Study setting {9}
This study protocol is a multi-center, RCT that will be conducted at three academic hospitals and one public hospital in Daegu, Korea. Participants will be recruited from the patients diagnosed with acute appendicitis in Yeungnam University Medical Center, Dongsan Medical Center, Daegu Catholic University Medical Center and Pohang Medical Center.
Eligibility criteria {10}
Inclusion criteria
Patients 19-75 years of age diagnosed with acute appendicitis who will receive a laparoscopic appendectomy will be recruited.
Exclusion criteria
Patients who have one or more of the following will be excluded from this study: (1) patients with a suspected abscess or appendiceal perforation; (2) patients with symptoms of pan-peritonitis symptom; (3) patients with a history of major abdominal surgery; (4) patients who have an inability to express themselves due to conditions such as dementia or intellectual disability; (5) patients with chronic pain who need to take analgesics; (6) patients with severe medical disease such as pulmonary, cardiovascular, hepatic, or renal insufficiency ; (7) Pregnancy; and (8) patients unable to provide consent.
Who will take informed consent? {26a}
The investigating study member in each hosptals is responsible for obtaining written, informed consent from the participant. The consent form must be signed before randomization.
Additional consent provisions for collection and use of participant data and biological specimens {26b}
On the consent form, participants will be asked if they agree to use of their data. Participants will also be asked for permission for the research team to share relevant data. This trial does not involve collecting biological specimens for storage.
Interventions
Explanation for the choice of comparators {6b}
The two choices of comparators include, CLA is performed via a conventional 3-port laparoscopic appendectomy and SILA is performed laparoscopic appendectomy using a single-incision at the umbilicus.
Intervention description {11a}
SILA (Fig. 2A.)
A single 2cm incision will be made at the umbilical area and a custom multi-channel single port (Octoport, Dalim company, Co. Ltd., Korea) will be inserted into the incision site. There will be no restrictions placed on the type of laparoscopic instruments used, and all such decisions will be left to the discretion of the surgeon. The mesoappendix and appendiceal artery will be ligated and resected with an energy device or bipolar cauterization. The appendiceal base will be ligated with a loop tie or clip as per the surgeon’s preference. After the appendectomy, the facia will be closed with an absorbable suture and the skin will be closed using a nylon suture, an absorbable subcuticular suture, or a topical skin adhesive as per the surgeon’s preference.
Additional port insertion or conversion to an open surgery will be possible at the surgeon’s discretion to ensure patient safety.
CLA (Fig. 2B)
A standard three-trocar technique will be used with incisions made at the peri-umbilical, left lower quadrant, and supra-pubic sites. All other techniques for the appendectomy will be similar to those used in the SILA procedure.
Criteria for discontinuing or modifying allocated interventions {11b}
Criteria for discontinuing or modifying include: (1) Participant requests to quit the study after allocation. (2) The main outcome is not recorded or incomplete, which will affect further statistical analysis. Also, Conversion to multiport or open surgery will be possible at the surgeon’s discretion if the patient’s safety is threatened by surgical difficulties, such as severe adhesion, generalized peritonitis or intraoperative complications. In these cases, we will describe the reasons for the conversion.
Strategies to improve adherence to interventions {11c}
Not applicable, this trial does not have strategies to improve adherence.
Relevant concomitant care permitted or prohibited during the trial {11d}
Not applicable, this trial does not have concomitant care permitted or prohibited.
Provisions for post-trial care {30}
Not applicable, once the study is completed, the effect of interventions is minimal.
Outcomes {12}
The primary trial endpoint is cosmetic satisfaction at 6 weeks after surgery as measured by POSAS. The secondary endpoints are cosmetic satisfaction assessed via BIQ, pain assessed via the IPO questionnaire and VAS, and the presence of general postoperative complications.
Baseline characteristics
Baseline demographics for each participant such as age, sex, body mass index, medical history, etc. will be obtained prior to surgery but after informed consent is given.
Perioperative findings
Intraoperative findings including operative time, estimated blood loss, incision length, intraperitoneal findings, method of appendiceal base ligation, additional port insertion, conversion to open appendectomy, and skin suture technique will be recorded. Postoperative analgesics use, hospital stay, and morbidities within 30 days after surgery will be also collected.
PROMs for postoperative pain
VAS and IPO will be used for comparing postoperative pain between treatment groups. VAS will be obtained 6 hours after surgery, as well as on the morning of postoperative day 1 and 2. IPO will be obtained on postoperative day 1.
