Appendicitis
Conditions
Brief summary
The purpose of this study is to determine whether low-dose CT is not inferior to standard-dose CT in the rate of unnecessary appendectomy.
Detailed description
Acute appendicitis is a very common disease with the lifetime incidence of 7%. Abdomen CT is an established first-line diagnostic test in patients suspected of having acute appendicitis. Since many individuals suspected of having acute appendicitis are young, with a mean age of 30 years, CT radiation is of particular concern. The estimated lifetime attributable risk of death from cancer due to the radiation exposure of a single abdomen CT study is 2-7/10,000 for average adults ranging 20-40 years in age. The purpose of this study is to determine whether low-dose CT is not inferior to standard-dose CT in the negative appendectomy rate.
Interventions
RADIATIONDiagnostic CT
2 mSv in an average patient (Low-dose (1/4 to 1/5 of standard-dose))
Sponsors
GE Healthcare
National Research Foundation of Korea
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
15 Years to 44 Years
Healthy volunteers
No
Inclusion criteria
* Suspected of having acute appendicitis * Referred for abdomen CT from Emergency Department
Exclusion criteria
* Body mass index \< 18.5 kg/m2 (ultrasonography is favored) * Intravenous contrast-enhancement is contraindicated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Negative Appendectomy | 1 week after surgery | Number of participants with unnecessary appendectomies (removal of un-inflamed appendix) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional Imaging Test(s) | 1 week after CT | Number of participants who need additional imaging test(s) to diagnose or rule out appendicitis |
| Appendiceal Perforation | 1 week after surgery | Number of participants with appendiceal perforation |
| Interval Between CT and Appendectomy | 1 day after surgery | Time interval between the CT acquisition and non-incidental appendectomy |
| Interval Between CT and Discharge Without Surgery | 3 months after CT | Time interval between the CT acquisition and discharge without surgery |
| Interval From CT to Discharge After Appendectomy | 3 months after CT | Time interval between the CT acquisition and discharge after appendectomy |
| Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | 3 months after CT | True positive: Perforation was rated as present in CT report and confirmed as present. False positive: Perforation was rated as present in CT report and confirmed as absent. True negative: Perforation was rated as absent in CT report and confirmed as absent. False negative: Perforation was rated as absent in CT report and confirmed as present. The data are used to calculate sensitivity and specificity. |
| Visualization of the Normal Appendix | 3 months after CT | Grade 0. Not identified Grade 1. Unsure or partly visualized Grade 2. Clearly and entirely visualized |
| Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | 3 months after CT | Grade 1. Definitely absent. Clinical observation is recommended. Grade 2. Probably absent. Clinical observation is recommended. Grade 3. Indeterminate. Clinical observation or surgical exploration is recommended. Grade 4. Probably present. Surgical exploration is recommended. Grade 5. Definitely present. Surgical exploration is recommended. The data is used to calculate sensitivity, specificity, area under receiver-operating-curve and to measure diagnostic confidence. |
| Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | 3 months after CT | Grade 1. Definitely absent. Clinical observation is recommended. Grade 2. Probably absent. Clinical observation is recommended. Grade 3. Indeterminate. Clinical observation or surgical exploration is recommended. Grade 4. Probably present. Surgical exploration is recommended. Grade 5. Definitely present. Surgical exploration is recommended. The data are used to calculate sensitivity, specificity, area under receiver-operating-curve and to measure diagnostic confidence. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Radiation Dose | 1 day after CT | Radiation dose is measured in terms of dose-length product (mGy•cm) as displayed in the CT console. The length indicates the scan range. |
| Estimate of Carcinogenic Risk Induced by CT Radiation | 1 day after CT | Age- and sex-specific carcinogenic risk induced by CT radiation. This is not an actual measurement but an estimate of the stochastic risk, based on assumption and calculation from radiation dose used. |
Countries
South Korea
Participant flow
Recruitment details
Dates of the recruitment period: September 2009 to January 2011 Types of location: an emergency department in an urban tertiary hospital in Korea
Pre-assignment details
None of the enrolled participants were excluded from the trial before assignment to group.
