Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001097336
Ethics application status
Approved
Date submitted
21/07/2017
Date registered
27/07/2017
Date last updated
26/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Near infra-red imaging of the microvasculature in comparison with resin casting of amputated limbs
Scientific title
Near infra-red imaging of the microvasculature in comparison with resin casting of amputated limbs
Secondary ID [1] 292488 0
none
Universal Trial Number (UTN)
U1111-1199-6593
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
microvenous insufficiency 304114 0
amputation of lower limb 304154 0
Condition category
Condition code
Cardiovascular 303446 303446 0 0
Diseases of the vasculature and circulation including the lymphatic system
Surgery 303487 303487 0 0
Surgical techniques

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Part one, proof of concept:
Two amputated lower limbs will be imaged with a near-infra red (NIR) camera and indocyanine green dye contrast. The imaging will involve recording the peak intensity of the fluorescence of the dye, and the time taken to peak intensity. Bright spots will be indicated and marked on the limb. After imaging, the limb will undergo resin casting, whereby resin will be injected into veins of the limb and allowed to set. This will produce a map of the micro venous system, with markers where imaging showed potential areas of reflux. The resulting resin map will be analysed to determine the degree of venous reflux in multiple regions of interest in the limb. This will be correlated with the data obtained from the NIR imaging.
Part Two: Continuation
If part one provides usable data from both imaging and resin casting, participants will be asked if they would like to undergo imaging prior to amputation, to allow for better correlation. The imaging session will take less than one hour, and involves cannulating the participant for a local injection of indocyanine green (ICG) dye. of ICG solution (0.02 mg/ml) will be injected into a vein in the foot or at the level of the ankle, for the duration of the imaging sequence . This may be possible in neuropathic patients, who do not feel pain in their limbs. Patients will only be included in this extra imaging if a vascular surgeon who is not part of the study deems it appropriate. We aim to have three more participants, and hope to have at least one who is able to undergo imaging prior to amputation.
Intervention code [1] 298667 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator treatment is resin casting of the amputated limb, and each limb will have both the imaging and the resin casting. Resin (Batson’s #17 resin, Polysciences Inc. Warrington, Pa) will be injected into the limb. As resin begins to flow from vessels at the proximal end of the limb, these vessels will be identified and ligated. Once the outflow vessels are closed, further resin will be injected until significant resistance is met. The limb will be immersed in saline for 12 hours to allow the resin to harden. Tissue will be removed by maceration in 15% sodium hydroxide (3.75 M) at 60C and the resulting cast will be analysed.
Control group
Active

Outcomes
Primary outcome [1] 302823 0
Correlation of ingress (intensity of the contrast dye from start to peak intensity) with reflux generation level of resin cast (in regions of interest). This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05.
Timepoint [1] 302823 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Primary outcome [2] 302855 0
Correlation of egress (intensity of the contrast dye from peak intensity to finish) with reflux generation level of the resin cast (in regions of interest).This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05.
Timepoint [2] 302855 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Primary outcome [3] 302856 0
Correlation of ingress rate of the contrast dye with generation level of reflux generation level of resin cast (in regions of interest),This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05.
Timepoint [3] 302856 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Secondary outcome [1] 337170 0
Correlation of egress rate of the contrast dye with generation level of reflux generation level of resin cast (in regions of interest), This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05. . This is a primary outcome.
Timepoint [1] 337170 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Secondary outcome [2] 337253 0
Correlation of time to peak intensity of the contrast dye with generation level of reflux generation level of resin cast (in regions of interest), This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05. This is a primary outcome
Timepoint [2] 337253 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Secondary outcome [3] 337254 0
Correlation of peak intensity of the contrast dye with generation level of reflux generation level of resin cast (in regions of interest), This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05. This is a primary outcome.
Timepoint [3] 337254 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Secondary outcome [4] 337255 0
Correlation of ingress rate of contrast dye with generation level of reflux generation level of resin cast (in regions of interest), This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. Each individual region of interest will be given a generation designation, and this number will be compared with the SPYQ data that is also specific to that region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05. This is a primary outcome
Timepoint [4] 337255 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.
Secondary outcome [5] 337257 0
Correlation of overall dye intensity with overall generation level of the resin casting. This is determined without specifying a region of interest, This will be assessed by first visually evaluating the image for regions of high, medium and low contrast intensity, and marking them with a permanant marker. After amputation, these spots (regions of interest) will be sutured using a polymer suture thread. Ingress will be assessed by using SPYQ software (SPY Novadaq Technologies Inc, Bonita Springs, FL). Reflux generation level will be assigned based on how many generations of valves in the venous system are incompetent. The resin can pass freely into a tributary if the valves in that tributary are incompetent, so with no incompetence, only the great saphenous vein (GSV) is mapped in the resin cast. The GSV and its tributaries are generation 0 (no venous insufficiency). Valves in subsequent tributaries will be assigned a consecutively numbered generation, up to generation 4. This number will be compared with the SPYQ data that is obtained from the overall imaging sequence.. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05.
Timepoint [5] 337257 0
Within 1 hour post amputation or 12 hours after patient death, the GSV of each limb will be cannulated with a 20 gauge needle at the level of the medial malleolus and flushed with saline. The limb will then be chilled at 4 degrees C for up to 12 hours if we are unable to do immediate imaging.
In part 2, if a participant meets the criteria for imaging prior to amputation, NIR imaging will be conducted within 2 days of amputation.

