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FrostbiteNCT05777590

Comparison of ICG Microangiography and Conventional Angiography in Severe Frostbite

An observational study of Frostbite, run by HealthPartners Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Severe frostbite injury is a significant cause of morbidity in northern climates. Minnesota has some of the highest numbers of severe frostbite injuries in North America. As a result, Regions Hospital has the best opportunity to study this disease process and improve outcomes for frostbite patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Frostbite
What is being tested?
Indocyanine Green Angiogram
How many people
8 participants
Where
1 siteUnited States
Study dates
3 Feb 2023to 3 Jun 2026
Phase
Observational
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
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients undergoing conventional angiography and thrombolysis for severe frostbite. will be identified by the burn surgeons and advance practice practitioners. They will evaluate the patients to determine whether they meet the inclusion/exclusion criteria of the study.

Who may be able to join

  • Adult (>18 years old) patients
  • Diagnosed with severe frostbite by conventional angiography
  • Undergoing thrombolysis with catheter directed lytics
  • Clinically sober at the time of consent
  • Cognitively able to provide consent as determined by clinician's best judgement
  • Normal kidney function (GFR >60)

Who cannot join

  • Pregnant. Pregnancy will be determined by standard of care pregnancy test performed on all female frostbite patients who are receiving lytics.
  • Iodine allergy.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Regions Hospital

    Saint Paul, Minnesota, 55101

Other trials in United States

About this study

Official title: Prospective Comparison of ICG Microangiography and Conventional Angiography in Severe Frostbite

Severe frostbite injury is a significant cause of morbidity in northern climates. Minnesota has some of the highest numbers of severe frostbite injuries in North America. As a result, Regions Hospital has the best opportunity to study this disease process and improve outcomes for frostbite patients. The diagnostic methods for severe frostbite injury vary from institution to institution and there is no standard practice. Commonly utilized methods include conventional angiography, Technetium 99 triple phase bone scans, SPECT studies, Indocyanine Green microangiography, and doppler studies. The proposed pilot study aims to directly compare conventional angiography imaging to ICG microangiography in adult patients with severe frostbite. Severe frostbite is defined as 4th degree: frostbite resulting in vascular occlusion and tissue ischemia. Both imaging modalities have been used for the diagnosis and monitoring of severe frostbite injury but there has never been a study directly comparing these two imaging modalities.

Read the detailed description

Frostbite injury has been a significant cause of morbidity and mortality for as long as humans have experienced cold winters. When frostbite occurs, there are two primary mechanisms through which tissue damage occurs, though the main mechanism focused on here is systemic cooling. Frostbite is a multiphase process that starts with systemic cooling. As the body cools, blood is shunted from the extremities to the core to maintain heat in the vital organs. During this shunting, there is extensive vasospasm in the extremities and the tissue becomes ischemic. Upon further cooling, tissue ice crystals form within the cells and interstitial spaces causing desiccation and cell destruction. This occurs in the soft tissues and also affects the endothelium of the micro- and macro-vasculature. Clots form in the microvasculature, worsening the ischemia. All ischemic tissues release pro-inflammatory factors, which increase inflammation and worsen clotting.

Upon rewarming of the frozen tissues, the reperfusion can worsen the inflammatory state as these factors released by the ischemic tissue are now able to circulate. Rapid rewarming is used as a tool to mitigate this reperfusion injury, but it does not eliminate the damage. After rapid rewarming, the tissue is assessed for the extent of damage to determine next treatment steps. Diagnosis varies by institution, but the main goal of all diagnostic modalities is to determine if there is a vascular cutoff causing tissue ischemia.

At Regions Hospital, the main diagnostic method that has been used for over 20 years is conventional angiography. This clearly demonstrates the microvasculature of the tissues and allows the intra-arterial catheter directed sheaths to be placed to start thrombolytics, heparin, and vasodilators to treat the tissue ischemia. Other diagnostic modalities used elsewhere include Technetium 99 triple phase bone scans, SPECT imaging, and indocyanine green (ICG) microangiography. All of these imaging modalities demonstrate the perfusion of the affected tissue but do not allow for directed delivery of thrombolytics. In institutions that use these imaging techniques, thrombolytics are typically delivered in an intravenous fashion rather than intra-arterial.

