Low vs. Standard Dose CT for Appendicitis Trial

Study Overview
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Brief Summary
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To determine whether low-dose (LD) CT is noninferior to standard-dose (SD) computed tomography (CT) as the first-line imaging test in adolescents and young adults in regard to negative appendectomy rate (NAR).

Detailed Description
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Acute appendicitis is a very common disease. Many patients are adolescents or young adults. CT is the current standard imaging test for the diagnosis of appendicitis. In recent years, the awareness of carcinogenic risk associated with CT radiation has increased. According to a recent single-institutional randomized controlled trial, LD CT (employing a quarter of standard radiation dose) was found to be noninferior to SD CT with respect to NARs in adolescents and young adults with suspected appendicitis. However, LD CT is not yet widely accepted. To establish LD CT as the first-line imaging test, a multi-institutional study is needed to confirm the generalizability of the prior single-institutional study.

Official Title
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A Multi-institutional Trial Comparing Clinical Outcomes Following Low- vs. Standard-dose Abdominal CT as the First-line Imaging Test in Adolescents and Young Adults With Suspected Acute Appendicitis

Conditions
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Appendicitis

Intervention / Treatment
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* Diagnostic Test: Diagnostic CT with low-dose radiation
* Diagnostic Test: Diagnostic CT with standard-dose radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Emergency department visit with suspected symptoms and signs of acute appendicitis Intravenous contrast-enhanced computed tomography examination requested due to suspicion of appendicitis Willing to provide telephone or cell phone numbers for follow-up Signed informed consent provided prior to study entry Exclusion Criteria: Prior cross-sectional imaging tests to evaluate the presenting symptoms and signs Prior history of surgical removal of the appendix

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose CT<br>Diagnostic CT with low-dose radiation | Diagnostic Test: Diagnostic CT with low-dose radiation<br>* Effective dose is aimed at approximately 2 millisievert (mSv) in an average patient.<br>* Other names: Low-dose CT;|
| Active Comparator: Standard-dose CT<br>Diagnostic CT with standard-dose radiation | Diagnostic Test: Diagnostic CT with standard-dose radiation<br>* Effective dose is aimed at approximately 8 millisievert (or less) in an average patient.<br>* Other names: Standard-dose CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative Appendectomy Rate | Negative appendectomy rate was defined as the percentage of negative (unnecessary) appendectomies among all non-incidental appendectomies. As a secondary analysis, negative appendectomy rate in an alternative definition was calculated by excluding cases with appendiceal neoplasms without superimposed appendicitis, as appendectomy would be clinically necessary in such patients. Any surgery performed for the treatment of presumed appendicitis was counted as non-incidental appendectomy, even though the surgical procedures were more extensive than simple appendectomy (e.g., ileocectomy). | 1 week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appendiceal Perforation Rate | The percentage of perforated appendicitis among confirmed appendicitis cases. | 1 week after surgery | 
| Number of Appendectomies | Appendectomy rate. The percentage of appendectomies among all randomized cases. | 3 months after CT | 
| Number of Negative Appendectomies | The percentage of negative appendectomies among all randomized cases. In January, 2016, when more than 2000 patients were enrolled, the data and safety monitoring board noted a between-group imbalance in the number of appendectomies. Because of the concern that such an imbalance might potentially jeopardize the comparability for the prespecified endpoints, the study protocol was amended to adopt the following additional secondary endpoints, which were assessed among all randomly assigned patients: the number of appendectomies, number of negative appendectomies, prevalence of perforated appendicitis, and prevalence of non-perforated appendicitis. | 1 week after surgery | 
| Prevalence of Perforated Appendicitis | The percentage (i.e., prevalence) of perforated appendicitis among all randomized cases. In January, 2016, when more than 2000 patients were enrolled, the data and safety monitoring board noted a between-group imbalance in the number of appendectomies. Because of the concern that such an imbalance might potentially jeopardize the comparability for the prespecified endpoints, the study protocol was amended to adopt the following additional secondary endpoints, which were assessed among all randomly assigned patients: the number of appendectomies, number of negative appendectomies, prevalence of perforated appendicitis, and prevalence of non-perforated appendicitis. | 1 week after surgery | 
| Prevalence of Non-perforated Appendicitis | The percentage (i.e., prevalence) of non-perforated appendicitis among all randomized cases. In January, 2016, when more than 2000 patients were enrolled, the data and safety monitoring board noted a between-group imbalance in the number of appendectomies. Because of the concern that such an imbalance might potentially jeopardize the comparability for the prespecified endpoints, the study protocol was amended to adopt the following additional secondary endpoints, which were assessed among all randomly assigned patients: the number of appendectomies, number of negative appendectomies, prevalence of perforated appendicitis, and prevalence of non-perforated appendicitis. | 1 week after surgery | 
| Need for Additional Imaging Test(s) | The proportion of patients requiring additional imaging test(s) in order to diagnose or rule out appendicitis. | 1 week after CT | 
| Delay in Patient Disposition | The interval from CT acquisition to appendectomy in patients undergoing appendectomy. Interval appendectomies following percutaneous abscess drainage and/or medical treatment were not included in this analysis. The interval from CT acquisition to hospital discharge in patients not undergoing surgery. | 3 months after CT | 
| Length of Hospital Stay Associated With Appendectomy | The interval from CT acquisition to hospital discharge after appendectomy. | 3 months after CT | 
| Diagnostic Performance of CT Reports - AUC | - Area under the receiver-operating-characteristic curve (AUC). | 3 months after CT | 
| Diagnostic Performance of CT Reports - Sensitivity and Specificity | Diagnostic sensitivity and specificity: the 5-grade likelihood scores for appendicitis were collapsed into binary responses with a decision threshold of a score ≥ 3 as positive for the diagnosis. Sensitivity is a proportion of the positive test among the patient confirmed as having appendicitis. Specificity is a proportion of the negative test among the patient confirmed as not having appendicitis. | 3 months after CT | 
| Diagnostic Confidence in Diagnosing and Ruling Out Appendicitis: Likelihood Score for Appendicitis | Likelihood score for appendicitis in patients confirmed as having appendicitis. Likelihood score for appendicitis in patients confirmed as not having appendicitis. Grade 1 denotes appendicitis definitely absent; grade 2, appendicitis probably absent; grade 3, indeterminate for the presence of appendicitis; grade 4, appendicitis probably present; and grade 5, appendicitis definitely present. | 3 months after CT | 
| Diagnostic Confidence in Diagnosing and Ruling Out Appendicitis: Indeterminate Interpretation (Grade 3) | The frequency of indeterminate CT interpretation (grade 3). Grade 1 denotes appendicitis definitely absent; grade 2, appendicitis probably absent; grade 3, indeterminate for the presence of appendicitis; grade 4, appendicitis probably present; and grade 5, appendicitis definitely present. | 3 months after CT | 
| Diagnostic Confidence in Ruling Out Appendicitis: Normal Appendix Visualization | The frequency of normal appendix visualization at CT. Grade 0 denotes appendix not identified; grade 1, unsure or partly visualized; and grade 2, clearly and entirely visualized. | 3 months after CT | 
| Diagnosis of Appendiceal Perforation at CT | Diagnostic sensitivity: the number of correct detections of the perforation divided by the number of cases of perforated appendicitis. Diagnostic specificity: the number of correct ruling out the perforation divided by the number of cases of appendicitis without perforation. | 3 months after CT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Appendectomy, Appendicitis, False Positive Reactions, Humans, Radiation Dosage, Tomography, X-Ray Computed, Young Adult