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Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

ABSTRACT: INTRODUCTION:Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy. OBJECTIVES:The Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy. METHODS/ANALYSIS:CODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4?weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm. ETHICS AND DISSEMINATION:This trial was approved by the University of Washington's Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:NCT02800785.

SUBMITTER: Davidson GH

PROVIDER: S-EPMC5695382 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

Davidson Giana H GH Flum David R DR Talan David A DA Kessler Larry G LG Lavallee Danielle C DC Bizzell Bonnie J BJ Farjah Farhood F Stewart Skye D SD Krishnadasan Anusha A Carney Erin E EE Wolff Erika M EM Comstock Bryan A BA Monsell Sarah E SE Heagerty Patrick J PJ Ehlers Annie P AP DeUgarte Daniel A DA Kaji Amy H AH Evans Heather L HL Yu Julianna T JT Mandell Katherine A KA Doten Ian C IC Clive Kevin S KS McGrane Karen M KM Tudor Brandon C BC Foster Careen S CS Saltzman Darin J DJ Thirlby Richard C RC Lange Erin O EO Sabbatini Amber K AK Moran Gregory J GJ

BMJ open 20171115 11

<h4>Introduction</h4>Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficien ...[more]

PMID: 29146633

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Project description:ImportanceAntibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial.ObjectiveTo compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients.Data sourcesThe PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial.Study selectionRandomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days.Data extraction and synthesisData were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated.Main outcomes and measuresThe primary outcome was the success rate of treatment. The hypothesis was formulated before data collection.ResultsA total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P?=?.99; I2?=?0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity, P?=?.91; I2?=?0%).Conclusions and relevanceThis meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith.

Project description:BACKGROUND:Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis. METHODS:APPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients. Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin. DISCUSSION:To our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis. TRIAL REGISTRATION:Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.

Project description:Background:Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods:Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5-16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12?hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48?hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1?year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion:The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number:clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016.

Project description:Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial.The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point.The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

Project description:Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days.Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ? 0.025). Both per-protocol and intention-to-treat analyses will be performed.This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly.Dutch Trial Register, NTR6128 . Registered on 20 December 2016.

Project description:ImportanceUse of antibiotics for the treatment of appendicitis is safe and has been found to be noninferior to appendectomy based on self-reported health status at 30 days. Identifying patient characteristics associated with a greater likelihood of appendectomy within 30 days in those who initiate antibiotics could support more individualized decision-making.ObjectiveTo assess patient factors associated with undergoing appendectomy within 30 days of initiating antibiotics for appendicitis.Design, setting, and participantsIn this cohort study using data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial, characteristics among patients who initiated antibiotics were compared between those who did and did not undergo appendectomy within 30 days. The study was conducted at 25 US medical centers; participants were enrolled between May 3, 2016, and February 5, 2020. A total of 1552 participants with acute appendicitis were randomized to antibiotics (776 participants) or appendectomy (776 participants). Data were analyzed from September 2020 to July 2021.ExposuresAppendectomy vs antibiotics.Main outcomes and measuresConditional logistic regression models were fit to estimate associations between specific patient factors and the odds of undergoing appendectomy within 30 days after initiating antibiotics. A sensitivity analysis was performed excluding participants who underwent appendectomy within 30 days for nonclinical reasons.ResultsOf 776 participants initiating antibiotics (mean [SD] age, 38.3 [13.4] years; 286 [37%] women and 490 [63%] men), 735 participants had 30-day outcomes, including 154 participants (21%) who underwent appendectomy within 30 days. After adjustment for other factors, female sex (odds ratio [OR], 1.53; 95% CI, 1.01-2.31), radiographic finding of wider appendiceal diameter (OR per 1-mm increase, 1.09; 95% CI, 1.00-1.18), and presence of appendicolith (OR, 1.99; 95% CI, 1.28-3.10) were associated with increased odds of undergoing appendectomy within 30 days. Characteristics that are often associated with increased risk of complications (eg, advanced age, comorbid conditions) and those clinicians often use to describe appendicitis severity (eg, fever: OR, 1.28; 95% CI, 0.82-1.98) were not associated with odds of 30-day appendectomy. The sensitivity analysis limited to appendectomies performed for clinical reasons provided similar results regarding appendicolith (adjusted OR, 2.41; 95% CI, 1.49-3.91).Conclusions and relevanceThis cohort study found that presence of an appendicolith was associated with a nearly 2-fold increased risk of undergoing appendectomy within 30 days of initiating antibiotics. Clinical characteristics often used to describe severity of appendicitis were not associated with odds of 30-day appendectomy. This information may help guide more individualized decision-making for people with appendicitis.

Project description:Introduction Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation. Methods and analysis We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings. Ethics and dissemination The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals. Trial registration number NCT04468321

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Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

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Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

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