ICG microangiography is a technology that has had rapidly expanding applications in recent decades. These have included retinal imaging, determining perfusion of colorectal anastomoses, biliary imaging, and assessing the blood supply of tissue flaps. It has recently been used in diagnosis of frostbite with good correlation with severe final amputation levels. It is easy to use, non-radiating, can be performed at the bedside, and cheaper than other imaging modalities.

Given that every hospital has different diagnostic and treatment algorithms, these different imaging modalities have rarely been compared in the same patient. The current best metric is comparing the imaging modality with the amount of tissue that is amputated as demonstrated in prior studies cited here. This research application provides a unique opportunity to compare two imaging modalities head-to-head in the same patient and determine their concordance or discordance.

Conditions
Frostbite
Being tested
Indocyanine Green Angiogram
Keywords
Frostbite, Angiogram, Indocyanine Green, ICG
Medical subject headings
Frostbite

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Indocyanine Green AngiogramDrug

    Also called ICG

    Angiogram using ICG dye the occurs directly after conventional angiogram in assessment of frostbite patients undergoing thrombolysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of Angiography and ICG microangiography imaging demonstrating ischemic tissue present in severe frostbite scored by Hennepin Frostbite Score.

    Hypothesize that these two imaging modalities (ICG (indocyanine green) and conventional angiography) will be concordant at demonstrating the ischemic tissue present in severe frostbite.

    Measured: Through study completion, an average of 2 years

Secondary outcomes (1)
  1. Safety of indocyanine green when delivered in close association with contrast dye (used in conventional angiography) measured by number of adverse events

    Contrast dye used in conventional angiography is associated with nephrotoxicity and other risks. Indocyanine green dye is generally considered to be a highly safe product with minimal risks associated with administration. It has been used for decades with minimal side effects. It is hypothesized that ICG dye will not result in any increase in risk to the patient when delivered in temporal proximity to conventional dye.

    Measured: Through study completion, an average of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2023
  2. Study start3 Feb 2023
  3. Primary completion1 Feb 2025
  4. Study completion3 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05777590
Sponsor's protocol ID
A22-321
Status last verified
Jul 2026
First submitted
14 Jan 2023
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lacey AM, Rogers C, Endorf FW, Fey RM, Gayken JR, Schmitz KR, Punjabi GV, Whitley AB, Masters TC, Moore JC, Nygaard RM. An Institutional Protocol for the Treatment of Severe Frostbite Injury-A 6-Year Retrospective Analysis. J Burn Care Res. 2021 Aug 4;42(4):817-820. doi: 10.1093/jbcr/irab008.

    PubMed 33484248
  • Gonzaga T, Jenabzadeh K, Anderson CP, Mohr WJ, Endorf FW, Ahrenholz DH. Use of Intra-arterial Thrombolytic Therapy for Acute Treatment of Frostbite in 62 Patients with Review of Thrombolytic Therapy in Frostbite. J Burn Care Res. 2016 Jul-Aug;37(4):e323-34. doi: 10.1097/BCR.0000000000000245.

    PubMed 25950290
  • Gao Y, Wang F, Zhou W, Pan S. Research progress in the pathogenic mechanisms and imaging of severe frostbite. Eur J Radiol. 2021 Apr;137:109605. doi: 10.1016/j.ejrad.2021.109605. Epub 2021 Feb 17.

    PubMed 33621855
  • Millet JD, Brown RK, Levi B, Kraft CT, Jacobson JA, Gross MD, Wong KK. Frostbite: Spectrum of Imaging Findings and Guidelines for Management. Radiographics. 2016 Nov-Dec;36(7):2154-2169. doi: 10.1148/rg.2016160045. Epub 2016 Aug 5.

