Rectal CancerReALNCT03941938
ReAL Trial (Rectal Anastomotic seaL)
A study testing Cyanoacrylate reinforcement and No reinforcement in people with Rectal Cancer, run by Societa Italiana di Chirurgia ColoRettale at 1 site in Italy.
Trial summary
The problem of anastomotic leak is particularly relevant in rectal surgery. Many risk factors have been recognized in the onset of this complication. Preventing the anastomotic leak can bring benefits to the patient and the health system. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Cyanoacrylate reinforcement and No reinforcement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteItaly
- Study dates
- 2 May 2019to 2 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Resectable, histologically proven primary adenocarcinoma of the High-medium rectum without internal and/or external sphincter muscle involvement.
- Distal margin of the tumor at least 8 cm form the anal verge
- Staged as follows prior to neoadjuvant chemoradiation: Stage T2 - T4 at MRI
- Patient classified T3-T4 will undergo neoadjuvant chemoradiation if the cancer is located in the extraperitoneal rectum
Who cannot join
- Squamous cell carcinoma
- Adenocarcinoma Stage T1,
- T4 with one of the following: with pelvic side wall involvement, requiring sacrectomy, requiring prostatectomy (partial or total)
- Unresectable primary rectal cancer or Inability to complete R0 resection.
- Rectal cancer under 8 cm from the anal verge requiring colo-anal or ultra low rectal anastomosis
- Recurrent rectal cancer
- Previous pelvic malignancy
- Inability to sign the informed consent
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Dept of Emergency and Organ transplantation - University of Bari
Bari, 70124
Donato F Altomare, Prof, donatofrancesco.altomare@uniba.it
Donato Altomare, MD
About this study
Official title: Prevention of Anastomotic Leak in Colorectal Surgery by Glue Reinforcement. A Prospective Randomized Trial.
The problem of anastomotic leak is particularly relevant in rectal surgery. Many risk factors have been recognized in the onset of this complication. Preventing the anastomotic leak can bring benefits to the patient and the health system.
Several attempts have been proposed to reduce the risk of anastomotic leakage in rectal cancer surgery including suture protection with omental flap and external suture reinforcement by biological glue or mesh.
Read more
Cyanoacrylate (Glubran 2®) is a synthetic glue with sealing, adhesive and hemostatic properties widely used in surgery. The sealing effect creates an antiseptic barrier against bacteria.
The hypothesis is that the application of nebulized cyanoacrylate to the colo-rectal anastomosis in open or laparoscopic/robotic rectal surgery can prevent the leakage
Read the detailed description
Colorectal cancer (CRC) is the second most common cause of cancer-related death in male and the third in females in Western Countries accounting for more than 500,000 deaths in 2013 worldwide.
One of the most worrying postoperative complication in colorectal surgery is the anastomotic leak which can occur in about 10-15% of the cases.
This complication severely impact clinical outcomes with increased risk of death or permanent stoma, higher risk of local recurrence) and relevant increase in hospital costs (length of hospital stay, admission to intensive care, re-interventions).
The problem of anastomotic leak is particularly relevant in rectal surgery. The more distal the anastomosis, the higher the likelihood of failure, with resection of a distal rectal cancer having almost a five-fold increased risk of anastomotic leak compared with resection for colon cancer.
In fact, anastomotic Leakage (AL) is the most severe complication after Low anterior resection of rectum for cancer, occurring between 3 and 24 % of patients.
Many risk factors have been recognized in the onset of this complication, including gender (male patient have a higher anastomotic leak rate), malnutrition, obesity an diabet, american society anesthesiologists (ASA) score, tobacco use, cardiovascular disease, immunosuppression, use of NSAID, preoperative pelvis radiation.
Other intraoperative risk factors considered are the splenic flexure mobilization with proximal ligation of the inferior mesenteric artery (IMA), positive intraoperative Air-Leak Test and the perfusion of the anastomosis.
