Anastomotic LeakEDOBSNCT03587532
Assessment of Graft Perfusion and Oxygenation for Improved Outcome in Esophageal Cancer Surgery
A study testing Indocyanine green angiography, Hemodynamic evaluation and Biological and pathological markers of ischemia in people with Anastomotic Leak and Esophageal Cancer, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
After the esophagectomy, the stomach is most commonly used to restore continuity of the upper gastro-intestinal tract. The esophagogastric anastomosis is prone to serious complications such as anastomotic leakage (AL) The reported incidence of AL after esophagectomy ranges from 5%-20%. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Anastomotic Leak, Esophageal Cancer
- What is being tested?
- Indocyanine green angiography, Hemodynamic evaluation and Biological and pathological markers of ischemia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteBelgium
- Study dates
- 13 Dec 2021to 31 Dec 2024
- 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
- Pre- and intraoperatively
- Subjects ≥ 18 years and ≤ 75 years who are willing to participate and provide written informed consent prior to any study-related procedures.
- Subjects scheduled for elective minimally invasive Ivor Lewis esophagectomy
- Intrathoracic circular stapled esophago-gastric anastomosis
Who cannot join
- Preoperatively
- Known hypersensitivity to ICG
- Female patients who are pregnant or nursing
- Participation in other studies involving investigational drugs or devices.
- Use of Avastin™ (bevacizumab) or other anti vascular endothelial growth factor (VEGF) agents within 30 days prior to surgery
- Intra-operatively
Show all 9Show fewer
- Intra-operative findings that may preclude conduct of the study procedures
- Anastomosis performed differently than the standard of care
- Excessive bleeding (>500 ml) prior to anastomosis
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
University Hospital
Ghent, 9000
Elke Van Daele, MD, +32 9 332 08 29, elke.vandaele@uzgent.be
About this study
After the esophagectomy, the stomach is most commonly used to restore continuity of the upper gastro-intestinal tract. The esophagogastric anastomosis is prone to serious complications such as anastomotic leakage (AL) The reported incidence of AL after esophagectomy ranges from 5%-20%. The AL associated mortality ranges from 18-40% compared with an overall in-hospital mortality of 4-6%. The main cause of AL is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft. Clinical judgment is unreliable in determining anastomotic perfusion. Therefore, an objective, validated, and reproducible method to evaluate tissue perfusion at the anastomotic site is urgently needed. Indocyanine green angiography (ICGA) is a near infrared fluorescent (NIRF) perfusion imaging using indocyanine green (ICG). ICGA is a safe, easy and reproducible method for graft perfusion analysis, but it is not yet calibrated. The purpose of this study is to evaluate the feasibility of quantification of ICGA to assess graft perfusion and its influence on AL in patients after minimally invasive Ivor Lewis esophagectomy (MIE) for cancer.
Read the detailed description
Background: The incidence of adenocarcinoma of the esophagus is rapidly increasing, resulting in 480 000 newly diagnosed patients annually in the world1. Surgery remains the cornerstone of therapy for curable esophageal cancer (EC) patients. After the esophagectomy, the stomach is most commonly used to restore continuity of the upper gastro-intestinal tract. The esophagogastric anastomosis is prone to serious complications such as anastomotic leakage (AL), fistula, bleeding, and stricture. The reported incidence of AL after esophagectomy ranges from 5%-20% 2-6. The AL associated mortality ranges from 18-40% compared with an overall in-hospital mortality of 4-6% 2, 7, 8. The main cause of AL is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft. Clinical judgment is unreliable in determining anastomotic perfusion. Therefore, an objective, validated, and reproducible method to evaluate tissue perfusion at the anastomotic site is urgently needed. Near infrared fluorescent (NIRF) perfusion imaging using indocyanine green (ICG) is an emerging modality based on excitation and resulting fluorescence in the near-infrared range (λ = 700-900 nm).
Aims:
- To perform intraoperative ICG based NIRF angiography of the stomach graft during minimally invasive esophagectomy in EC patients, and to calculate tissue blood flow and volume using curve analysis and advanced compartmental modeling;
- To validate imaging based perfusion parameters by comparison with hemodynamic parameters, blood and tissue expression of hypoxia induced markers, and tissue mitochondrial respiration rate
- To evaluate the ability of NIRF based perfusion measurement to predict anastomotic leakage.
