FrostbitePhase 4ECCONCT07424378
Epoprostenol Plus Conventional Therapy in COld and Frostbite Injury (ECCO)
A Phase 4 study of Frostbite, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
Severe frostbite injury can result in significant lifelong disability and amputation. Various medicines, including intravenous vasodilators (prostaglandins/iloprost, pentoxifylline, buflomedil) along with thrombolytics (alteplase), have been described to counter tissue ischemia after rewarming, with poor quality of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Frostbite
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2026to Nov 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Aged ≥ 18 years
- Admitted to University of Colorado Hospital (UCH) Burn and Frostbite Center
- Cauchy Grade 2-4 frostbite injury
- Admission within 72 hours post-rewarming
Who cannot join
- Patients unable to initiate therapy within 72 hours post-rewarming
- Unsalvageable frostbite as defined by obvious necrosis of tissue, wet gangrene, or other condition requiring amputation (within the first week)
- Anticipated death within 48 hours of admission
- Pregnant or breastfeeding patients
- Prisoners
- Inability to obtain consent from patient or legally authorized representative (LAR) or proxy
Show all 13Show fewer
- Not a good candidate for treatment per treating physician or investigator
- Patients with known allergy/hypersensitivity to epoprostenol
- Current or planned receipt of other prostaglandin analog (iloprost and treprostinil)
- Known congestive heart failure due to severe left ventricular systolic dysfunction (New York Heart Association (NYHA) class III/IV)
- Known right heart failure (RHF)
- Hypotension unresponsive to fluids and discontinuation of concomitant anti-hypertensives (mean arterial pressure (MAP) < 65 mmHg)
- Known pulmonary hypertension
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
University of Colorado, Denver
Aurora, Colorado, 80045
Beth A Strimpel, M.A, BSN, RN, 203-980-2209, beth.a.strimpel@cuanschutz.edu
Erin L Anderson, RN, 720-999-8760, erin.l.anderson@cuanschutz.edu
University of Colorado, Denver
Aurora, Colorado, 80045
About this study
Official title: Randomized Controlled Trial of Epoprostenol Versus Placebo in Addition to Standard Therapy for Severe Frostbite Injury
Severe frostbite injury can result in significant lifelong disability and amputation. Various medicines, including intravenous vasodilators (prostaglandins/iloprost, pentoxifylline, buflomedil) along with thrombolytics (alteplase), have been described to counter tissue ischemia after rewarming, with poor quality of evidence. An in-class prostacyclin, epoprostenol, has similar pharmacodynamic properties to iloprost including vasodilation and platelet inhibition and has been used in peripheral tissue ischemia such as Raynaud's and scleroderma. In this trial, we will evaluate the effectiveness and safety of epoprostenol treatment for severe frostbite injury in addition to standard of care.
Read the detailed description
Prospective single center placebo controlled randomized trial comparing epoprostenol versus placebo in patients already receiving the standard of care for frostbite, including alteplase. Hypothesis: treatment effect of epoprostenol will be greater than placebo, independent of prior alteplase administration. Standard of care in both groups includes immediate warm water rewarming, thrombolysis with alteplase if they are a thrombolytic candidate per our usual care, immediate therapeutic anticoagulation if received thrombolysis, and ibuprofen at the attending physician's discretion.
Study Aim: To determine the efficacy and safety of treatment with epoprostenol versus placebo in adult patients with severe frostbite injury.
Intervention Group: Standard of care plus epoprostenol intravenous infusion titrated based on tolerability for 5 days.
Control Group: Standard of care plus placebo (normal saline) infusion dosed and titrated to match epoprostenol infusion for 5 days.
