The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial

2016-06-15 17:53:22 | BioPortfolio


For the past 130 years, appendectomy has been the standard treatment for appendicitis. Recent studies from Europe have challenged the notion that surgery is the best option, showing that antibiotics alone can treat appendicitis without a need for appendectomy in as many as 3 out of 4 patients and without safety issues for up to one year of follow up. Despite these results, it remains to be determined if the antibiotic strategy is as good as an appendectomy for the outcomes that most patients care about. The Patient-Centered Outcomes Research Institute (PCORI)-funded Comparison of Outcomes of Drugs and Appendectomy (CODA) trial will be the first American, and largest-ever randomized trial of the issue and its results should help surgeons and patients make more informed healthcare decisions.


The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial aims to test, if from a patient's perspective, the antibiotics strategy is "just as good as" surgery. The investigators believe that patients, clinicians, and the people who pay for healthcare (both patients and insurers) will find the antibiotics approach acceptable if 1) it results in high rates of treatment success, 2) does not increase complications, and 3) provides an equivalent or better patient experience. A large-scale non-inferiority trial is expected to result in a change in the management of one of the most common human illnesses. If non-inferiority is demonstrated (or superiority of the antibiotics approach identified), that finding will improve patient choice and should support a shift to the less invasive approach. If non-inferiority is not established, results may help to delineate the trade-offs between the two treatment approaches and inform decision-making.

The observation that patients with acute uncomplicated appendicitis (AUA) can be cured with antibiotics-alone has a scientific rationale. Traditionally, appendicitis was thought to result from a blockage of the appendix and that, if left untreated, inevitably led to a perforation. Contrary to this physiologic model, Carr demonstrated that obstruction of the appendix is an unlikely primary cause in the majority of patients and that most are caused by an enteric infection. A recent randomized trial found an increased rate of appendectomy with early use of computed tomography (CT) imaging and diagnostic laparoscopy, but case reports of appendicitis remission documented by serial CT all suggest that leaving the appendix in place does not inexorably lead to clinical compromise. A common concern of clinicians when considering treating AUA with antibiotics is that not removing the appendix may lead to perforation and complications from complicated appendicitis. Evidence suggests, however, that perforated appendicitis is a pre-hospital event and that non-perforated appendicitis is a "different" disease. This theory is supported by a general lack of relation between a delay in surgery of up to 24-36 hours and perforation rates. Most recently, Fusobacterium sp., a genus of enteric Gram-negative anaerobic bacteria, rather than an obstructive stone, was found to be correlated with the presence of appendicitis and the degree of inflammation. What remains to be determined is whether certain bacterial colonies or features of individual immune response are most associated with progression of appendicitis without appendectomy and whether successful outcomes for people undergoing antibiotics can be predicted based on the patient's characteristics.

An additional rationale for this study is to address limitations of prior trials. To avoid misclassification problems of other trials, all patients will undergo standard radiographic imaging including CT, ultrasound (US), or magnetic resonance imaging (MRI). Patients with an appendicolith will be included in the trial but considered a unique subgroup and will be evaluated as part of a pre-specified analysis (potentially excluding them from future recruitment if an early analysis demonstrates futility related to the primary antibiotic approach not being successful). To reflect usual and emerging techniques in treatment, the study includes both types of appendectomy (open and laparoscopic) and a broad range of antibiotic strategies including the option for an "all outpatient" treatment schedule with once daily dosing of longer-acting agents. Patients in the antibiotics arm will be given a minimum of 24 hours of intravenous (IV) antibiotics (using any appropriate dosing schedule and based on the patient's ability to tolerate oral medication), followed by oral antibiotics for a total of 10 days of antibiotic treatment). Discharge from the hospital or emergency department (ED) or a change in treatment arms will be guided by clinical targets and reasons for change in treatment arms will be assessed. Patients will be followed for up to two years to assess for longer-term complications, eventual appendectomy (performed anywhere), quality of life (QoL), gastrointestinal symptoms, and decisional regret. To quantify selection bias and to promote generalizability, all patients approached for the study and those who refuse randomization will be characterized at baseline. A parallel cohort of patients who refuse randomization (250 who initiate the antibiotics strategy and 250 who select the appendectomy strategy) will be surveyed for two years.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment




Cefoxitin, Ertapenem, Moxifloxacin, Tigecycline, Ticarcillin-Clavulanic Acid; Metronidazole plus Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, or Levofloxacin, Appendectomy


Harborview Medical Center
United States




University of Washington

Results (where available)

View Results


Published on BioPortfolio: 2016-06-15T17:53:22-0400

Clinical Trials [1387 Associated Clinical Trials listed on BioPortfolio]

Moxifloxacin Versus Amoxicillin Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis

A study to assess the safety and efficacy of moxifloxacin compared to that of amoxicillin-clavulanic acid for the treatment of subjects with acute exacerbation of chronic bronchitis.