Methods: Patients (N=70) with resectable EC will be recruited to undergo minimally invasive Ivor Lewis esophagectomy according to the current standard of care. ICG based angiography will be performed after creation of the stomach graft and after thoracic pull-up of the graft. Dynamic digital images will be obtained starting immediately after intravenous bolus administration of 0.5 mg/kg of ICG. The resulting images will be subjected to curve analysis (time to peak, washout time) and to compartmental analysis based on the AATH kinetic model (adiabatic approximation to tissue homogeneity, which allows to calculate blood flow, blood volume, vascular heterogeneity, and vascular leakage). The calculated perfusion parameters will be compared to intraoperative hemodynamic data (PiCCO catheter) to evaluate how patient hemodynamics affect graft perfusion. To verify whether graft perfusion truly represents tissue oxygenation, perfusion parameters will be compared with systemic lactate as well as serosal lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia related markers and mitochondrial chain respiratory rate as measured in tissue samples from the stomach graft.
Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict anastomotic leakage and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses.
Relevance: The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during EC surgery. Such a tool may help to reduce the incidence of AL and its associated severe morbidity and mortality
- Conditions
- Anastomotic Leak, Esophageal Cancer
- Being tested
- Indocyanine green angiography, Hemodynamic evaluation, Biological and pathological markers of ischemia
- Keywords
- esophagectomy, indocyanine green, near infrared fluorescence
- Medical subject headings
- Anastomotic Leak, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indocyanine green angiographyDiagnostic test
Also called near infrared fluorescent imaging
ICGA will be performed twice during standard esophagectomy: 30 minutes after the stomach graft creation and immediately before the esophagogastric anastomosis. stock dose of 25 mg ICG (Pulsion Medical Systems, Germany) will be diluted to 5 mg/mL with sterile water. An IV bolus of 0.5 mg/kg of ICG will be injected via a central venous catheter. Video data will be obtained with a charge-coupled device (CCD) camera fitted with a light-emitting diode emitting at a wavelength of 760mm (Visera® elite II, Olympus medical system corp, Tokyo, Japan). Images will be recorded starting immediately prior to injection until 3 minutes afterwards.
Hemodynamic evaluationDiagnostic test
Advanced continuous hemodynamic monitoring during surgery will be performed using a PiCCO® (Pulse index Continuous Cardiac Output, Pulsion Medical Systems, Germany) catheter.
Biological and pathological markers of ischemiaDiagnostic test
- Systemic and local capillary lactate on blood samples
- Mitochondrial Respiratory activity analyses on biopsies at 3 region of interest (ROI)
- Pathological analyses of the biopsies at 3 ROI
| Study group | Role | What they receive |
|---|---|---|
| Indocyanine Green Angiography | Experimental | ICG based angiography after creation of the stomach graft and after thoracic pull-up of the graft. Dynamic digital images will be obtained starting immediately after intravenous bolus administration of 0.5 mg/kg of ICG. Receives: Diagnostic Test: Indocyanine green angiography; Diagnostic Test: Hemodynamic evaluation; Diagnostic Test: Biological and pathological markers of ischemia |
What is being measured
The primary outcome is the main question the study is designed to answer.
An ICGA based cutoff point to predict anastomotic leakage and graft necrosis after esophageal reconstructive surgery.
quantitative analysis of the ICGA images. T inflow will be calculated based on time fluorescence curves, and correlated with anastomotic leakage and graft necrosis. This cutoff value will be an ICGA fluorescent intensity time measurement expressed in seconds.
Measured: within 3 months after intervention
Secondary outcomes (14)
The evaluation of ICGA as a quantitative perfusion imaging modality during gastric tube reconstruction.