Eligibility
Key inclusion criteria
Inclusion criteria:
- patients awaiting an amputation of a lower limb.

Inclusion criteria for undergoing NIR imaging prior to amputation:
- Patient consent.
- A vascular surgeon who is not an investigator in this study determines that the imaging (prior to the amputation) will not cause undue stress or pain for the patient.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are not referred for a lower limb amputation will be excluded.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
Data from the NIR imaging (ingress, egress, ingress rate, egress rate, time to peak intensity, and peak intensity) will be compared with the level of incompetency found in regions of interest on the resin casts (Generations 0-4) within limbs and between limbs, using Prism Graph Pad (Graphpad Software, Inc. La Jolla, CA). We expect that a diseased limb with a generation of 4 will allow 4 regions in which NIR imaging can be compared with the resin casts. Each individual region will be given a generation designation, and this number will be compared with the imaging data that is also specific to each region. Spearman’s rank correlation coefficients will be used to reflect the degree of relationships between variables. Significance will be indicated by two-sided p<0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
27/09/2018
Actual
Date of last participant enrolment
Anticipated
30/08/2019
Actual
Date of last data collection
Anticipated
30/08/2019
Actual
Sample size
Target
6
Accrual to date
Final
Recruitment outside Australia
Country [1] 9077 0
New Zealand
State/province [1] 9077 0
Otago

Funding & Sponsors
Funding source category [1] 297056 0
Hospital
Name [1] 297056 0
Dunedin Public Hospital
Country [1] 297056 0
New Zealand
Primary sponsor type
Hospital
Name
Dunedin Public Hospital
Address
201 Great King St, Dunedin, 9016
Country
New Zealand
Secondary sponsor category [1] 296061 0
None
Name [1] 296061 0
Address [1] 296061 0
Country [1] 296061 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298240 0
Health and Disabilities Ethics Committee NZ
Ethics committee address [1] 298240 0
Ethics committee country [1] 298240 0
New Zealand
Date submitted for ethics approval [1] 298240 0
03/08/2017
Approval date [1] 298240 0
12/06/2018
Ethics approval number [1] 298240 0
NZ/1/EDAF014

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1899 1899 0 0
/AnzctrAttachments/373346-NIR amputated limb protocol.docx (Protocol)
Attachments [2] 1900 1900 0 0
/AnzctrAttachments/373346-Patient Information Sheet limb study proof of concept.docx (Participant information/consent)
Attachments [3] 1901 1901 0 0
/AnzctrAttachments/373346-Patient Information Sheet limb study.docx (Participant information/consent)

Contacts
Principal investigator
Name 76442 0
Mrs Jo Krysa
Address 76442 0
University of Otago
Department of Surgical Sciences
Dunedin School of Medicine
201 Great King St, Dunedin, 9016
Country 76442 0
New Zealand
Phone 76442 0
+64, 3-474 0999 ext. 8835
Fax 76442 0
Email 76442 0
[email protected]
Contact person for public queries
Name 76443 0
Kari Clifford
Address 76443 0
University of Otago
Department of Surgical Sciences
Dunedin School of Medicine
201 Great King St, Dunedin, 9016
Country 76443 0
New Zealand
Phone 76443 0
+64, 3-474 0999 ext. 8835
Fax 76443 0
Email 76443 0
[email protected]
Contact person for scientific queries
Name 76444 0
Kari Clifford
Address 76444 0
University of Otago
Department of Surgical Sciences
Dunedin School of Medicine
201 Great King St, Dunedin, 9016
Country 76444 0
New Zealand
Phone 76444 0
+64, 3-474 0999 ext. 8835
Fax 76444 0
Email 76444 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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