PROMs for cosmetic satisfaction
POSAS and BIQ will be obtained 6 weeks after surgery in the outpatient clinic. If any participant is unable to attend the clinic, a telephone interview will be permitted for completion of the survey.
Participant timeline {13}
Participant timeline is presented in Fig 3.
Sample size {14}
The target sample size will be 120 participants, as this will provide 80% power at the 2.5% (two-sided) level of significance to detect a three-point difference in the POSAS score between the SILA group and the CLA group at 6 weeks after surgery. Our target sample size allows for 10% attrition.
Recruitment {15}
All candidate patients diagnosed with acute appendicitis will be recruited in the trial. Based on the incidence of acute appendicitis and average amount of the patients in emergency department, the investigators have confidence to recruit enough subjects as planned.
Assignment of interventions: allocation
Sequence generation {16a}
All participants will be randomized to either the SILA group or the CLA group in a 1:1 ratio. The randomization allocation will occur just to surgery using a computerized randomization system.
Concealment mechanism {16b}
Allocation numbers and related information are concealed in sequentially numbered, opaque, sealed envelope. Interventions are assigned to the enrolled participants according to the sequence.
Implementation {16c}
The central registry of the surgical department of Dongsan Medical Center, School of Medicine, Keimyung University takes charge in the allocation sequence generation, participants enrollment and assigning.
Assignment of interventions: Blinding
Who will be blinded {17a}
Not applicable, this trial is open-label design.
Procedure for unblinding if needed {17b}
Not applicable.
Data collection and management
Plans for assessment and collection of outcomes {18a}
Data will be recorded in the CRF and completed after 6 months after surgery. A study monitoring committee independent from the sponsor and investigator will check the study process and participants’ safety. Any adverse events related to the study will be reported to the study monitoring committee. All data will be stored for 3 years after completion of the study.
Plans to promote participant retention and complete follow-up {18b}
We will offer regular follow-up after the participants are discharged. If the participant cannot come for clinic, a telephone follow-up will be arranged.
Data management {19}
All data for this RCT will be collected after obtaining consent from the participants prior to surgery. All data will be recorded on a paper case report form as well as a digital record form. A participating surgeon or trained researching nurse will perform the postoperative interview to collect the necessary PROMs data.
Confidentiality {27}
All the information collected from this trial will always be protected and all electronic material will be duly stored and backed up in the researcher's computer equipment with a safe password. All the data acquired for this study will be anonymized through the assignment of a trial identification number which will be used only for this study and accessed by only authorized persons.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Not applicable as no biological specimens were collected as part of this trial.
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
All analyses of the primary and secondary endpoints will be conducted with the intention-to-treat population. A per-protocol analysis will also be performed for further comparisons. Normally distributed data will be conducted with Student’s t test. Non-normally distributed data will be examined using the Mann-Whitney U test. The chi-square or Fisher’s exact test will be used to examine categorical variables. Statistical significance will be declared for tests with p values < 0.05.
Interim analyses {21b}
Not Applicable. Interim analyses will not be performed in the present study.
Methods for additional analyses (e.g. subgroup analyses) {20b}
Not Applicable. Additional analyses are not planned in the present study.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Enrolled participants will be excluded if they do not accept randomization or receive intervention after randomization. Participant missing operative information or follow-up data will be excluded.
Plans to give access to the full protocol, participant level-data and statistical code {31c}
We plan to share the data to the public within 6 months after finished the trial.
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
Not Applicable. This trial was approved by the institutional review board at Daegu joint on February 27, 2020 (No: 19-12-001-001) and does not require monitoring by a steering committee.
Composition of the data monitoring committee, its role and reporting structure {21a}
A study monitoring committee independent from the sponsor and investigator will check the study process and participants’ safety. Any adverse events related to the study will be reported to the study monitoring committee.
Adverse event reporting and harms {22}
Any adverse events related to the study will be reported to the study monitoring committee.
Frequency and plans for auditing trial conduct {23}
Not Applicable. Auditing trial conduct is not planned for this study.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
In case of any change to the current protocol, the lead research will be responsible to inform and send the new version the ethical committee for their approval. After the approval the clinical register will be updated and all the amendments will be informed.
Dissemination plans {31a}
The trial results will be published in international medical and scientific journals and presented at national and international conferences.