First, intensity over time curves will be analysed in the regions of interest to generate quantitative values for maximal fluorescence intensity (I max), inflow time (T inflow), and outflow time (T outflow). For every patient a time intensity curve will be created and From that curve 3 quantitaive time measures will be extracted: for maximal fluorescence intensity (I max), inflow time (T inflow), and outflow time (T outflow). These 3 times will be expressed in seconds
Measured: within 3 months after intervention
Systemic lactate as a Biological Markers of hypoxia and ischemia
Peroperative blood samples will be collected and analyzed
Measured: within 24 hours after intervention
Capillary lactate as a Biological Markers of hypoxia and ischemia
Peroperative blood samples will be collected and analyzed
Measured: within 24 hours after intervention
Basal oxygen consumption (V0) as a Biological Markers of hypoxia and ischemia
Peroperative biopsies will be collected and analyzed
Measured: within 24 hours after intervention
Max respiratory oxygen consumption (Vmax) as a Biological Markers of hypoxia and ischemia
Peroperative biopsies will be collected and analyzed
Measured: within 24 hours after intervention
Severity of inflammation score as a pathological Markers of hypoxia and ischemia
Peroperative biopsies will be collected and analyzed. Four sections of the embedded material are examined using a Haematoxylin-eosin staining. A semiquantitive scoring based on presence of fibroblasts, polynuclear neutrophils, lymphocytes and macrophages will be used to evaluate the severity of the inflammation. Scoring system.
Score 0 = normal mucosa Score 1: partial epithelial edema and necrosis Score 2: diffuse swelling and necrosis of the epithelium Score 3: necrosis with submucosal neutrophil infiltration Score 4: widespread necrosis and massive neutrophil infiltration and bleeding
Measured: within 10 days after intervention
HIF 1 alpha as a pathological Markers of hypoxia and ischemia
Peroperative biopsies will be collected and analyzed
Measured: within 10 days after intervention
Minor and major adverse events up to 30 days postoperative associated with esophagectomy
All adverse events will be classified by the Clavien Dindo score and based on the ECCG international consensus for complications associated with esophagectomy guidelines.The list is a predefined by the ECCG and can be found in reference 32.
Measured: within 1 year after intervention
Product related adverse endpoints
- Anaphylactic adverse events (AE): discomfort, flushing, tachycardia, hypotension, dyspnoea, bronchial spasm, blushing, cardiac arrest, laryngeal spasm, and facial oedema.
- Urticarial AE: pruritus, urticaria
- Nausea.
- hypereosinophilia
Measured: within 24 hours after intervention
Intensive Care Unit (ICU) stay
duration of intensive care stay expressed in days
Measured: within 1 year after intervention
in hospital stay
duration of the in hospital stay expressed in days
Measured: within 1 year after intervention
cardiac output
Advanced continuous hemodynamic monitoring during surgery will be performed using a PiCCO® (Pulse index Continuous Cardiac Output, Pulsion Medical Systems, Germany). This will provide specific perfusion measurements as cardiac output expressed in liters per minute from the Pulse contour analysis and Thermo dilution analysis.
Measured: within 24 hours after the intervention
Stroke Volume
Advanced continuous hemodynamic monitoring during surgery will be performed using a PiCCO® (Pulse index Continuous Cardiac Output, Pulsion Medical Systems, Germany). This will provide specific perfusion measurements as Stroke Volume (SV) expressed in milliliter and stroke volume variation (SVV) to predict Volume responsivity by Pulse contour analysis and Thermo dilution analysis.
Measured: within 24 hours after the intervention
pulse pressure
Advanced continuous hemodynamic monitoring during surgery will be performed using a PiCCO® (Pulse index Continuous Cardiac Output, Pulsion Medical Systems, Germany). This will provide specific perfusion measurements as pulse pressure (PP) expressed in millimeters of mercury (mmHg) and pulse pressure variation (PPV) to predict volume responsivity by Pulse contour analysis.
Measured: within 24 hours after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2018
- Study start13 Dec 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Anastomotic LeakStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- Kom Op Tegen Kanker
- Responsible party
- Sponsor
- Investigators
- Yves Yves.Vannieuwenhove@uzgent.be, MD, PhD, Study director, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03587532
- Sponsor's protocol ID
- EC/2018/0671
- Acronym
- EDOBS
- Status last verified
- Dec 2023
- First submitted
- 14 Jun 2018
- Last updated
- 28 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kassis ES, Kosinski AS, Ross P Jr, Koppes KE, Donahue JM, Daniel VC. Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg. 2013 Dec;96(6):1919-26. doi: 10.1016/j.athoracsur.2013.07.119. Epub 2013 Sep 24.
PubMed 24075499Biere SS, Maas KW, Cuesta MA, van der Peet DL. Cervical or thoracic anastomosis after esophagectomy for cancer: a systematic review and meta-analysis. Dig Surg. 2011;28(1):29-35. doi: 10.1159/000322014. Epub 2011 Feb 4.