    PubMed 27494386
  • Twomey JA, Peltier GL, Zera RT. An open-label study to evaluate the safety and efficacy of tissue plasminogen activator in treatment of severe frostbite. J Trauma. 2005 Dec;59(6):1350-4; discussion 1354-5. doi: 10.1097/01.ta.0000195517.50778.2e.

    PubMed 16394908
  • Heard J, Shamrock A, Galet C, Pape KO, Laroia S, Wibbenmeyer L. Thrombolytic Use in Management of Frostbite Injuries: Eight Year Retrospective Review at a Single Institution. J Burn Care Res. 2020 May 2;41(3):722-726. doi: 10.1093/jbcr/iraa028.

    PubMed 32030427
  • Masters T, Omodt S, Gayken J, Logue C, Westgard B, Hendriksen S, Walter J, Nygaard R. Microangiography to Monitor Treatment Outcomes Following Severe Frostbite Injury to the Hands. J Burn Care Res. 2018 Jan 1;39(1):162-167. doi: 10.1097/BCR.0000000000000526.

    PubMed 28328661
  • Lacey AM, Fey RM, Gayken JR, Endorf FW, Schmitz KR, Punjabi GV, Masters TC, Nygaard RM. Microangiography: An Alternative Tool for Assessing Severe Frostbite Injury. J Burn Care Res. 2019 Aug 14;40(5):566-569. doi: 10.1093/jbcr/irz112.

    PubMed 31298700
  • WEATHERLEY-WHITE RC, SJOSTROM B, PATON BC. EXPERIMENTAL STUDIES IN COLD INJURY. II. THE PATHOGENESIS OF FROSTBITE. J Surg Res. 1964 Jan;4:17-22. doi: 10.1016/s0022-4804(64)80004-4. No abstract available.

    PubMed 14106388
  • Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation cascade. Crit Care Med. 1992 Oct;20(10):1402-5. doi: 10.1097/00003246-199210000-00007.

    PubMed 1395660
  • Zook N, Hussmann J, Brown R, Russell R, Kucan J, Roth A, Suchy H. Microcirculatory studies of frostbite injury. Ann Plast Surg. 1998 Mar;40(3):246-53; discussion 254-5. doi: 10.1097/00000637-199803000-00009.

    PubMed 9523607
  • Bourne MH, Piepkorn MW, Clayton F, Leonard LG. Analysis of microvascular changes in frostbite injury. J Surg Res. 1986 Jan;40(1):26-35. doi: 10.1016/0022-4804(86)90141-1.

    PubMed 3941548
  • Robson MC, Heggers JP. Evaluation of hand frostbite blister fluid as a clue to pathogenesis. J Hand Surg Am. 1981 Jan;6(1):43-7. doi: 10.1016/s0363-5023(81)80010-x.

    PubMed 7204918
  • McCauley RL, Hing DN, Robson MC, Heggers JP. Frostbite injuries: a rational approach based on the pathophysiology. J Trauma. 1983 Feb;23(2):143-7.

    PubMed 6827634
  • Rogers C, Lacey AM, Endorf FW, Punjabi G, Whitley A, Gayken J, Fey R, Schmitz K, Nygaard RM. The Effects of Rapid Rewarming on Tissue Salvage in Severe Frostbite Injury. J Burn Care Res. 2022 Jul 1;43(4):906-911. doi: 10.1093/jbcr/irab218.

    PubMed 34791315

Questions about this trial

What is this clinical trial studying?

An observational study of Frostbite, run by HealthPartners Institute at 1 site in United States.

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 6 inclusion and 2 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 30 Jul 2026. 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 States. 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?

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?

Assessment of Angiography and ICG microangiography imaging demonstrating ischemic tissue present in severe frostbite scored by Hennepin Frostbite Score. (time frame: Through study completion, an average of 2 years). 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 NCT05777590, which also lists 19 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 30 Jul 2026.

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