Temporary fecal diversion has also been suggested (although a diverting stoma mitigates the clinical consequences of an anastomotic leak but does not prevent it.
Other intraoperative technical factors include the use of single or double stapled anastomotic techniques, with or without transanal reinforcing sutures.
Therefore, preventing the anastomotic leak can bring benefits to the patient and the health system.
All the risk factors described above represent the rationale that justifies the use of intraoperative procedures to prevent the anastomotic leak, such as additional manual stiches to the mechanical suture and / or patches of collagen (proper reinforcement or buttressing) or of sealants.
Several attempts have been proposed to reduce the risk of AL in rectal cancer surgery including suture protection with omental flap and external suture reinforcement by biological glue or mesh.
Some Authors have reported good results of reinforcement of the colon anastomosis with cyanoacrylate glue. in a porcine model.
Cyanoacrylate is a synthetic glue with sealing, adhesive and haemostatic properties widely used in surgery. Furthermore the sealing effect creates an antiseptic barrier against bacteria.
Several clinical studies have described the utility of cyanoacrylate glue mainly in vascular surgery, urology and bariatric surgery.
Considering its mechanical, physical, biological properties and its safety, cyanoacrylate glue could facilitate the healing of the colorectal anastomosis reducing leak rate, without negative effects on perfusion.
The hypothesis is that the application of nebulized cyanoacrylate to the colo-rectal anastomosis in open or laparoscopic/robotic rectal surgery can prevent the leakage
- Conditions
- Rectal Cancer
- Being tested
- Cyanoacrylate reinforcement, No reinforcement
- Keywords
- colorectal anastomosis, leakage
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyanoacrylate reinforcementProcedure or surgery
Anastomosis Reinforcement with with nebulization of 1cc of glue on the anastomosis line
No reinforcementProcedure or surgery
Nothing applied on the anastomosis line
| Study group | Role | What they receive |
|---|---|---|
| Cyanoacrylate | Experimental | the anastomotic reinforcement with nebulized cyanoacrylate glue using the special short catheter device for open surgery or the laparoscopic catheter. Receives: Procedure: Cyanoacrylate reinforcement |
| No reinforcement | Active comparator | No reinforcement will be applied on the anastomosis line Receives: Procedure: No reinforcement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anastomotic leak
leakage of the colorectal anastomosis clinically proven or with two sides X-ray
Measured: 30 days
Secondary outcomes (4)
length of hospital stay
duration of hospital stay
Measured: 30 days
Blood loss
the amount of bleeding during the operation
Measured: 1 day
Surgical site infection
purulent discharge from the wound with positive culture
Measured: 30 days
Postoperative complications
complications after the operation
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2019
- Study start2 May 2019
- Primary completion2 Dec 2020 (estimated)
- Study completion2 Jul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Societa Italiana di Chirurgia ColoRettale
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Donato Altomare, Prof, Principal investigator, Societa Italiana di Chirurgia ColoRettaleArcangelo Picciariello, MD, Principal investigator, Societa Italiana di Chirurgia ColoRettale
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03941938
- Sponsor's protocol ID
- 131/2019
- Acronym
- ReAL
- Status last verified
- May 2020
- First submitted
- 6 May 2019
- Last updated
- 20 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Thomas MS, Margolin DA. Management of Colorectal Anastomotic Leak. Clin Colon Rectal Surg. 2016 Jun;29(2):138-44. doi: 10.1055/s-0036-1580630.
PubMed 27247539de la Portilla F, Zbar AP, Rada R, Vega J, Cisneros N, Maldonado VH, Utrera A, Espinosa E. Bioabsorbable staple-line reinforcement to reduce staple-line bleeding in the transection of mesenteric vessels during laparoscopic colorectal resection: a pilot study. Tech Coloproctol. 2006 Dec;10(4):335-8. doi: 10.1007/s10151-006-0303-0. Epub 2006 Nov 27.