PubMed 21293129Sauvanet A, Mariette C, Thomas P, Lozac'h P, Segol P, Tiret E, Delpero JR, Collet D, Leborgne J, Pradere B, Bourgeon A, Triboulet JP. Mortality and morbidity after resection for adenocarcinoma of the gastroesophageal junction: predictive factors. J Am Coll Surg. 2005 Aug;201(2):253-62. doi: 10.1016/j.jamcollsurg.2005.02.002.
PubMed 16038824Sunpaweravong S, Ruangsin S, Laohawiriyakamol S, Mahattanobon S, Geater A. Prediction of major postoperative complications and survival for locally advanced esophageal carcinoma patients. Asian J Surg. 2012 Jul;35(3):104-9. doi: 10.1016/j.asjsur.2012.04.029. Epub 2012 Jun 6.
PubMed 22884266Haga Y, Wada Y, Takeuchi H, Ikejiri K, Ikenaga M. Prediction of anastomotic leak and its prognosis in digestive surgery. World J Surg. 2011 Apr;35(4):716-22. doi: 10.1007/s00268-010-0922-5.
PubMed 21184072Rutegard M, Lagergren P, Rouvelas I, Lagergren J. Intrathoracic anastomotic leakage and mortality after esophageal cancer resection: a population-based study. Ann Surg Oncol. 2012 Jan;19(1):99-103. doi: 10.1245/s10434-011-1926-6. Epub 2011 Jul 19.
PubMed 21769467Van Daele E, Van de Putte D, Ceelen W, Van Nieuwenhove Y, Pattyn P. Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomydagger. Interact Cardiovasc Thorac Surg. 2016 Jan;22(1):32-7. doi: 10.1093/icvts/ivv276. Epub 2015 Oct 3.
PubMed 26433973Wright CD, Kucharczuk JC, O'Brien SM, Grab JD, Allen MS; Society of Thoracic Surgeons General Thoracic Surgery Database. Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. J Thorac Cardiovasc Surg. 2009 Mar;137(3):587-95; discussion 596. doi: 10.1016/j.jtcvs.2008.11.042.
PubMed 19258071Junemann-Ramirez M, Awan MY, Khan ZM, Rahamim JS. Anastomotic leakage post-esophagogastrectomy for esophageal carcinoma: retrospective analysis of predictive factors, management and influence on longterm survival in a high volume centre. Eur J Cardiothorac Surg. 2005 Jan;27(1):3-7. doi: 10.1016/j.ejcts.2004.09.018.
PubMed 15621463Markar SR, Arya S, Karthikesalingam A, Hanna GB. Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis. Ann Surg Oncol. 2013 Dec;20(13):4274-81. doi: 10.1245/s10434-013-3189-x. Epub 2013 Aug 14.
PubMed 23943033Alander JT, Kaartinen I, Laakso A, Patila T, Spillmann T, Tuchin VV, Venermo M, Valisuo P. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi: 10.1155/2012/940585. Epub 2012 Apr 22.
PubMed 22577366Milstein DMJ, Ince C, Gisbertz SS, Boateng KB, Geerts BF, Hollmann MW, van Berge Henegouwen MI, Veelo DP. Laser speckle contrast imaging identifies ischemic areas on gastric tube reconstructions following esophagectomy. Medicine (Baltimore). 2016 Jun;95(25):e3875. doi: 10.1097/MD.0000000000003875.
PubMed 27336874Linder G, Hedberg J, Bjorck M, Sundbom M. Perfusion of the gastric conduit during esophagectomy. Dis Esophagus. 2017 Jan 1;30(1):143-149. doi: 10.1111/dote.12537.
PubMed 27766735Pham TH, Perry KA, Enestvedt CK, Gareau D, Dolan JP, Sheppard BC, Jacques SL, Hunter JG. Decreased conduit perfusion measured by spectroscopy is associated with anastomotic complications. Ann Thorac Surg. 2011 Feb;91(2):380-5. doi: 10.1016/j.athoracsur.2010.10.006.
PubMed 21256274Tsekov C, Belyaev O, Tcholakov O, Tcherveniakov A. Intraoperative Doppler assessment of gastric tube perfusion in esophagogastroplasty. J Surg Res. 2006 May;132(1):98-103. doi: 10.1016/j.jss.2005.07.037. Epub 2005 Sep 12.