Therapy of Complicated Intra-Abdominal Infections With Moxifloxacin or Ertapenem

A study to compare the safety and efficacy of moxifloxacin to ertapenem in patients with intra-abdominal infections.

Study Evaluating the Safety and Efficacy of a Once-daily Dose of Tigecycline vs Ertapenem in Diabetic Foot Infections (DFI) With a Substudy in Patients With Diabetic Foot Infections Complicated by Osteomyelitis.

The purpose of this study was to look at the safety and effectiveness of a once-daily dose of tigecycline compared to ertapenem for the treatment of diabetic foot infections. The co-prima...

Comparison of Sequential IV/PO Moxifloxacin With IV Piperacillin/Tazobactam Followed by PO Amoxicillin/Clavulanic Acid in Patients With a Complicated Skin and Skin Structure Infection

Patients who are considered suitable by their physicians, to take part in this research, will have a physical examination (including an Electrocardiogram (ECG)), blood and urine samples ta...

Clavulanic Acid (CLAV) and Cocaine Interaction Safety Study

The main purpose of this study is to determine if it is safe to use the study drug, clavulanic acid, in combination with cocaine. In this study, subjects will receive intravenous (i.v.) co...

PubMed Articles [6632 Associated PubMed Articles listed on BioPortfolio]

Orally Absorbed Derivatives of the β-Lactamase Inhibitor Avibactam. Design of Novel Prodrugs of Sulfate Containing Drugs.

There have been several generations of β-lactamase inhibitor (BLI) drugs, but only one of these FDA-approved BLIs has ever been orally available - clavulanic acid, approved in 1984. Avibactam, approv...

Relative Oral Bioavailability of Two Amoxicillin-Clavulanic Acid Formulations in Healthy Dogs: A Pilot Study.

The use of human generic amoxicillin-clavulanic acid formulations in veterinary medicine is currently lacking supportive evidence. This pilot study was conducted to determine preliminary pharmacokinet...

Different influences on mitochondrial function, oxidative stress and cytotoxicity of antibiotics on primary human neuron and cell lines.

Although antibiotics are generally well tolerated, their toxic effects on the central nervous system have been gained attention. In this study, we systematically investigated the neuron toxicity of an...

Does the use of amoxicillin/amoxicillin-clavulanic acid in third molar surgery reduce the risk of postoperative infection? A systematic review with meta-analysis.

The objectives of this systematic review were to investigate the efficacy of amoxicillin/amoxicillin-clavulanic acid for reducing the risk of postoperative infection after third molar surgery and to e...

Mechanisms of Bacteroides fragilis resistance to metronidazole.

Metronidazole-resistant Bacteroides fragilis (B. fragilis) have been reported worldwide. Several mechanisms contribute to B. fragilis resistance to metronidazole. In some cases, the mechanisms of metr...

Medical and Biotech [MESH] Definitions

Clavulanic acid and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase.

Acids, salts, and derivatives of clavulanic acid (C8H9O5N). They consist of those beta-lactam compounds that differ from penicillin in having the sulfur of the thiazolidine ring replaced by an oxygen. They have limited antibacterial action, but block bacterial beta-lactamase irreversibly, so that similar antibiotics are not broken down by the bacterial enzymes and therefore can exert their antibacterial effects.

A semisynthetic cephamycin antibiotic resistant to beta-lactamase.

An antibiotic derived from penicillin similar to CARBENICILLIN in action.

A fixed-ratio combination of amoxicillin trihydrate (see AMOXICILLIN), an aminopenicillin, and potassium clavulanate (see CLAVULANIC ACID), a beta-lactamase inhibitor, used to treat a broad-spectrum of bacterial infections, especially resistant strains.

More From BioPortfolio on "The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial"

Quick Search


Relevant Topics

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Health care (or healthcare) is the diagnosis, treatment, and prevention of disease, illness, injury, and other physical and mental impairments in humans. Health care is delivered by practitioners in medicine, chiropractic, dentistry, nursing, pharmacy, a...

Searches Linking to this Trial