Clinical trial NCT01679756: INtracorporeal Versus EXTracorpoREal anastoMOsis After Laparoscopic Right Colectomy for Cancer
Official title: INtracorporeal Versus EXTracorpoREal anastoMOsis After Laparoscopic Right Colectomy for Cancer: a Randomized Clinical Trial. (IN EXTREMO Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colorectal Cancer
Keywords: Colorectal cancer
Laparoscopic right hemicolectomy
Intracorporeal anastomosis
Lead sponsor: Ospedale Misericordia e Dolce
Sponsor class: OTHER
First posted: 2012-09-06
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this systematic review is to compare intracorporeal (IA) versus extracorporeal anastomosis (EA) after laparoscopic right hemicolectomy for cancer.

Detailed description: Background. Only a few retrospective publications comparing these anastomotic techniques and no randomized clinical trial has been performed. We conducted a meta-analysis of the existing non randomized comparative studies on the argument: the results suggest that the IA results in better postoperative recovery outcomes, such as shorter hospital stay, faster bowel movement recovery, faster first flatus, faster time to solid diet and lesser analgesic usage.

Design: Two-armed, double-blinded, randomized, controlled study.

The patients will be randomized into two groups:

A. After laparoscopic right colectomy for cancer, anastomosis will be carried out intracorporeally (IA) B. After laparoscopic right colectomy for cancer, anastomosis will be carried out extracorporeally (EA)

Primary endpoint: Surgical morbidity rate defined as any diagnosed morbidity related to surgical technique (anastomotic leakage, anastomotic bleeding, wound infection, ileus) within 60 days from surgery.

Secondary endpoints:

* Intra-operative: operative time, largest incision length (mm), number of nodes harvested, intraoperative complications.
* Early postoperative: mortality, non-surgical site complications.
* Postoperative recovery: bowel movement, first flatus, time to solid diet, nasogastric tube (NGT) reintroduction, day of analgesic usage, length of stay, readmission.

Randomization. The randomization will be obtained through a computer generated program (GraphPad Software, Inc, La Jolla, California, USA). The randomization, will be done before the beginning of the study and it will consist with an ordered series of numbers with a corresponding letter: A for intracorporeal anastomosis and B for extracorporeal anastomosis. This series of numbers will be kept in a central dedicated web database; after right colon cancer diagnosis, if the patient fulfills the inclusion criteria and signs the consent a number, progressive as in order of inclusion, will be assigned to him or her. The letter corresponding to the number, and hence the type of procedure to perform, will be notified to the operating surgeon, who will proceed accordingly.

Blinding. A second surgeon team (different from the one who participate in the intervention), aware of the operative findings but not the management of the anastomosis, will then assume the care of the patient. Postoperative care and ability to be discharged from the hospital will be determined by the second surgical team. This second surgical team will be blinded to the kind of anastomosis. The primary operative team will be in every moment available for emergent consultation.

Power Calculation. The reported prevalence of surgical morbidity after laparoscopic colectomy varies widely from 5-15%16-39, usually depending on the definition of complications and the type of resection performed. The most recent Cochrane review on the argument indicates a 8.6% of local morbidity (Wound infection, anastomotic insufficiency, postoperative ileus, postoperative bleeding)40. Therefore the number of patients required was based on the hope of improving the rate of surgical morbidity from 8.6% to 4.3%; considering a drop-out rate of 5%, 384 patients (192 in the IA group and 192 in the EA group) are necessary to ensure an 80% power with an alpha of 5%, when using a two-sided log-rank test. The statistical power sample calculation was carried out using PASS 2005 (Power Analysis and Sample Size, within the statistical package "NCSS 2004 and PASS 2005").

Sixty-four patients will be included by each of the six centers of the consortium. Only surgeons with at least 30 right colectomies performed with intracorporeal anastomosis will be allowed to recruit patients as first operator.

Statistics. To evaluate significance of differences between the two groups, chi-squared and Fisher's exact test will be used as appropriated for categorical variables, and the non-parametric Mann-Whitney U-test for continuous variables. Significance level will be set at 5%. The statistical analysis will be carried out using the Statistical Package for the Social Sciences (SPSS version 13; SPSS Inc. Chicago, Illinois, USA).

Monitoring. as commonly requested for Randomized Controlled Trials on patients, a strict control of outcomes has been planned during the study. Three experts in laparoscopic colorectal surgery will be designed as member of IN EXTREMO Trial Monitoring Committee. They would have access to the data during the whole course of the study and indicate cessation of the trial if one arm is providing manifestly inferior results.

Eligibility criteria: Inclusion criteria

* Patients suitable for curative surgery 18-80 years old
* ASA grade I-III
* Histhopatological confirmed right only colon carcinoma.
* Elective interventions
* Laparoscopic surgery
* Informed consent

Exclusion criteria

* Informed consent refusal
* Metastatic disease
* Not right colon cancer
* Non elective procedure
* Open or converted operations

Primary outcomes:
measure: Overall surgical morbidity
timeFrame: 60 days from surgery
Secondary outcomes:
measure: Operative time
timeFrame: day of intervention
measure: Largest incision length
timeFrame: day of intervention
measure: Numbers of node harvested
timeFrame: day of intervention
measure: Intraoperative complicatons
timeFrame: day of intervention
measure: Mortality
timeFrame: 60 days from surgery
measure: Non surgical site complications
timeFrame: 60 days from surgery
measure: Bowel movement
timeFrame: 10 days from surgery
measure: First flatus
timeFrame: 10 days from surgery
measure: First stool canalization
timeFrame: 10 days from surgery
measure: Time to solid diet
timeFrame: 10 days from surgery
measure: Naso gastric tube reintroduction
timeFrame: 60 days from surgery
measure: Days of analgesic usage
timeFrame: 60 days from surgery
measure: Length of hospital stay
timeFrame: 60 days from surgery
measure: Readmission
timeFrame: 60 day from intervention
Other outcomes:
Locations:
city: Prato
country: Italy
facility: Misericordia e Dolce Hospital
state: Po
Study officials:
affiliation: Misericordia e Dolce Hospital
name: Marco Scatizzi, MD
role: STUDY_CHAIR
affiliation: Misericordia e Dolce Hospital
name: Francesco Feroci, MD
role: STUDY_DIRECTOR
affiliation: Misericordia e Dolce Hospital
name: Stefano Cantafio, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scatizzi M, Kroning KC, Borrelli A, Andan G, Lenzi E, Feroci F. Extracorporeal versus intracorporeal anastomosis after laparoscopic right colectomy for cancer: a case-control study. World J Surg. 2010 Dec;34(12):2902-8. doi: 10.1007/s00268-010-0743-6.