PubMed 17115313Wiggins T, Markar SR, Arya S, Hanna GB. Anastomotic reinforcement with omentoplasty following gastrointestinal anastomosis: A systematic review and meta-analysis. Surg Oncol. 2015 Sep;24(3):181-6. doi: 10.1016/j.suronc.2015.06.011. Epub 2015 Jun 17.
PubMed 26116395Boersema GSA, Vennix S, Wu Z, Te Lintel Hekkert M, Duncker DGM, Lam KH, Menon AG, Kleinrensink GJ, Lange JF. Reinforcement of the colon anastomosis with cyanoacrylate glue: a porcine model. J Surg Res. 2017 Sep;217:84-91. doi: 10.1016/j.jss.2017.05.001. Epub 2017 May 10.
PubMed 28595813Montanaro L, Arciola CR, Cenni E, Ciapetti G, Savioli F, Filippini F, Barsanti LA. Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use. Biomaterials. 2001 Jan;22(1):59-66. doi: 10.1016/s0142-9612(00)00163-0.
PubMed 11085384Wu Z, Boersema GS, Vakalopoulos KA, Daams F, Sparreboom CL, Kleinrensink GJ, Jeekel J, Lange JF. Critical analysis of cyanoacrylate in intestinal and colorectal anastomosis. J Biomed Mater Res B Appl Biomater. 2014 Apr;102(3):635-42. doi: 10.1002/jbm.b.33039. Epub 2013 Oct 24.
PubMed 24155114Tomasicchio G, Martines G, Tartaglia N, Buonfantino M, Restini E, Carlucci B, Giove C, Dezi A, Ranieri C, Logrieco G, Vincenti L, Ambrosi A, Altomare DF, De Fazio M, Picciariello A. Suture reinforcement using a modified cyanoacrylate glue to prevent anastomotic leak in colorectal surgery: a prospective multicentre randomized trial : The Rectal Anastomotic seaL (ReAL) trial. Tech Coloproctol. 2024 Aug 5;28(1):95. doi: 10.1007/s10151-024-02967-7.
PubMed 39103661
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Anastomotic Leak in Colorectal Surgery by Glue Reinforcement. A Prospective Randomized Trial.
- ClinicalTrials.gov ID
- NCT03941938
- Acronym / sponsor ID
- ReAL / 131/2019
- Conditions
- Rectal Cancer
- Keywords
- colorectal anastomosis, leakage
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Societa Italiana di Chirurgia ColoRettaleResearch network
- Study start
- 2 May 2019 (actual)
- Primary completion
- 2 Dec 2020 (estimated)
- Study completion
- 2 Jul 2021 (estimated)
- First posted
- 8 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The problem of anastomotic leak is particularly relevant in rectal surgery. Many risk factors have been recognized in the onset of this complication. Preventing the anastomotic leak can bring benefits to the patient and the health system.
Several attempts have been proposed to reduce the risk of anastomotic leakage in rectal cancer surgery including suture protection with omental flap and external suture reinforcement by biological glue or mesh.
Cyanoacrylate (Glubran 2®) is a synthetic glue with sealing, adhesive and hemostatic properties widely used in surgery. The sealing effect creates an antiseptic barrier against bacteria.
The hypothesis is that the application of nebulized cyanoacrylate to the colo-rectal anastomosis in open or laparoscopic/robotic rectal surgery can prevent the leakage
Detailed description
Colorectal cancer (CRC) is the second most common cause of cancer-related death in male and the third in females in Western Countries accounting for more than 500,000 deaths in 2013 worldwide.
One of the most worrying postoperative complication in colorectal surgery is the anastomotic leak which can occur in about 10-15% of the cases.
This complication severely impact clinical outcomes with increased risk of death or permanent stoma, higher risk of local recurrence) and relevant increase in hospital costs (length of hospital stay, admission to intensive care, re-interventions).