- Conditions
- Frostbite
- Being tested
- Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximum, Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximum
- Keywords
- Frostbite, Epoprostenol, Prostaglandin, Amputation
- Medical subject headings
- Frostbite
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximumDrug
An in-class prostacyclin, epoprostenol (originally derived prostaglandin), has similar pharmacodynamic properties to Iloprost including vasodilation and platelet inhibition, is widely available and already stocked at most hospitals for already approved indications (pulmonary hypertension). Epoprostenol has advantageous pharmacokinetics including organ independent elimination, a shorter half-life allowing for a faster "off-set" of action, and decades of experience of use for other indications. This randomized controlled trial will assess the efficacy and safety of epoprostenol for frostbite in addition to our standard of care treatment for frostbite: rewarming and qualified early thrombolytic therapy.
Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximumDrug
The placebo or Normal saline will be given exactly the same as the intervention drug - via intravenous infusion for 8 hours a day up to 5 days maximum. Vital signs and monitoring will be the same. The packaging will be labeled "study medication" (epoprostenol or placebo) and neither the participant, treating clinicians, or study personnel will be able to tell the difference as both epoprostenol and normal saline have identical color, general appearance, and viscosity.
| Study group | Role | What they receive |
|---|---|---|
| Epoprostenol | Active comparator | Standard of care plus epoprostenol intravenous infusion titrated based on tolerability for 8 hours per day and up to 5 days of treatment. Receives: Drug: Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximum |
| Placebo (Normal Saline) | Placebo comparator | Standard of care plus placebo infusion dosed and titrated to match epoprostenol infusion for 8 hours per day and up to 5 days of treatment. Receives: Drug: Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amputation Rate
Amputation rate within 90 days of frostbite injury, defined as number of amputations per number of digits affected.
Measured: from enrollment to the end of treatment when client returns for clinic visit at 90 days.
Secondary outcomes (4)
Hennepin frostbite score change
The Hennepin Frostbite score is a standardized, clinical tool used to quantify injury and tissue loss of frostbite injury. It assigns a numerical value to each digit, phalanx or limb affected, based on clinical appearance or absence of blood flow. The scale is classified from 0 to 3.
0 = absence of uptake
- low uptake
- normal uptake
- high uptake Studies show patients with an absence (0) or low (1) uptake predicted amputation with high specificity.
Change in Hennepin Frostbite Score from admission to final healing to day 90
Measured: from admission to final healing to day 90
Preserved Digit Segments
Number of preserved digit segments from admission to final healing to day 90.
Measured: from admission to final healing to Day 90
Change in Perfusion Imaging (fluorescence intravenous indocyanine green)
Change in perfusion imaging from admission to final imaging. SPY Portable Handheld Imaging System (SPY -PHI) fluorescence intravenous imaging is a near-infrared (NIR) imaging technology using indocyanine green (ICG) dye to provide real-time, high-resolution visualization of blood flow, tissue perfusion, and lymphatic vessels. It enables physicians to immediately assess tissue viability and vascularity.
Physicians select a region of interest of uninjured tissue as baseline perfusion (for example 100%), and then a relative percentage value (0-100%) is obtained for affected tissue. Studies have identified a perfusion cut-off value of 33% (using SPY-QP) to determine tissue viability, with some studies showing a high negative predictive value (up to 91-93%) for identifying ischemic tissue. Data on affected tissue perfusion and location will be serially recorded every other day throughout the treatment period. A higher score means a better outcome.
Measured: from admission to final imaging at day 7
Change in Technetium Bone Scans
Technetium-99m bone scans for frostbite measure tissue perfusion, viability, and deep-tissue/bone infarction. They use a triple-phase technique to distinguish viable from necrotic (dead) tissue, providing early prognosis, identifying regions suitable for thrombolytic therapy, and determining the necessary amputation level.
These scans are superior to initial clinical exams, which may not show true tissue damage for weeks.
The scale we are using ranges from 5 options - worst outcome is completely absent perfusion, then decreased activity/perfusion, questionable or possible decreased activity, hyperfusion/increased blood flow, to the best possible outcome, which is no abnormality/no problems.
