Results Summary
What was the research about?
Appendicitis occurs when the appendix, a small part of the intestine, gets infected. Without treatment, the appendix can burst, and the infection can spread.
Doctors can treat appendicitis with surgery or antibiotics. In the United States, most doctors treat with surgery to remove the appendix. Studies from Europe show that, for many patients, antibiotics are safe and work well to treat appendicitis.
In this study, the research team wanted to learn if treating patients with antibiotics was as safe and effective as surgery. Patients who received antibiotics took them for 10 days.
What were the results?
The research team assigned half the patients by chance to surgery and half to antibiotics. One month after treatment, general health was no worse for patients assigned to receive antibiotics than it was for those assigned to receive surgery.
Three months after treatment, 29 percent of patients treated with antibiotics went on to receive surgery.
Also, after three months, compared with patients who received surgery, those who received antibiotics:
- Were more likely to have had a hospital stay right after treatment
- Were more likely to have had an emergency room (ER) visit after treatment
- Spent slightly more time in the hospital for complications or to have surgery after treatment
- Missed fewer days of work
Some patients had appendicolith, a hardened deposit within the appendix. For patients treated with antibiotics, those with this condition were more likely to have surgery later compared to patients without the condition. Of the patients with this condition, 41 percent who were treated with antibiotics had surgery within 90 days.
Who was in the study?
The study included 1,552 patients with appendicitis who were receiving care from one of 25 hospitals in 14 states. Of these patients, 60 percent were White, 9 percent were Black, 6 percent were Asian, and 25 percent were another race or multiple races; 47 percent were Hispanic. The average age was 38, and 63 percent were men.
What did the research team do?
The research team assigned patients by chance to receive surgery or antibiotics. At one and three months after treatment, the team called patients to ask about their general health, hospital and ER visits, and the number of days they missed work.
Patients who had appendicitis previously, doctors, policy makers, and health insurers helped design the study.
What were the limits of the study?
About 10 percent of patients didn’t respond to surveys, which may have affected study results. Only 31 percent of patients agreed to be assigned to a treatment by chance. Results may have differed if all patients had agreed to be assigned by chance.
Future research could track patient outcomes longer after treatment with antibiotics or surgery.
How can people use the results?
Patients and their doctors can use the results when considering how to treat appendicitis.
Professional Abstract
Objective
To compare the effectiveness of an appendectomy versus antibiotics in treating appendicitis
Study Design
| Design Element | Description |
|---|---|
| Design | Randomized controlled trial |
| Population | 1,552 patients with imaging-confirmed appendicitis receiving care at 1 of 25 hospitals in 14 states, including patients with appendicolith |
| Interventions/ Comparators |
|
| Outcomes |
Primary: general health status at 30 days posttreatment Secondary: ED visits, hospitalization days, days of missed work |
| Timeframe | 1-month follow-up for primary outcome |
This randomized noninferiority trial compared the effectiveness of an appendectomy versus antibiotics in treating appendicitis 30 days posttreatment.
Researchers randomized patients to receive either an appendectomy or antibiotics. Patients who received antibiotics received them intravenously for one day and orally for nine more days. Researchers called patients 30 and 90 days after treatment to assess their general health status through the EQ-5D, a questionnaire that measures patient-reported mobility, ability to do self-care and daily activities, pain and discomfort, and anxiety and depression. Researchers also surveyed patients about emergency department (ED) visits, number of days in the hospital after initial treatment, and number of missed workdays.
The study included 1,552 patients with imaging-confirmed appendicitis receiving care from one of 25 hospitals in 14 states. Of these patients, 60% were White, 9% were Black, 6% were Asian, and 25% were another race or multiple races; 47% were Hispanic. The average age was 38, and 63% were male.
Patients who had appendicitis previously, clinicians, policy makers, and health insurers helped design the study.
Results
Of randomized patients, 776 received an appendectomy, and 776 received antibiotics.
When measured 30 days posttreatment, health status was no worse for patients randomized to receive antibiotics than for those randomized to receive an appendectomy.
At 90 days, 71% of patients treated with antibiotics had not had an appendectomy. Compared with patients who initially received an appendectomy, patients who received antibiotics:
- Were more likely to be hospitalized after initial treatment (24% versus 5.2%; relative ratio=4.62)
- Were more likely to have an ED visit after treatment (8.9% versus 4.3%; relative ratio=2.07)
- Spent more time in the hospital for complications or to have an appendectomy after initial treatment (0.7 days versus 0.2 days; rate ratio=4.38)
- Missed fewer workdays (5.3 days versus 8.7 days; rate ratio=0.63)
Among patients who received antibiotics, more patients with appendicolith had an appendectomy later compared to patients without appendicolith (41% versus 25%).
Limitations
About 10% of participants did not respond to surveys at 30 days, and only 31% of eligible patients agreed to be randomized to receive an appendectomy or antibiotics, which may have biased the results.
Conclusions and Relevance
In this study, health status was not inferior to patients who received antibiotics than for patients who received an appendectomy. More than 70% of patients who were treated with antibiotics avoided an appendectomy by 90 days. Patients who received antibiotics missed fewer workdays but had higher rates of hospitalization and ED visits than did patients who received an appendectomy.
Future Research Needs
Future research could follow patients to track long-term outcomes after receiving antibiotics or an appendectomy.
Final Research Report
View this project's final research report.
Engagement Resources
More to Explore...
Blogs
(Credit: CODA Study team)
PCORI-Funded Study Examining Treatment Options for Appendicitis Yields Useful Early Results
This PCORI-funded study comparing surgery versus antibiotics for uncomplicated appendicitis released early results that physicians and patients can use when weighing treatment options, especially during the coronavirus pandemic.
Media Mentions
Behind The Knife: The Surgery Podcast (October 5, 2020)
In this episode, Principal Investigator David Reed Flum, MD, MPH, and members of his team discuss the early results of the trial. Listen on Apple Podcasts / Spotify
Study Website
CODA Appendicitis Study
http://codastudy.org/
University of Washington
Related PCORI Dissemination and Implementation Project
Journal Citations
Article Highlight: At least in the short term, using antibiotics to treat appendicitis worked as well as surgical removal of the appendix for most patients in the CODA trial, as reported in the New England Journal of Medicine. Health outcomes associated with each treatment were similar. More than 70 percent of patients on antibiotics avoided having surgery and missed less time away from work or school in the three months post-treatment. However, nearly 30 percent who received antibiotics ultimately needed surgery. CODA was conducted at 25 sites nationwide and involved a wider range of patients than previous studies, making its results more broadly applicable to typical patients with appendicitis.
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers noted that to test the effect of appendicolith status on study outcomes the researchers needed to report on the interaction between the status and the treatment group on the outcomes. In response, the researchers explained that they were not looking at the interaction between appendicolith status and treatment group—they were only interested in the outcomes for patients with an appendicolith because these patients are typically excluded from clinical trials on appendicitis treatment.
- The reviewers questioned the researchers’ approach to their power calculations, which seemed to be focused on differences between treatment groups even though this study was described as a noninferiority comparison. The researchers confirmed that this was a noninferiority study and revised statements in their report to clarify.
- The reviewers asked about the participants who refused randomization and were assigned to a concurrent observational study where participants could choose surgery or medication to treat their appendicitis. The researchers edited the report to clarify that they used inverse probability weighting in the observational sample to account for baseline differences between treatment groups. In addition, the researchers compared the observational cohort after adjusting for baseline differences to the randomized cohort and found similar results for study outcomes.