PubMed 16154594
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Graft Perfusion and Oxygenation for Improved Outcome in Esophageal Cancer Surgery
- ClinicalTrials.gov ID
- NCT03587532
- Acronym / sponsor ID
- EDOBS / EC/2018/0671
- Conditions
- Anastomotic Leak, Esophageal Cancer
- Keywords
- esophagectomy, indocyanine green, near infrared fluorescence
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- Kom Op Tegen Kanker
- Study start
- 13 Dec 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 16 Jul 2018 (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.
After the esophagectomy, the stomach is most commonly used to restore continuity of the upper gastro-intestinal tract. The esophagogastric anastomosis is prone to serious complications such as anastomotic leakage (AL) The reported incidence of AL after esophagectomy ranges from 5%-20%. The AL associated mortality ranges from 18-40% compared with an overall in-hospital mortality of 4-6%. The main cause of AL is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft. Clinical judgment is unreliable in determining anastomotic perfusion. Therefore, an objective, validated, and reproducible method to evaluate tissue perfusion at the anastomotic site is urgently needed. Indocyanine green angiography (ICGA) is a near infrared fluorescent (NIRF) perfusion imaging using indocyanine green (ICG). ICGA is a safe, easy and reproducible method for graft perfusion analysis, but it is not yet calibrated. The purpose of this study is to evaluate the feasibility of quantification of ICGA to assess graft perfusion and its influence on AL in patients after minimally invasive Ivor Lewis esophagectomy (MIE) for cancer.
Detailed description
Background: The incidence of adenocarcinoma of the esophagus is rapidly increasing, resulting in 480 000 newly diagnosed patients annually in the world1. Surgery remains the cornerstone of therapy for curable esophageal cancer (EC) patients. After the esophagectomy, the stomach is most commonly used to restore continuity of the upper gastro-intestinal tract. The esophagogastric anastomosis is prone to serious complications such as anastomotic leakage (AL), fistula, bleeding, and stricture. The reported incidence of AL after esophagectomy ranges from 5%-20% 2-6. The AL associated mortality ranges from 18-40% compared with an overall in-hospital mortality of 4-6% 2, 7, 8. The main cause of AL is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft. Clinical judgment is unreliable in determining anastomotic perfusion. Therefore, an objective, validated, and reproducible method to evaluate tissue perfusion at the anastomotic site is urgently needed. Near infrared fluorescent (NIRF) perfusion imaging using indocyanine green (ICG) is an emerging modality based on excitation and resulting fluorescence in the near-infrared range (λ = 700-900 nm).
Aims:
- To perform intraoperative ICG based NIRF angiography of the stomach graft during minimally invasive esophagectomy in EC patients, and to calculate tissue blood flow and volume using curve analysis and advanced compartmental modeling;
- To validate imaging based perfusion parameters by comparison with hemodynamic parameters, blood and tissue expression of hypoxia induced markers, and tissue mitochondrial respiration rate
- To evaluate the ability of NIRF based perfusion measurement to predict anastomotic leakage.
Methods: Patients (N=70) with resectable EC will be recruited to undergo minimally invasive Ivor Lewis esophagectomy according to the current standard of care. ICG based angiography will be performed after creation of the stomach graft and after thoracic pull-up of the graft. Dynamic digital images will be obtained starting immediately after intravenous bolus administration of 0.5 mg/kg of ICG. The resulting images will be subjected to curve analysis (time to peak, washout time) and to compartmental analysis based on the AATH kinetic model (adiabatic approximation to tissue homogeneity, which allows to calculate blood flow, blood volume, vascular heterogeneity, and vascular leakage). The calculated perfusion parameters will be compared to intraoperative hemodynamic data (PiCCO catheter) to evaluate how patient hemodynamics affect graft perfusion. To verify whether graft perfusion truly represents tissue oxygenation, perfusion parameters will be compared with systemic lactate as well as serosal lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia related markers and mitochondrial chain respiratory rate as measured in tissue samples from the stomach graft.
Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict anastomotic leakage and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses.
Relevance: The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during EC surgery. Such a tool may help to reduce the incidence of AL and its associated severe morbidity and mortality
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Indocyanine Green Angiography | Experimental | Diagnostic Test: Indocyanine green angiography, Diagnostic Test: Hemodynamic evaluation, Diagnostic Test: Biological and pathological markers of ischemiaICG based angiography after creation of the stomach graft and after thoracic pull-up of the graft. Dynamic digital images will be obtained starting immediately after intravenous bolus administration of 0.5 mg/kg of ICG. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Pre- and intraoperatively
- Subjects ≥ 18 years and ≤ 75 years who are willing to participate and provide written informed consent prior to any study-related procedures.
