Low vs. Standard Dose CT for Appendicitis Trial (LOCAT)

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

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).

Study Overview

• Status: Completed
• Conditions: Appendicitis
• Intervention / Treatment: Diagnostic test: Diagnostic CT with low-dose radiation; Diagnostic test: Diagnostic CT with standard-dose radiation

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Actual): 3074
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 700-712
    • Keimyung University Dongsan Medical Center
  • Gwangju, Korea, Republic of, 501-757
    • Chonnam National University Hospital
  • Iksan, Korea, Republic of, 570-711
    • Wonkwang University School of Medicine & Hospital
  • Incheon, Korea, Republic of, 405-760
    • Gachon University Gil Medical Center
  • Jeju City, Korea, Republic of, 690-767
    • Jeju National University Hospital
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 156-755
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of, 152-703
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of, 150-950
    • Hallym University Kangnam Sacred Heart Hospital
  • Seoul, Korea, Republic of, 110-746
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 137-701
    • The Catholic University of Korea, College of Medicine, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 140-887
    • Soonchunhyang University Seoul Hospital
  • Gangwon
    • Chuncheon, Gangwon, Korea, Republic of, 200-722
      • Kangwon National University Hospital
  • Gyeonggi
    • Ansan, Gyeonggi, Korea, Republic of, 425-707
      • Korea University Ansan Hospital
    • Anyang, Gyeonggi, Korea, Republic of, 431-070
      • Hallym University Sacred Heart Hospital
    • Bucheon, Gyeonggi, Korea, Republic of, 420-767
      • Soonchunhyang University Bucheon Hospital
    • Sanbon, Gyeonggi, Korea, Republic of, 435-040
      • Wonkwang University Sanbon Hospital
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
    • Seongnam, Gyeonggi, Korea, Republic of, 463-774
      • Daejin Medical Center, Bundang Jesaeng General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 44 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low-dose CT; Diagnostic CT with low-dose radiation	Diagnostic test: Diagnostic CT with low-dose radiation; Effective dose is aimed at approximately 2 millisievert (mSv) in an average patient.; Other Names: Low-dose CT
ACTIVE_COMPARATOR: Standard-dose CT; Diagnostic CT with standard-dose radiation	Diagnostic test: Diagnostic CT with standard-dose radiation; Effective dose is aimed at approximately 8 millisievert (or less) in an average patient.; Other Names: Standard-dose CT

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyoung Ho Lee, MD
• Collaborators: Seoul National University Bundang Hospital; Ministry of Health & Welfare, Korea; Radiology Imaging Network of Korea for Clinical Research; The LOCAT Group
• Investigators: Study Chair: Kyoung Ho Lee, MD, Seoul National University Bundang Hospital; Study Director: Kyuseok Kim, MD, Seoul National University Bundang Hospital

Publications and helpful links

General Publications

• Kim K, Kim YH, Kim SY, Kim S, Lee YJ, Kim KP, Lee HS, Ahn S, Kim T, Hwang SS, Song KJ, Kang SB, Kim DW, Park SH, Lee KH. Low-dose abdominal CT for evaluating suspected appendicitis. N Engl J Med. 2012 Apr 26;366(17):1596-605. doi: 10.1056/NEJMoa1110734.
• Ahn S; LOCAT group. LOCAT (low-dose computed tomography for appendicitis trial) comparing clinical outcomes following low- vs standard-dose computed tomography as the first-line imaging test in adolescents and young adults with suspected acute appendicitis: study protocol for a randomized controlled trial. Trials. 2014 Jan 17;15:28. doi: 10.1186/1745-6215-15-28.
• Ko Y, Choi JW, Kim DH, Lee KJ, Shin SS, Woo JY, Cho SW, Kim BS, Lee KH. Central image archiving and management system for multicenter clinical studies: lessons from low-dose CT for appendicitis trial. J Korean Soc Radiol. 2017 Mar 28;76(3):165-72. doi: 10.3348/jksr.2017.76.3.165.
• Yang HK, Ko Y, Lee MH, Woo H, Ahn S, Kim B, Pickhardt PJ, Kim MS, Park SB, Lee KH; Low-Dose CT for Appendicitis Trial (LOCAT) Group. Initial Performance of Radiologists and Radiology Residents in Interpreting Low-Dose (2-mSv) Appendiceal CT. AJR Am J Roentgenol. 2015 Dec;205(6):W594-611. doi: 10.2214/AJR.15.14513. Erratum In: AJR Am J Roentgenol. 2016 Apr;206(4):901. multiple investigator names added.
• Kim HY, Lee S, Kim DH, Ko Y, Park JH, Ko A, Jeong SM, Park SB, Lee KH; LOCAT Group. Conventional-Dose CT Versus 2-mSv CT for Right Colonic Diverticulitis as an Alternate Diagnosis of Appendicitis: Secondary Analysis of Large Pragmatic Randomized Trial Data. AJR Am J Roentgenol. 2021 Nov;217(5):1113-1121. doi: 10.2214/AJR.21.25584. Epub 2021 Apr 7.
• LOCAT Group. Low-dose CT for the diagnosis of appendicitis in adolescents and young adults (LOCAT): a pragmatic, multicentre, randomised controlled non-inferiority trial. Lancet Gastroenterol Hepatol. 2017 Nov;2(11):793-804. doi: 10.1016/S2468-1253(17)30247-9. Epub 2017 Sep 12.

Helpful Links

• LOCAT-Training, a self-learning course to train the radiologists at all Sites to ensure the safety of the participants.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2013
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: August 15, 2013
• First Submitted That Met QC Criteria: August 16, 2013
• First Posted (ESTIMATE): August 19, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Humans; Tomography, X-Ray Computed; Appendicitis; Appendectomy; Young Adult; False Positive Reactions; Radiation Dosage
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis
• Other Study ID Numbers: LOCAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The LOCAT Group has an active standpoint for sharing the LOCAT data, which is in line with the proposal from the International Committee of Medical Journal Editors. The LOCAT Group will share de-identified individual-participant data underlying the main LOCAT results no later than 6 months after the publication of the results. The data will be kept in a publicly available website and freely available to anyone upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No