Measured: from admission to final imaging at day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study startFeb 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for FrostbiteStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participant will be randomized to either intervention or placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Arek J Wiktor, MD, FACS, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07424378
- Sponsor's protocol ID
- 25-0256
- Other IDs
- MT24001.345
- Acronym
- ECCO
- Status last verified
- Feb 2026
- First submitted
- 28 Jan 2026
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be shared with Department of Defense
Publications
Endorf FW, Nygaard RM. Social Determinants of Poor Outcomes Following Frostbite Injury: A Study of the National Inpatient Sample. J Burn Care Res. 2021 Nov 24;42(6):1261-1265. doi: 10.1093/jbcr/irab115.
PubMed 34139760Update: Cold weather injuries, active and reserve components, U.S. Armed Forces, July 2016-June 2021. MSMR. 2021 Oct 1;28(10):2-10.
PubMed 34964583Nygaard RM, Endorf FW. Frostbite in the United States: An Examination of the National Burn Repository and National Trauma Data Bank. J Burn Care Res. 2018 Aug 17;39(5):780-785. doi: 10.1093/jbcr/irx048.
PubMed 29931369Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S, Barst RJ, Barrett PS, Kral KM, Jobsis MM, Loyd JE, Murali S, Frost A, Girgis R, Bourge RC, Ralph DD, Elliott CG, Hill NS, Langleben D, Schilz RJ, McLaughlin VV, Robbins IM, Groves BM, Shapiro S, Medsger TA Jr. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000 Mar 21;132(6):425-34. doi: 10.7326/0003-4819-132-6-200003210-00002.
PubMed 10733441Young A, Namas R, Dodge C, Khanna D. Hand Impairment in Systemic Sclerosis: Various Manifestations and Currently Available Treatment. Curr Treatm Opt Rheumatol. 2016 Sep;2(3):252-269. doi: 10.1007/s40674-016-0052-9. Epub 2016 Jul 19.
PubMed 28018840Kowal-Bielecka O, Landewe R, Avouac J, Chwiesko S, Miniati I, Czirjak L, Clements P, Denton C, Farge D, Fligelstone K, Foldvari I, Furst DE, Muller-Ladner U, Seibold J, Silver RM, Takehara K, Toth BG, Tyndall A, Valentini G, van den Hoogen F, Wigley F, Zulian F, Matucci-Cerinic M; EUSTAR Co-Authors. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009 May;68(5):620-8. doi: 10.1136/ard.2008.096677. Epub 2009 Jan 15.
PubMed 19147617Del Galdo F, Lescoat A, Conaghan PG, Bertoldo E, Colic J, Santiago T, Suliman YA, Matucci-Cerinic M, Gabrielli A, Distler O, Hoffmann-Vold AM, Castellvi I, Balbir-Gurman A, Vonk M, Ananyeva L, Rednic S, Tarasova A, Ostojic P, Boyadzhieva V, El Aoufy K, Farrington S, Galetti I, Denton CP, Kowal-Bielecka O, Mueller-Ladner U, Allanore Y. EULAR recommendations for the treatment of systemic sclerosis: 2023 update. Ann Rheum Dis. 2025 Jan;84(1):29-40. doi: 10.1136/ard-2024-226430. Epub 2025 Jan 2.
PubMed 39874231Sitbon O, Vonk Noordegraaf A. Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017 Jan 17;26(143):160055. doi: 10.1183/16000617.0055-2016. Print 2017 Jan.
PubMed 28096285McIntosh SE, Freer L, Grissom CK, Auerbach PS, Rodway GW, Cochran A, Giesbrecht GG, McDevitt M, Imray CH, Johnson EL, Pandey P, Dow J, Hackett PH. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2019 Update. Wilderness Environ Med. 2019 Dec;30(4S):S19-S32. doi: 10.1016/j.wem.2019.05.002. Epub 2019 Jul 17.