- Subjects scheduled for elective minimally invasive Ivor Lewis esophagectomy
- Intrathoracic circular stapled esophago-gastric anastomosis
Key exclusion criteria (9 listed)
- Preoperatively
- Known hypersensitivity to ICG
- Female patients who are pregnant or nursing
- Participation in other studies involving investigational drugs or devices.
- Use of Avastin™ (bevacizumab) or other anti vascular endothelial growth factor (VEGF) agents within 30 days prior to surgery
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 |
|---|---|---|
| Indocyanine green angiographyAlso: near infrared fluorescent imagingICGA will be performed twice during standard esophagectomy: 30 minutes after the stomach graft creation and immediately before the esophagogastric anastomosis. stock dose of 25 mg ICG (Pulsion Medical Systems, Germany) will be diluted to 5 mg/mL with sterile water. An IV bolus of 0.5 mg/kg of ICG will be injected via a central venous catheter. Video data will be obtained with a charge-coupled device (CCD) camera fitted with a light-emitting diode emitting at a wavelength of 760mm (Visera® elite II, Olympus medical system corp, Tokyo, Japan). Images will be recorded starting immediately prior to injection until 3 minutes afterwards. | Diagnostic test | Indocyanine Green Angiography |
| Hemodynamic evaluationAdvanced continuous hemodynamic monitoring during surgery will be performed using a PiCCO® (Pulse index Continuous Cardiac Output, Pulsion Medical Systems, Germany) catheter. | Diagnostic test | Indocyanine Green Angiography |
| Biological and pathological markers of ischemia* Systemic and local capillary lactate on blood samples * Mitochondrial Respiratory activity analyses on biopsies at 3 region of interest (ROI) * Pathological analyses of the biopsies at 3 ROI | Diagnostic test | Indocyanine Green Angiography |
Primary outcome
An ICGA based cutoff point to predict anastomotic leakage and graft necrosis after esophageal reconstructive surgery.
Time frame: within 3 months after intervention
quantitative analysis of the ICGA images. T inflow will be calculated based on time fluorescence curves, and correlated with anastomotic leakage and graft necrosis. This cutoff value will be an ICGA fluorescent intensity time measurement expressed in seconds.
14 secondary outcomes
The evaluation of ICGA as a quantitative perfusion imaging modality during gastric tube reconstruction.
Time frame: within 3 months after intervention
Systemic lactate as a Biological Markers of hypoxia and ischemia
Time frame: within 24 hours after intervention
Capillary lactate as a Biological Markers of hypoxia and ischemia
Time frame: within 24 hours after intervention
Basal oxygen consumption (V0) as a Biological Markers of hypoxia and ischemia
Time frame: within 24 hours after intervention
Max respiratory oxygen consumption (Vmax) as a Biological Markers of hypoxia and ischemia
Time frame: within 24 hours after intervention
Severity of inflammation score as a pathological Markers of hypoxia and ischemia
Time frame: within 10 days after intervention
HIF 1 alpha as a pathological Markers of hypoxia and ischemia
Time frame: within 10 days after intervention
Minor and major adverse events up to 30 days postoperative associated with esophagectomy
Time frame: within 1 year after intervention
Product related adverse endpoints
Time frame: within 24 hours after intervention
Intensive Care Unit (ICU) stay
Time frame: within 1 year after intervention
in hospital stay
Time frame: within 1 year after intervention
cardiac output
Time frame: within 24 hours after the intervention
Stroke Volume
Time frame: within 24 hours after the intervention
pulse pressure
Time frame: within 24 hours after the intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2023.
- Background: PubMed 24075499Kassis ES, Kosinski AS, Ross P Jr, Koppes KE, Donahue JM, Daniel VC. Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg. 2013 Dec;96(6):1919-26. doi: 10.1016/j.athoracsur.2013.07.119. Epub 2013 Sep 24.
- Background: PubMed 21293129Biere SS, Maas KW, Cuesta MA, van der Peet DL. Cervical or thoracic anastomosis after esophagectomy for cancer: a systematic review and meta-analysis. Dig Surg. 2011;28(1):29-35. doi: 10.1159/000322014. Epub 2011 Feb 4.
