From JAMA, “Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial”
Importance An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis.
Objective To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT).
Design, Setting, and Participants The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period.
Interventions Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy.
Main Outcomes and Measures The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period.
Here’s the gist: This was a multicenter randomized controlled trial done in Finland that enrolled 530 patients between 18 and 60 years who were confirmed to have appendicitis by a CT scan. They were randomized to get one of two treatments, either the usual appendectomy, or antibiotic treatment with a 1-year follow-up period. The antibiotic regimen was three days of IV treatment followed by 7 days of oral therapy.
This was a noninferiority trial. Why?
Because appendectomy is the commonly accepted treatment for appendicitis, the investigators needed to show that an alternative treatment not involving surgery would not be worse than the currently accepted treatments by some margin.
The margin chosen by the researchers was 24%. Why? I’m not sure. It appears to be somewhat arbitrary. But here’s what they found. The success rate in the surgery group was 99.6%, which is not very surprising. In the antibiotic group, 73% did not need surgery within one year. That’s just stunning. They got better with antibiotics alone. That left 27% getting surgery even with antibiotics. Of those people, 83% had uncomplicated appendicitis, 10% had complicated appendicitis, and 7% didn’t have appendicitis, but had the procedure because they were being cautious.
Still, this means that 27% needed to have surgery within the one-year period. Since they defined the noninferiority margin to be 24%, this was outside of it, and, therefore, antibiotic therapy didn’t meet the predetermined criterion for being just as good as surgery.
Let’s give credit to the ethics of the researchers, who stuck by their a priori definitions and still kept the line at 24%. They could easily have left this out, and sold this as a big win. They didn’t.
But I can. For a long time, we’ve believed that everyone who has appendicitis needs to have surgery. We believed this, because making the diagnosis was hard, and it was especially difficult to distinguish between uncomplicated and complicated appendicitis. Those days are over. We can use CT and other tests to determine if a patient has uncomplicated appendicitis, and then most of those cases can be managed with antibiotics quite safely.
This is progress. Care has improved so that we can be less invasive and less costly. We should take advantage of the situation. It’s time for us to reconsider how we treat appendicitis.