Participants by arm
| Arm | Count |
|---|---|
| Low-dose CT Aimed to 2 mSv in an average patient | 444 |
| Standard-dose CT Aimed to 8 mSv in an average patient | 447 |
| Total | 891 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Clinical Outcomes | Lost to Follow-up | 6 | 6 |
Baseline characteristics
| Characteristic | Standard-dose CT | Total | Low-dose CT |
|---|---|---|---|
| Age Continuous Age (year) | 30 year | 30 year | 29 year |
| Body mass index 18.5-24.9 (normal) | 301 kg/m^2 | 613 kg/m^2 | 312 kg/m^2 |
| Body mass index < 18.5 (underweight) | 60 kg/m^2 | 122 kg/m^2 | 62 kg/m^2 |
| Body mass index ≥ 25.0 (overweight to extremely obese) | 86 kg/m^2 | 156 kg/m^2 | 70 kg/m^2 |
| C-reactive protein | 0.7 mg/dL | 0.6 mg/dL | 0.5 mg/dL |
| CT scanner 16-detector CT | 191 participants | 368 participants | 177 participants |
| CT scanner 256-detector CT | 112 participants | 225 participants | 113 participants |
| CT scanner 64-detector CT | 144 participants | 298 participants | 154 participants |
| Race/Ethnicity, Customized Korean | 445 participants | 886 participants | 441 participants |
| Race/Ethnicity, Customized Non-Korean | 2 participants | 5 participants | 3 participants |
| Radiologist Abdominal radiologist | 225 participants | 442 participants | 217 participants |
| Radiologist Non-abdominal radiologist | 222 participants | 449 participants | 227 participants |
| Segmented neutrophil | 77.3 Percentage of peripheral Leukocytes | 77.3 Percentage of peripheral Leukocytes | 77.0 Percentage of peripheral Leukocytes |
| Sex: Female, Male Female | 263 Participants | 539 Participants | 276 Participants |
| Sex: Female, Male Male | 184 Participants | 352 Participants | 168 Participants |
| White blood cell | 10.8 x10^3/mm^3 | 10.8 x10^3/mm^3 | 10.7 x10^3/mm^3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 444 | 1 / 447 |
| serious Total, serious adverse events | 13 / 444 | 11 / 447 |
Outcome results
Primary
Negative Appendectomy
Number of participants with unnecessary appendectomies (removal of un-inflamed appendix)
Time frame: 1 week after surgery
Population: Participants who underwent non-incidental appendectomy. Intention to treat. Complete case analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Negative Appendectomy | Negative appendectomy | 6 participants |
| Low-dose CT | Negative Appendectomy | Not negative appendectomy | 166 participants |
| Standard-dose CT | Negative Appendectomy | Negative appendectomy | 6 participants |
| Standard-dose CT | Negative Appendectomy | Not negative appendectomy | 180 participants |
Secondary
Additional Imaging Test(s)
Number of participants who need additional imaging test(s) to diagnose or rule out appendicitis
Time frame: 1 week after CT
Population: All participants included in outcome analyses. Intention to treat. Complete case analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Additional Imaging Test(s) | Additional imaging | 14 participants |
| Low-dose CT | Additional Imaging Test(s) | No additional imaging | 424 participants |
| Standard-dose CT | Additional Imaging Test(s) | Additional imaging | 7 participants |
| Standard-dose CT | Additional Imaging Test(s) | No additional imaging | 434 participants |
Secondary
Appendiceal Perforation
Number of participants with appendiceal perforation
Time frame: 1 week after surgery
Population: Participants confirmed to have appendicitis. Intention to treat. Complete case analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Appendiceal Perforation | Perforation | 44 participants |
| Low-dose CT | Appendiceal Perforation | No perforation | 122 participants |
| Standard-dose CT | Appendiceal Perforation | Perforation | 42 participants |
| Standard-dose CT | Appendiceal Perforation | No perforation | 138 participants |
Secondary
Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis.
True positive: Perforation was rated as present in CT report and confirmed as present. False positive: Perforation was rated as present in CT report and confirmed as absent. True negative: Perforation was rated as absent in CT report and confirmed as absent. False negative: Perforation was rated as absent in CT report and confirmed as present. The data are used to calculate sensitivity and specificity.
