, well-matched for both clinical and demographic characteristics, were assigned to each group.

Laparoscopic appendectomy was performed in 96% of patients in the surgery group. Patients in the antibiotic group received intravenous antibiotics within 24 hours of randomization and were discharged home with oral antibiotics. Hospital lengths of stay averaged 1.3 days in both groups. One or more additional courses of antibiotics were prescribed in 11% of patients in the antibiotic group.

The presence of an appendicolith did not affect the non-inferiority of antibiotics. At 48 hours after entering the study, 11% of patients in the antibiotic group required an appendectomy. The need for appendectomy was 20% at 30 days and 29% at 90 days. In the antibiotic group, the presence of an appendicolith was associated with the need for appendectomy in 41% of patients as opposed to 25% for those without an appendicolith.

At 7, 14 and 30 days, resolution of symptoms such as pain, tenderness, and fever was similar in both groups. A visit to an emergency department or urgent care facility occurred in 9% of those in the antibiotic group and 4% in the appendectomy cohort; 24% of patients treated with antibiotics required hospitalization after the initial treatment compared to 5% of those who underwent appendectomy first. The appendectomy group missed an average of 3.5 more days of work.

Nine tumors were found in the combined study participants, seven in the appendectomy group and two in the antibiotic group who eventually had surgery. Eight were carcinomas and one was a mucocele. The long-term implications for the unknown number of appendiceal carcinomas in those treated with antibiotics alone are also unknown.

No patients in either group died. Complications occurred in 8.1% of antibiotic treated patients compared to 3.5% in the appendectomy group, and serious adverse events occurred in 4% and 3% of patients, respectively. The presence of an appendicolith was associated with higher rates of complications and more appendiceal perforations in both groups. At 90 days, 41% of patients with appendicoliths in the antibiotic group required an appendectomy.

Regarding the significance of appendicoliths, corresponding author Dr. David R. Flum, Professor of Surgery at the University of Washington in Seattle, said in an email, “In my counseling of patients I plan to highlight the 41% appy rate and higher complication rate and recommend surgery unless the patient has a compelling reason not to have surgery.”

The study results were originally to be published after all participants had been followed for at least one year, but because of issues related to Covid-19, the authors published sooner. The CODA study gives surgeons guidance regarding informed consent discussions for patients who present with appendicitis. Those patients who choose treatment with antibiotics can do so with the knowledge that the results are non-inferior to surgery at least in terms of short-term quality of life.

In an accompanying editorial, gastrointestinal surgeon Danny Jacobs, who is President of Oregon Health and Science University, said “I believe that most providers would recommend surgical treatment for uncomplicated appendicitis if that option is available. I know I would.”

I agree.

After a median follow-up of seven years, 39% of those treated with antibiotics required appendectomy in the Finnish randomized trial of surgery vs. antibiotics for appendicitis. At 90 days, 29% of those in the CODA antibiotic group had to undergo appendectomy. What the percentage will be in a few more years remains to be seen.


Skeptical Scalpel is a retired surgeon and was a surgical department chair and residency program director for many years. He is board-certified in general surgery and a surgical sub-specialty and has re-certified in both several times.For the last 9 years, he has been blogging at SkepticalScalpel.blogspot.com and tweeting as @SkepticScalpel. His blog has had more than 3,700,000 page views, and he has over 21,000 followers on Twitter.