ChylothoraxPhase 1/2FLOTORNCT03292757
FLOTOR Pilot Study
A Phase 1/2 study testing Indocyanine Green in people with Chylothorax and Esophageal Cancer, run by Oxford University Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
This is a non-randomised study assessing the technique of using indocyanine green as a fluorescent dye to highlight the thoracic duct during oesophectomy. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chylothorax, Esophageal Cancer, Thoracic Duct Intra-Operative Injury
- What is being tested?
- Indocyanine Green
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Dec 2017to 20 Sep 2018
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Undergoing elective oesophagectomy
Who cannot join
- Known allergy to iodine or ICG
- Female patient who is pregnant, planning pregnancy or breastfeeding
- Patient has a lactose intolerance (excluded only from receiving cream method)
- Known significant liver failure
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Upper GI Surgery, Oxford University Hospitals
Headington, Oxfordshire, OX3 7LE
About this study
Official title: FLuOrescence to Identify the Thoracic Duct During Oesophageal Resections
This is a non-randomised study assessing the technique of using indocyanine green as a fluorescent dye to highlight the thoracic duct during oesophectomy.
Read the detailed description
The thoracic duct is the largest vessel of the lymphatic system in the body. It transports chyle (a liquid containing both lymph and emulsified fats) from most of the body, including the gastrointestinal tract, into the left internal jugular vein. It is largely located in the thorax and is at risk of injury during the thoracic part of an oesophagectomy.
The reported incidence of thoracic duct injury during oesophagectomy is between 0.2 and 10.5%, although it may be under-reported in the literature. A review of prospective collected complication data from 292 consecutive oesophagectomies performed in Oxford over a 5 year period revealed a chyle leak rate of 9.9%. Chyle leak was associated in a doubling of median length of post-operative stay from 8 to 16 days in these patients. Chylothorax has been associated with a mortality of up to 30%.
Over the years, a number of attempts have been made to visualise chyle leakage following thoracic duct injury including administration of enteral fat containing feed (e.g. double cream), methylene blue and lymphoscintigraphy, but no studies have been published showing a mechanism to aid thoracic duct identification at the index operation, and so prevent injuries.
Fluorescence is a technique which uses fluorescent dyes (fluorophores) that emit invisible (near infra-red (NIR)) light when they are excited by light at a particular wavelength. In order to use this technique, a fluorescence-enabled camera is required in order to shine light at that particular wavelength on the fluorophore and to capture the light emitted. This is then displayed on a screen for the surgeon to see.
Indocyanine green (ICG) is a fluorescent molecule that is approved by the FDA (Food and Drug Administration) and the MHRA for use in humans. It is a widely used near infra-red dye for numerous operations. Near infra-red guided lymphatic mapping with ICG has gained much attention over recent years and its use has widely been published in breast and colorectal surgery. ICG has also been successfully used to identify the thoracic duct in a number of case reports in both adults and children.
ICG can be injected into the small bowel mesentery to aid identification of thoracic duct injury at re-exploration. This study aims to assess the feasibility of using ICG fluorescence to identify the thoracic duct during oesophagectomy, with the eventual aim of developing its routine use to prevent thoracic duct injuries.
- Being tested
- Indocyanine Green
- Keywords
- Fluorescence
- Medical subject headings
- Chylothorax, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indocyanine GreenDrug
Also called ICG
Fluorescent dye - indocyanine green
| Study group | Role | What they receive |
|---|---|---|
| Mesenteric ICG | Experimental | Indocyanine green injected into the small bowel mesentery during oesophagectomy. Receives: Drug: Indocyanine Green |
| Feeding jejunostomy ICG (cream) | Experimental | Indocyanine green mixed with cream infiltrated into the feeding jejunostomy. Receives: Drug: Indocyanine Green |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of thoracic ducts seen under fluorescence versus number of thoracic ducts seen with white light. (Change over time)
Thoracic duct visualised fluorescence assessment
Measured: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose
Secondary outcomes (2)
Signal to background ratio of fluorescence in thoracic ducts between 2 methods of ICG administration.
Thoracic duct fluorescence levels between methods of ICG administration
Measured: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose
Signal to background ratio of fluorescence in thoracic ducts between dosing levels.
Thoracic duct fluorescence levels between ICG doses
Measured: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start20 Dec 2017
- Primary completion20 Aug 2018
- Study completion20 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ChylothoraxStudies 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 1/2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Barnes, Oxford University Hospitals NHS Trust
- Investigators
- Richard Gillies, MBChB, Principal investigator, Consultant Upper GI SurgeonThomas Barnes, MBChB, Principal investigator, Clinical Research Fellow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03292757
- Sponsor's protocol ID
- 12968
- Acronym
- FLOTOR
- Status last verified
- Nov 2018
- First submitted
- 18 Sep 2017
- Last updated
- 19 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share individual participant data
Publications
Barnes TG, MacGregor T, Sgromo B, Maynard ND, Gillies RS. Near infra-red fluorescence identification of the thoracic duct to prevent chyle leaks during oesophagectomy. Surg Endosc. 2022 Jul;36(7):5319-5325. doi: 10.1007/s00464-021-08912-1. Epub 2021 Dec 14.