PubMed 31326282Bello JW, Rickrode GA, Harlan NP, Buckey JC. Systemic Prostacyclin Analogues for Frostbite Require Careful Monitoring. J Burn Care Res. 2023 Mar 2;44(2):487-488. doi: 10.1093/jbcr/irac178. No abstract available.
PubMed 36444642Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lanteri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005 Mar;114(1-2):29-36. doi: 10.1016/j.pain.2004.12.010. Epub 2005 Jan 26.
PubMed 15733628Tan G, Jensen MP, Thornby JI, Shanti BF. Validation of the Brief Pain Inventory for chronic nonmalignant pain. J Pain. 2004 Mar;5(2):133-7. doi: 10.1016/j.jpain.2003.12.005.
PubMed 15042521Kamstra RJM, Boorsma A, Krone T, van Stokkum RM, Eggink HM, Peters T, Pasman WJ. Validation of the Mobile App Version of the EQ-5D-5L Quality of Life Questionnaire Against the Gold Standard Paper-Based Version: Randomized Crossover Study. JMIR Form Res. 2022 Aug 11;6(8):e37303. doi: 10.2196/37303.
PubMed 35969437Ogawa A, Matsubara H, Fujio H, Miyaji K, Nakamura K, Morita H, Saito H, Kusano KF, Emori T, Date H, Ohe T. Risk of alveolar hemorrhage in patients with primary pulmonary hypertension--anticoagulation and epoprostenol therapy. Circ J. 2005 Feb;69(2):216-20. doi: 10.1253/circj.69.216.
PubMed 15671616Lindford A, Valtonen J, Hult M, Kavola H, Lappalainen K, Lassila R, Aho P, Vuola J. The evolution of the Helsinki frostbite management protocol. Burns. 2017 Nov;43(7):1455-1463. doi: 10.1016/j.burns.2017.04.016. Epub 2017 Aug 1.
PubMed 28778759
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Epoprostenol Versus Placebo in Addition to Standard Therapy for Severe Frostbite Injury
- ClinicalTrials.gov ID
- NCT07424378
- Acronym / sponsor ID
- ECCO / 25-0256
- Conditions
- Frostbite
- Keywords
- Frostbite, Epoprostenol, Prostaglandin, Amputation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Feb 2026 (estimated)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 20 Feb 2026 (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.
Severe frostbite injury can result in significant lifelong disability and amputation. Various medicines, including intravenous vasodilators (prostaglandins/iloprost, pentoxifylline, buflomedil) along with thrombolytics (alteplase), have been described to counter tissue ischemia after rewarming, with poor quality of evidence. An in-class prostacyclin, epoprostenol, has similar pharmacodynamic properties to iloprost including vasodilation and platelet inhibition and has been used in peripheral tissue ischemia such as Raynaud's and scleroderma. In this trial, we will evaluate the effectiveness and safety of epoprostenol treatment for severe frostbite injury in addition to standard of care.
Detailed description
Prospective single center placebo controlled randomized trial comparing epoprostenol versus placebo in patients already receiving the standard of care for frostbite, including alteplase. Hypothesis: treatment effect of epoprostenol will be greater than placebo, independent of prior alteplase administration. Standard of care in both groups includes immediate warm water rewarming, thrombolysis with alteplase if they are a thrombolytic candidate per our usual care, immediate therapeutic anticoagulation if received thrombolysis, and ibuprofen at the attending physician's discretion.
Study Aim: To determine the efficacy and safety of treatment with epoprostenol versus placebo in adult patients with severe frostbite injury.
Intervention Group: Standard of care plus epoprostenol intravenous infusion titrated based on tolerability for 5 days.
Control Group: Standard of care plus placebo (normal saline) infusion dosed and titrated to match epoprostenol infusion for 5 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participant will be randomized to either intervention or placebo
| Arm | Type | Receives |
|---|---|---|
| Epoprostenol | