Clinical Trial for the Optimization of Indocyanine Green Administration in NIRF-C During L.Cholecystectomy.

Laparoscopic Cholecystectomy Clinical Trial

— DOTIG  

Official title:

Randomized Clinical Trial for the Optimization of Indocyanine Green Administration in Near-infrared Fluorescent Cholangiography During Laparoscopic Cholecystectomy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05419947
• Other study ID #: IBS-DOTIG-ECM-2202
• Secondary ID: 2022-000904-36
• Status: Completed
• Phase: Phase 4
• Start date: June 20, 2022
• Est. completion date: October 24, 2023

Study information

• Verified date: November 2023
• Source: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Laparoscopic cholecystectomy is one of the most performed surgical procedures worldwide. One of its most serious complications is injury to the main bile duct, with an incidence of less than 1%. There are different surgical strategies that try to reduce this complication, with indocyanine green fluorescence cholangiography being one of the most recent to appear. This technique is becoming a great tool during laparoscopic cholecystectomy. Despite the great rise of the procedure, today there is a great disparity in the administration protocols of indocyanine green during the procedure. Goals. The main objective of the study is to analyze whether there are differences between different types of doses and administration intervals of indocyanine green to obtain quality fluorescent cholangiography during laparoscopic cholecystectomy. In addition, the factors that influence the results of the technique will be sought.

Description:

Symptomatic cholelithiasis is a pathology of great relevance in the world population, with prevalence rates of up to 20%. The standard treatment for cholelithiasis is laparoscopic cholecystectomy (LC). One of the most serious complications of LC is injury to the main bile duct (LVB). Although this complication has incidences of less than 1% (0.3-0.7% in the different series), the consequences it causes are highly relevant. LVB is related to a significant increase in patient morbidity and mortality, a significant deterioration in quality of life, a very significant increase in healthcare costs and not insignificant medical-legal consequences. Indocyanine green fluorescence cholangiography (CF-VI) is a novel technique that allows precise and real-time anatomical visualization of the extrahepatic biliary anatomy, facilitating surgery and reducing the risk of complications. Currently, there are large differences in LV administration protocols during CF in LC. The precise dose and the ideal moment of administration are key to achieving adequate visualization of the critical vascular and biliary structures and to reduce the fluorescence emitted by the hepatic parenchyma, which could hinder correct anatomical visualization. In relation to the dose, there are many protocols for IV administration, by means of a single dose or a dose adjusted for the patient's body weight. Some authors advocate the administration of IV 24 hours before the procedure, in order to avoid hepatic fluorescence. However, in the context of major outpatient surgery, outpatient surgery or short-stay surgery, we believe that this practice is not currently logistically feasible. Other groups administer the IV with a variable range of time interval. The recent preliminary results of the European Registry of Fluorescent Image Guided Surgery show the great disparity of preoperative LV administration protocols. Therefore, it is necessary to protocolize the administration of the drug based on the results of randomized clinical trials.. The precise dose and the ideal moment of administration are key to achieving adequate visualization of the critical vascular and biliary structures and to reduce the fluorescence emitted by the hepatic parenchyma, which could hinder correct anatomical visualization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 24, 2023
• Est. primary completion date: May 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age over 18 years.
• Autonomy, self-sufficiency and independence.
• Scheduled CL indication:
• Symptomatic cholelithiasis: history of biliary colic, acute lithiasic cholecystitis, choledocholithiasis, acute ascending cholangitis of lithiasic origin or acute lithiasic pancreatitis.
• Gallbladder polyps with indication for laparoscopic surgery.
• Vesicular adenomyomatosis with indication for laparoscopic surgery.
• Indication of early LC (<72 hours of admission for acute stone cholecystitis/acute acalculous cholecystitis/complicated biliary colic).
• Deferred urgency LC indication.
• Understanding of information.
• Signature of the informed consent.

Exclusion Criteria:

• Age less than 18 years.
• Disability.
• Pregnancy or lactation.
• Chronic kidney disease (Stage > IIIb).
• Previous adverse reactions or allergies to VI.
• Previous adverse reactions or allergies to VI excipients.
• Adverse reactions or confirmed allergies to iodinated contrast agents.
• Functional thyroid pathology (hyperthyroidism, thyroiditis, toxic multinodular goiter, functioning thyroid adenoma).
• Urgent non-deferrable/emergent gallbladder surgery.
• Initial surgery by laparotomy.
• Previous suspicion of gallbladder carcinoma.
• Inability to understand the information needed to participate in the study.
• Rejection of inclusion within the study protocol.

Related Conditions & MeSH terms

• Laparoscopic Cholecystectomy

Intervention

Drug:
• VERDYE powder for solution for injection 25 mg
Verdye 25 mg contains sodium VI powder for solution for injection. VI is a water-soluble agent with a spectral absorption peak of 800 nm. It is a drug approved for diagnostic use only and is indicated for the measurement of the excretory function of the liver.

Locations

Country	Name	City	State
Spain	Hospital Universitario Germans Trias i Pujol.	Badalona	Barcelona
Spain	Complejo Asistencial Universitario de Salamanca	Salamanca

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León	Instituto de Investigación Biomédica de Salamanca

Country where clinical trial is conducted

Spain, 

References & Publications (19)

Agnus V, Pesce A, Boni L, Van Den Bos J, Morales-Conde S, Paganini AM, Quaresima S, Balla A, La Greca G, Plaudis H, Moretto G, Castagnola M, Santi C, Casali L, Tartamella L, Saadi A, Picchetto A, Arezzo A, Marescaux J, Diana M. Fluorescence-based cholangiography: preliminary results from the IHU-IRCAD-EAES EURO-FIGS registry. Surg Endosc. 2020 Sep;34(9):3888-3896. doi: 10.1007/s00464-019-07157-3. Epub 2019 Oct 7. — View Citation

Ansaloni L, Pisano M, Coccolini F, Peitzmann AB, Fingerhut A, Catena F, Agresta F, Allegri A, Bailey I, Balogh ZJ, Bendinelli C, Biffl W, Bonavina L, Borzellino G, Brunetti F, Burlew CC, Camapanelli G, Campanile FC, Ceresoli M, Chiara O, Civil I, Coimbra R, De Moya M, Di Saverio S, Fraga GP, Gupta S, Kashuk J, Kelly MD, Koka V, Jeekel H, Latifi R, Leppaniemi A, Maier RV, Marzi I, Moore F, Piazzalunga D, Sakakushev B, Sartelli M, Scalea T, Stahel PF, Taviloglu K, Tugnoli G, Uraneus S, Velmahos GC, Wani I, Weber DG, Viale P, Sugrue M, Ivatury R, Kluger Y, Gurusamy KS, Moore EE. 2016 WSES guidelines on acute calculous cholecystitis. World J Emerg Surg. 2016 Jun 14;11:25. doi: 10.1186/s13017-016-0082-5. eCollection 2016. Erratum In: World J Emerg Surg. 2016 Nov 4;11:52. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae. — View Citation

Dip F, LoMenzo E, Sarotto L, Phillips E, Todeschini H, Nahmod M, Alle L, Schneider S, Kaja L, Boni L, Ferraina P, Carus T, Kokudo N, Ishizawa T, Walsh M, Simpfendorfer C, Mayank R, White K, Rosenthal RJ. Randomized Trial of Near-infrared Incisionless Fluorescent Cholangiography. Ann Surg. 2019 Dec;270(6):992-999. doi: 10.1097/SLA.0000000000003178. — View Citation

Flum DR, Dellinger EP, Cheadle A, Chan L, Koepsell T. Intraoperative cholangiography and risk of common bile duct injury during cholecystectomy. JAMA. 2003 Apr 2;289(13):1639-44. doi: 10.1001/jama.289.13.1639. — View Citation

Gupta V, Jain G. Safe laparoscopic cholecystectomy: Adoption of universal culture of safety in cholecystectomy. World J Gastrointest Surg. 2019 Feb 27;11(2):62-84. doi: 10.4240/wjgs.v11.i2.62. — View Citation

Ishizawa T, Bandai Y, Ijichi M, Kaneko J, Hasegawa K, Kokudo N. Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy. Br J Surg. 2010 Sep;97(9):1369-77. doi: 10.1002/bjs.7125. — View Citation

Lim SH, Tan HTA, Shelat VG. Comparison of indocyanine green dye fluorescent cholangiography with intra-operative cholangiography in laparoscopic cholecystectomy: a meta-analysis. Surg Endosc. 2021 Apr;35(4):1511-1520. doi: 10.1007/s00464-020-08164-5. Epub 2021 Jan 4. — View Citation

Mascagni P, Vardazaryan A, Alapatt D, Urade T, Emre T, Fiorillo C, Pessaux P, Mutter D, Marescaux J, Costamagna G, Dallemagne B, Padoy N. Artificial Intelligence for Surgical Safety: Automatic Assessment of the Critical View of Safety in Laparoscopic Cholecystectomy Using Deep Learning. Ann Surg. 2022 May 1;275(5):955-961. doi: 10.1097/SLA.0000000000004351. Epub 2020 Nov 16. — View Citation

Nuzzo G, Giuliante F, Giovannini I, Ardito F, D'Acapito F, Vellone M, Murazio M, Capelli G. Bile duct injury during laparoscopic cholecystectomy: results of an Italian national survey on 56 591 cholecystectomies. Arch Surg. 2005 Oct;140(10):986-92. doi: 10.1001/archsurg.140.10.986. — View Citation

Pesce A, Piccolo G, Lecchi F, Fabbri N, Diana M, Feo CV. Fluorescent cholangiography: An up-to-date overview twelve years after the first clinical application. World J Gastroenterol. 2021 Sep 28;27(36):5989-6003. doi: 10.3748/wjg.v27.i36.5989. — View Citation

Reinhart MB, Huntington CR, Blair LJ, Heniford BT, Augenstein VA. Indocyanine Green: Historical Context, Current Applications, and Future Considerations. Surg Innov. 2016 Apr;23(2):166-75. doi: 10.1177/1553350615604053. Epub 2015 Sep 10. — View Citation

Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg. 1995 Jan;180(1):101-25. No abstract available. — View Citation

Tazuma S, Unno M, Igarashi Y, Inui K, Uchiyama K, Kai M, Tsuyuguchi T, Maguchi H, Mori T, Yamaguchi K, Ryozawa S, Nimura Y, Fujita N, Kubota K, Shoda J, Tabata M, Mine T, Sugano K, Watanabe M, Shimosegawa T. Evidence-based clinical practice guidelines for cholelithiasis 2016. J Gastroenterol. 2017 Mar;52(3):276-300. doi: 10.1007/s00535-016-1289-7. Epub 2016 Dec 10. — View Citation

van den Bos J, Wieringa FP, Bouvy ND, Stassen LPS. Optimizing the image of fluorescence cholangiography using ICG: a systematic review and ex vivo experiments. Surg Endosc. 2018 Dec;32(12):4820-4832. doi: 10.1007/s00464-018-6233-x. Epub 2018 May 18. — View Citation

Verbeek FP, Schaafsma BE, Tummers QR, van der Vorst JR, van der Made WJ, Baeten CI, Bonsing BA, Frangioni JV, van de Velde CJ, Vahrmeijer AL, Swijnenburg RJ. Optimization of near-infrared fluorescence cholangiography for open and laparoscopic surgery. Surg Endosc. 2014 Apr;28(4):1076-82. doi: 10.1007/s00464-013-3305-9. — View Citation

Vlek SL, van Dam DA, Rubinstein SM, de Lange-de Klerk ESM, Schoonmade LJ, Tuynman JB, Meijerink WJHJ, Ankersmit M. Biliary tract visualization using near-infrared imaging with indocyanine green during laparoscopic cholecystectomy: results of a systematic review. Surg Endosc. 2017 Jul;31(7):2731-2742. doi: 10.1007/s00464-016-5318-7. Epub 2016 Nov 14. — View Citation

Widjaja SP, Fischer H, Brunner AR, Honigmann P, Metzger J. Acceptance of Ambulatory Laparoscopic Cholecystectomy in Central Switzerland. World J Surg. 2017 Nov;41(11):2731-2734. doi: 10.1007/s00268-017-4098-0. — View Citation

Yokoe M, Hata J, Takada T, Strasberg SM, Asbun HJ, Wakabayashi G, Kozaka K, Endo I, Deziel DJ, Miura F, Okamoto K, Hwang TL, Huang WS, Ker CG, Chen MF, Han HS, Yoon YS, Choi IS, Yoon DS, Noguchi Y, Shikata S, Ukai T, Higuchi R, Gabata T, Mori Y, Iwashita Y, Hibi T, Jagannath P, Jonas E, Liau KH, Dervenis C, Gouma DJ, Cherqui D, Belli G, Garden OJ, Gimenez ME, de Santibanes E, Suzuki K, Umezawa A, Supe AN, Pitt HA, Singh H, Chan ACW, Lau WY, Teoh AYB, Honda G, Sugioka A, Asai K, Gomi H, Itoi T, Kiriyama S, Yoshida M, Mayumi T, Matsumura N, Tokumura H, Kitano S, Hirata K, Inui K, Sumiyama Y, Yamamoto M. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):41-54. doi: 10.1002/jhbp.515. Epub 2018 Jan 9. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of biliary structures prior to dissection of the hepatocystic triangle.	Identification of biliary structures prior to dissection of the hepatocystic triangle.; "yes" or "no" will be used to determine whether to display: Identification of the cystic duct prior to dissection; Identification of the common bile duct prior to dissection; Identification of the junction of the cystic duct with the common bile duct prior to dissection; Identification of the union of the cystic duct with the gallbladder prior to dissection; Identification of the common hepatic duct prior to dissection; Identification of biliary anatomical variables prior to dissection 6.1. High implantation cystic duct 6.2. short cystic duct 6.3. Anterior spiral cystic duct, with mouth on the left side of the bile duct 6.4. Posterior spiral cystic duct, with mouth on the left side of the bile duct 6.5. Aberrant right hepatic duct, with drainage into the cystic duct 6.6. Others	At the time of the surgical procedure
Primary	Identification of biliary structures after dissection of the hepatocystic triangle.	Identification of biliary structures after dissection of the hepatocystic triangle.; "yes" or "no" will be used to determine whether to display: Identification of the cystic duct prior to dissection; Identification of the common bile duct prior to dissection; Identification of the junction of the cystic duct with the common bile duct prior to dissection; Identification of the union of the cystic duct with the gallbladder prior to dissection; Identification of the common hepatic duct prior to dissection; Identification of biliary anatomical variables prior to dissection 6.1. High implantation cystic duct 6.2. short cystic duct 6.3. Anterior spiral cystic duct, with mouth on the left side of the bile duct 6.4. Posterior spiral cystic duct, with mouth on the left side of the bile duct 6.5. Aberrant right hepatic duct, with drainage into the cystic duct 6.6. Others	At the time of the surgical procedure
Secondary	Degree of identification of biliary structures prior to dissection of the hepatocystic triangle.	Degree of identification of biliary structures prior to dissection of the hepatocystic triangle.; The following scale will be used: 1=little, 2=sufficient, 3=quite a bit, 4=good, 5=excellent	At the time of the surgical procedure
Secondary	Degree of identification of biliary structures after dissection of the hepatocystic triangle.	Degree of identification of biliary structures after dissection of the hepatocystic triangle.; The following scale will be used: 1=little, 2=sufficient, 3=quite a bit, 4=good, 5=excellent	At the time of the surgical procedure
Secondary	Extent to which fluorescence cholangiography was perceived as useful for surgery	Extent to which fluorescence cholangiography was perceived as useful for surgery The following scale will be used: 0=not useful, 1=moderately useful, 2=very useful	At the time of the surgical procedure
Secondary	Extent to which liver fundus fluorescence (contrast between liver and ducts) was perceived as disturbing.	Extent to which liver fundus fluorescence (contrast between liver and ducts) was perceived as disturbing.; The following scale will be used: 0=no disturbance, 1=slightly disturbed, 2=disturbed visualization, but cystic-bile duct junction was clearly visible before dissection, 3=disturbed visualization and cystic-bile duct junction was only visible after dissection. dissection and 4= very disturbed: it was impossible to correctly visualize the biliary structures	At the time of the surgical procedure