PubMed 34905086
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FLuOrescence to Identify the Thoracic Duct During Oesophageal Resections
- ClinicalTrials.gov ID
- NCT03292757
- Acronym / sponsor ID
- FLOTOR / 12968
- Keywords
- Fluorescence
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Oxford University Hospitals NHS TrustUniversity, hospital or other
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 20 Aug 2018 (actual)
- Study completion
- 20 Sep 2018 (actual)
- First posted
- 26 Sep 2017 (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.
This is a non-randomised study assessing the technique of using indocyanine green as a fluorescent dye to highlight the thoracic duct during oesophectomy.
Detailed description
The thoracic duct is the largest vessel of the lymphatic system in the body. It transports chyle (a liquid containing both lymph and emulsified fats) from most of the body, including the gastrointestinal tract, into the left internal jugular vein. It is largely located in the thorax and is at risk of injury during the thoracic part of an oesophagectomy.
The reported incidence of thoracic duct injury during oesophagectomy is between 0.2 and 10.5%, although it may be under-reported in the literature. A review of prospective collected complication data from 292 consecutive oesophagectomies performed in Oxford over a 5 year period revealed a chyle leak rate of 9.9%. Chyle leak was associated in a doubling of median length of post-operative stay from 8 to 16 days in these patients. Chylothorax has been associated with a mortality of up to 30%.
Over the years, a number of attempts have been made to visualise chyle leakage following thoracic duct injury including administration of enteral fat containing feed (e.g. double cream), methylene blue and lymphoscintigraphy, but no studies have been published showing a mechanism to aid thoracic duct identification at the index operation, and so prevent injuries.
Fluorescence is a technique which uses fluorescent dyes (fluorophores) that emit invisible (near infra-red (NIR)) light when they are excited by light at a particular wavelength. In order to use this technique, a fluorescence-enabled camera is required in order to shine light at that particular wavelength on the fluorophore and to capture the light emitted. This is then displayed on a screen for the surgeon to see.
Indocyanine green (ICG) is a fluorescent molecule that is approved by the FDA (Food and Drug Administration) and the MHRA for use in humans. It is a widely used near infra-red dye for numerous operations. Near infra-red guided lymphatic mapping with ICG has gained much attention over recent years and its use has widely been published in breast and colorectal surgery. ICG has also been successfully used to identify the thoracic duct in a number of case reports in both adults and children.
ICG can be injected into the small bowel mesentery to aid identification of thoracic duct injury at re-exploration. This study aims to assess the feasibility of using ICG fluorescence to identify the thoracic duct during oesophagectomy, with the eventual aim of developing its routine use to prevent thoracic duct injuries.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesenteric ICG | Experimental | Drug: Indocyanine GreenIndocyanine green injected into the small bowel mesentery during oesophagectomy. |
| Feeding jejunostomy ICG (cream) | Experimental | Drug: Indocyanine GreenIndocyanine green mixed with cream infiltrated into the feeding jejunostomy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Undergoing elective oesophagectomy
Key exclusion criteria (4 listed)
- Known allergy to iodine or ICG
- Female patient who is pregnant, planning pregnancy or breastfeeding
- Patient has a lactose intolerance (excluded only from receiving cream method)
- Known significant liver failure
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 GreenAlso: ICGFluorescent dye - indocyanine green | Drug | Feeding jejunostomy ICG (cream), Mesenteric ICG |
Primary outcome
Number of thoracic ducts seen under fluorescence versus number of thoracic ducts seen with white light. (Change over time)
Time frame: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose
Thoracic duct visualised fluorescence assessment
2 secondary outcomes
Signal to background ratio of fluorescence in thoracic ducts between 2 methods of ICG administration.
Time frame: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose
Signal to background ratio of fluorescence in thoracic ducts between dosing levels.
Time frame: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2018.
- Derived from this study: PubMed 34905086Barnes TG, MacGregor T, Sgromo B, Maynard ND, Gillies RS. Near infra-red fluorescence identification of the thoracic duct to prevent chyle leaks during oesophagectomy. Surg Endosc. 2022 Jul;36(7):5319-5325. doi: 10.1007/s00464-021-08912-1. Epub 2021 Dec 14.
- Individual participant dataSharing planned: No. No plan to share individual participant data
Related trials for Chylothorax
Recruiting
Olive Oil Before Lung Cancer Surgery to Prevent Chylothorax
Lung Cancer, Chylothorax
RecruitingObservational study
European Registry Study on Lymphatic Interventions
Lymphatic Disorders, Plastic Bronchitis
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.
Richard Gillies, MBChB principal investigator
Consultant Upper GI Surgeon
Thomas Barnes, MBChB principal investigator
Clinical Research Fellow
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Indocyanine Green in people with Chylothorax and Esophageal Cancer, run by Oxford University Hospitals NHS Trust at 1 site in United Kingdom.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 19 Nov 2018. 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 United Kingdom. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of thoracic ducts seen under fluorescence versus number of thoracic ducts seen with white light. (Change over time) (time frame: 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 180, 240 minutes post dose). 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 NCT03292757, which also lists 1 linked publication.
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 19 Nov 2018.