- Background: PubMed 16038824Sauvanet A, Mariette C, Thomas P, Lozac'h P, Segol P, Tiret E, Delpero JR, Collet D, Leborgne J, Pradere B, Bourgeon A, Triboulet JP. Mortality and morbidity after resection for adenocarcinoma of the gastroesophageal junction: predictive factors. J Am Coll Surg. 2005 Aug;201(2):253-62. doi: 10.1016/j.jamcollsurg.2005.02.002.
- Background: PubMed 22884266Sunpaweravong S, Ruangsin S, Laohawiriyakamol S, Mahattanobon S, Geater A. Prediction of major postoperative complications and survival for locally advanced esophageal carcinoma patients. Asian J Surg. 2012 Jul;35(3):104-9. doi: 10.1016/j.asjsur.2012.04.029. Epub 2012 Jun 6.
- Background: PubMed 21184072Haga Y, Wada Y, Takeuchi H, Ikejiri K, Ikenaga M. Prediction of anastomotic leak and its prognosis in digestive surgery. World J Surg. 2011 Apr;35(4):716-22. doi: 10.1007/s00268-010-0922-5.
- Background: PubMed 21769467Rutegard M, Lagergren P, Rouvelas I, Lagergren J. Intrathoracic anastomotic leakage and mortality after esophageal cancer resection: a population-based study. Ann Surg Oncol. 2012 Jan;19(1):99-103. doi: 10.1245/s10434-011-1926-6. Epub 2011 Jul 19.
- Background: PubMed 26433973Van Daele E, Van de Putte D, Ceelen W, Van Nieuwenhove Y, Pattyn P. Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomydagger. Interact Cardiovasc Thorac Surg. 2016 Jan;22(1):32-7. doi: 10.1093/icvts/ivv276. Epub 2015 Oct 3.
- Background: PubMed 19258071Wright CD, Kucharczuk JC, O'Brien SM, Grab JD, Allen MS; Society of Thoracic Surgeons General Thoracic Surgery Database. Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. J Thorac Cardiovasc Surg. 2009 Mar;137(3):587-95; discussion 596. doi: 10.1016/j.jtcvs.2008.11.042.
- Background: PubMed 15621463Junemann-Ramirez M, Awan MY, Khan ZM, Rahamim JS. Anastomotic leakage post-esophagogastrectomy for esophageal carcinoma: retrospective analysis of predictive factors, management and influence on longterm survival in a high volume centre. Eur J Cardiothorac Surg. 2005 Jan;27(1):3-7. doi: 10.1016/j.ejcts.2004.09.018.
- Background: PubMed 23943033Markar SR, Arya S, Karthikesalingam A, Hanna GB. Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis. Ann Surg Oncol. 2013 Dec;20(13):4274-81. doi: 10.1245/s10434-013-3189-x. Epub 2013 Aug 14.
- Background: PubMed 22577366Alander JT, Kaartinen I, Laakso A, Patila T, Spillmann T, Tuchin VV, Venermo M, Valisuo P. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi: 10.1155/2012/940585. Epub 2012 Apr 22.
- Background: PubMed 27336874Milstein DMJ, Ince C, Gisbertz SS, Boateng KB, Geerts BF, Hollmann MW, van Berge Henegouwen MI, Veelo DP. Laser speckle contrast imaging identifies ischemic areas on gastric tube reconstructions following esophagectomy. Medicine (Baltimore). 2016 Jun;95(25):e3875. doi: 10.1097/MD.0000000000003875.
- Cancer Statistics, GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. International Agency for Research on Cancer, WHO.Link provided by the sponsor.
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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.
Yves Yves.Vannieuwenhove@uzgent.be, MD, PhD study director
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Indocyanine green angiography, Hemodynamic evaluation and Biological and pathological markers of ischemia in people with Anastomotic Leak and Esophageal Cancer, run by University Hospital, Ghent at 1 site in Belgium.
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 9 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 28 Dec 2023. 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 Belgium. 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 Elke Van Daele, MD (+323320829, elke.vandaele@uzgent.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
An ICGA based cutoff point to predict anastomotic leakage and graft necrosis after esophageal reconstructive surgery. (time frame: within 3 months after intervention). 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 NCT03587532, which also lists 25 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 28 Dec 2023.