This month’s Paper of the Month comes from The CODA Collaborative.

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis
The CODA Collaborative, The New England Journal of Medicine, 5 October 2020
DOI: 10.1056/NEJMoa2014320

What is known about this subject?

The APPAC study showed that antibiotics can be used as an alternative to appendicectomy in the treatment of acute appendicitis with 61% of patients avoiding surgery at 5 years follow-up. Other studies were performed to answer the same question, however, these studies were criticised for issues like being very selective, having small sample sizes, or the uncertainty of diagnosis. The CODA study was designed as a pragmatic patient outcome focused study to compare antibiotics with appendicectomy for appendicitis.

What does this study add?

Design: Multicentre nonblinded, noninferiority, randomized trial including 25 U.S. centres. Intention to treat analysis was followed and subgroup analysis of patients with appendicolith was performed.

Primary endpoints: The primary outcome was 30-day health status using the European Quality of Life–5 Dimensions (EQ-5D) questionnaire. A noninferiority margin of 0.05 points was used.

Secondary endpoints: The Secondary outcomes included the rate of appendectomy in the antibiotics group and 90 days complications in both groups.


  • 1552 patients were randomized (out of 8168 screened)
  • 96% had appendicitis confirmed on CT (+/- USS) or MRI scan and 27% had appendicolith.
  • Antibiotics were non-inferior to appendicectomy in the mean 30-day EQ-5D score (1ry outcome)
  • Antibiotics group:
    • 47% were discharged home from ED but more were readmitted within 90 days (24% vs 5%)
    • 29% had appendicectomy within 90 days (41% in those with appendicolith)
    • Less work missed (5.3 days Abx vs 8.7 days Appendicectomy)
    • More complications (8% Abx vs 3.5% Appendicectomy)
  • Appendiceal neoplasms were identified in nine participants (mean age, 47±17 years; range, 21 to 74). Seven in the appendectomy group and two in the antibiotics group who had undergone appendicectomy.
  • The rate of use of more extensive procedures was low and similar in the two groups (1% vs. 0.8% participants).
  • The percentage with perforation was higher in the antibiotics (32% vs. 16%) and even higher in those with an appendicolith (61% vs. 24%)

Implications for colorectal practice?

Unlike previous studies, the CODA study was designed as a pragmatic trial and included patients with faecolith and only patients with radiologically confirmed appendicitis. The primary outcome aimed at the patient experience. While antibiotic treatment was found to be non-inferior to surgery, the same conclusion does not apply to patients with faecolith. The diagnosis of appendicular fecolith usually requires a CT scan which is not considered as a routine practice in the UK unlike the USA and Europe.

The risk of missing appendiceal neoplasms with the antibiotic approach is important. Subsequent investigation to exclude cancer in some patients and the financial burden from readmission and repeated investigations have not been investigated yet.

Finally, the results from CODA trial support the conservative management of acute appendicitis during the COVID pandemic and should be considered in consenting patients for appendicectomy.