The problem of anastomotic leak is particularly relevant in rectal surgery. The more distal the anastomosis, the higher the likelihood of failure, with resection of a distal rectal cancer having almost a five-fold increased risk of anastomotic leak compared with resection for colon cancer.
In fact, anastomotic Leakage (AL) is the most severe complication after Low anterior resection of rectum for cancer, occurring between 3 and 24 % of patients.
Many risk factors have been recognized in the onset of this complication, including gender (male patient have a higher anastomotic leak rate), malnutrition, obesity an diabet, american society anesthesiologists (ASA) score, tobacco use, cardiovascular disease, immunosuppression, use of NSAID, preoperative pelvis radiation.
Other intraoperative risk factors considered are the splenic flexure mobilization with proximal ligation of the inferior mesenteric artery (IMA), positive intraoperative Air-Leak Test and the perfusion of the anastomosis.
Temporary fecal diversion has also been suggested (although a diverting stoma mitigates the clinical consequences of an anastomotic leak but does not prevent it.
Other intraoperative technical factors include the use of single or double stapled anastomotic techniques, with or without transanal reinforcing sutures.
Therefore, preventing the anastomotic leak can bring benefits to the patient and the health system.
All the risk factors described above represent the rationale that justifies the use of intraoperative procedures to prevent the anastomotic leak, such as additional manual stiches to the mechanical suture and / or patches of collagen (proper reinforcement or buttressing) or of sealants.
Several attempts have been proposed to reduce the risk of AL in rectal cancer surgery including suture protection with omental flap and external suture reinforcement by biological glue or mesh.
Some Authors have reported good results of reinforcement of the colon anastomosis with cyanoacrylate glue. in a porcine model.
Cyanoacrylate is a synthetic glue with sealing, adhesive and haemostatic properties widely used in surgery. Furthermore the sealing effect creates an antiseptic barrier against bacteria.
Several clinical studies have described the utility of cyanoacrylate glue mainly in vascular surgery, urology and bariatric surgery.
Considering its mechanical, physical, biological properties and its safety, cyanoacrylate glue could facilitate the healing of the colorectal anastomosis reducing leak rate, without negative effects on perfusion.
The hypothesis is that the application of nebulized cyanoacrylate to the colo-rectal anastomosis in open or laparoscopic/robotic rectal surgery can prevent the leakage
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyanoacrylate | Experimental | Procedure: Cyanoacrylate reinforcementthe anastomotic reinforcement with nebulized cyanoacrylate glue using the special short catheter device for open surgery or the laparoscopic catheter. |
| No reinforcement | Active comparator | Procedure: No reinforcementNo reinforcement will be applied on the anastomosis line |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Resectable, histologically proven primary adenocarcinoma of the High-medium rectum without internal and/or external sphincter muscle involvement.
- Distal margin of the tumor at least 8 cm form the anal verge
- Staged as follows prior to neoadjuvant chemoradiation: Stage T2 - T4 at MRI
- Patient classified T3-T4 will undergo neoadjuvant chemoradiation if the cancer is located in the extraperitoneal rectum
Key exclusion criteria (8 listed)
- Squamous cell carcinoma
- Adenocarcinoma Stage T1,
- T4 with one of the following: with pelvic side wall involvement, requiring sacrectomy, requiring prostatectomy (partial or total)
- Unresectable primary rectal cancer or Inability to complete R0 resection.
- Rectal cancer under 8 cm from the anal verge requiring colo-anal or ultra low rectal anastomosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyanoacrylate reinforcementAnastomosis Reinforcement with with nebulization of 1cc of glue on the anastomosis line | Procedure or surgery | Cyanoacrylate |
| No reinforcementNothing applied on the anastomosis line | Procedure or surgery | No reinforcement |
Primary outcome
Anastomotic leak
Time frame: 30 days
leakage of the colorectal anastomosis clinically proven or with two sides X-ray
4 secondary outcomes
length of hospital stay
Time frame: 30 days
Blood loss
Time frame: 1 day
Surgical site infection
Time frame: 30 days
Postoperative complications
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2020.