Time frame: 3 months after CT
Population: Participants confirmed to have appendicitis. Intention to treat. Complete case analysis.~There can be missing data if CT report was not made following predefined structured format.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | Missing | 1 participants |
| Low-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | True positive | 16 participants |
| Low-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | False positive | 11 participants |
| Low-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | True negative | 110 participants |
| Low-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | False negative | 28 participants |
| Standard-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | False negative | 19 participants |
| Standard-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | True negative | 121 participants |
| Standard-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | True positive | 23 participants |
| Standard-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | Missing | 0 participants |
| Standard-dose CT | Diagnosis of Appendiceal Perforation in CT in Patients With Confirmed Appendicitis. | False positive | 17 participants |
Secondary
Interval Between CT and Appendectomy
Time interval between the CT acquisition and non-incidental appendectomy
Time frame: 1 day after surgery
Population: Participants who underwent non-incidental appendectomy. Intention to treat. Complete case analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-dose CT | Interval Between CT and Appendectomy | 7.1 hr |
| Standard-dose CT | Interval Between CT and Appendectomy | 5.6 hr |
Secondary
Interval Between CT and Discharge Without Surgery
Time interval between the CT acquisition and discharge without surgery
Time frame: 3 months after CT
Population: Participants who did not undergo surgery. Intention to treat. Complete case analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-dose CT | Interval Between CT and Discharge Without Surgery | 2.5 hr |
| Standard-dose CT | Interval Between CT and Discharge Without Surgery | 2.4 hr |
Secondary
Interval From CT to Discharge After Appendectomy
Time interval between the CT acquisition and discharge after appendectomy
Time frame: 3 months after CT
Population: Participants who underwent non-incidental appendectomy. Intention to treat. Complete case analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-dose CT | Interval From CT to Discharge After Appendectomy | 3.4 day |
| Standard-dose CT | Interval From CT to Discharge After Appendectomy | 3.2 day |
Secondary
Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis
Grade 1. Definitely absent. Clinical observation is recommended. Grade 2. Probably absent. Clinical observation is recommended. Grade 3. Indeterminate. Clinical observation or surgical exploration is recommended. Grade 4. Probably present. Surgical exploration is recommended. Grade 5. Definitely present. Surgical exploration is recommended. The data is used to calculate sensitivity, specificity, area under receiver-operating-curve and to measure diagnostic confidence.
Time frame: 3 months after CT
Population: Participants confirmed to have appendicitis. Intention to treat. Complete case analysis.~There can be missing data if CT report was not made following predefined structured format.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 1 | 2 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 2 | 7 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 3 | 13 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 4 | 53 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 5 | 90 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Missing | 1 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 5 | 126 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 1 | 4 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 4 | 34 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 2 | 5 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Missing | 0 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Having Appendicitis | Grade 3 | 11 participants |
Secondary
Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis
Grade 1. Definitely absent. Clinical observation is recommended. Grade 2. Probably absent. Clinical observation is recommended. Grade 3. Indeterminate. Clinical observation or surgical exploration is recommended. Grade 4. Probably present. Surgical exploration is recommended. Grade 5. Definitely present. Surgical exploration is recommended. The data are used to calculate sensitivity, specificity, area under receiver-operating-curve and to measure diagnostic confidence.
Time frame: 3 months after CT
Population: Participants confirmed not to have appendicitis. Intention to treat. Complete case analysis.~There can be missing data if CT report was not made following predefined structured format.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 1 | 185 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 2 | 65 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 3 | 11 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 4 | 3 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 5 | 4 participants |
| Low-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Missing | 4 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 5 | 2 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 1 | 206 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 4 | 3 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 2 | 38 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Missing | 1 participants |
| Standard-dose CT | Likelihood of Appendicitis in CT Report in Patients Confirmed as Not Having Appendicitis | Grade 3 | 11 participants |
Secondary
Visualization of the Normal Appendix
Grade 0. Not identified Grade 1. Unsure or partly visualized Grade 2. Clearly and entirely visualized
Time frame: 3 months after CT
Population: Participants confirmed not to have appendicitis. Intention to treat. Complete case analysis.~There can be missing data if CT report was not made following predefined structured format.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose CT | Visualization of the Normal Appendix | Grade 0 | 18 participants |
| Low-dose CT | Visualization of the Normal Appendix | Grade 1 | 41 participants |
| Low-dose CT | Visualization of the Normal Appendix | Grade 2 | 209 participants |
| Low-dose CT | Visualization of the Normal Appendix | Missing | 4 participants |
| Standard-dose CT | Visualization of the Normal Appendix | Missing | 1 participants |
| Standard-dose CT | Visualization of the Normal Appendix | Grade 0 | 13 participants |
| Standard-dose CT | Visualization of the Normal Appendix | Grade 2 | 227 participants |
| Standard-dose CT | Visualization of the Normal Appendix | Grade 1 | 20 participants |
Other Pre-specified
Estimate of Carcinogenic Risk Induced by CT Radiation
Age- and sex-specific carcinogenic risk induced by CT radiation. This is not an actual measurement but an estimate of the stochastic risk, based on assumption and calculation from radiation dose used.
Time frame: 1 day after CT
Other Pre-specified
Radiation Dose
Radiation dose is measured in terms of dose-length product (mGy•cm) as displayed in the CT console. The length indicates the scan range.
Time frame: 1 day after CT
Population: All participants who underwent CT. Intention to treat. Complete case analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-dose CT | Radiation Dose | 116 mGy•cm |
| Standard-dose CT | Radiation Dose | 521 mGy•cm |