- Results publication: PubMed 27247539Thomas MS, Margolin DA. Management of Colorectal Anastomotic Leak. Clin Colon Rectal Surg. 2016 Jun;29(2):138-44. doi: 10.1055/s-0036-1580630.
- Results publication: PubMed 17115313de la Portilla F, Zbar AP, Rada R, Vega J, Cisneros N, Maldonado VH, Utrera A, Espinosa E. Bioabsorbable staple-line reinforcement to reduce staple-line bleeding in the transection of mesenteric vessels during laparoscopic colorectal resection: a pilot study. Tech Coloproctol. 2006 Dec;10(4):335-8. doi: 10.1007/s10151-006-0303-0. Epub 2006 Nov 27.
- Results publication: PubMed 26116395Wiggins T, Markar SR, Arya S, Hanna GB. Anastomotic reinforcement with omentoplasty following gastrointestinal anastomosis: A systematic review and meta-analysis. Surg Oncol. 2015 Sep;24(3):181-6. doi: 10.1016/j.suronc.2015.06.011. Epub 2015 Jun 17.
- Results publication: PubMed 28595813Boersema GSA, Vennix S, Wu Z, Te Lintel Hekkert M, Duncker DGM, Lam KH, Menon AG, Kleinrensink GJ, Lange JF. Reinforcement of the colon anastomosis with cyanoacrylate glue: a porcine model. J Surg Res. 2017 Sep;217:84-91. doi: 10.1016/j.jss.2017.05.001. Epub 2017 May 10.
- Results publication: PubMed 11085384Montanaro L, Arciola CR, Cenni E, Ciapetti G, Savioli F, Filippini F, Barsanti LA. Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use. Biomaterials. 2001 Jan;22(1):59-66. doi: 10.1016/s0142-9612(00)00163-0.
- Results publication: PubMed 24155114Wu Z, Boersema GS, Vakalopoulos KA, Daams F, Sparreboom CL, Kleinrensink GJ, Jeekel J, Lange JF. Critical analysis of cyanoacrylate in intestinal and colorectal anastomosis. J Biomed Mater Res B Appl Biomater. 2014 Apr;102(3):635-42. doi: 10.1002/jbm.b.33039. Epub 2013 Oct 24.
- Derived from this study: PubMed 39103661Tomasicchio G, Martines G, Tartaglia N, Buonfantino M, Restini E, Carlucci B, Giove C, Dezi A, Ranieri C, Logrieco G, Vincenti L, Ambrosi A, Altomare DF, De Fazio M, Picciariello A. Suture reinforcement using a modified cyanoacrylate glue to prevent anastomotic leak in colorectal surgery: a prospective multicentre randomized trial : The Rectal Anastomotic seaL (ReAL) trial. Tech Coloproctol. 2024 Aug 5;28(1):95. doi: 10.1007/s10151-024-02967-7.
Related trials for Rectal Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
Not yet recruitingPhase 2
Exploratory Study of Short-Course Radiotherapy Followed by Adebrelimab Combined With Chemotherapy for Organ Preservation in Locally Advanced Rectal Cancer
Locally Advanced Resectable Rectal Cancer
RecruitingObservational study
ABCSG R07 Rectal Cancer Registry
Rectal Cancer, Adenocarcinoma of Rectum
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donato Altomare, Prof principal investigator
Societa Italiana di Chirurgia ColoRettale
Arcangelo Picciariello, MD principal investigator
Societa Italiana di Chirurgia ColoRettale
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cyanoacrylate reinforcement and No reinforcement in people with Rectal Cancer, run by Societa Italiana di Chirurgia ColoRettale at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Donato Altomare, MD (+39 3397593066, donatofrancesco.altomare@uniba.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anastomotic leak (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03941938, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2020.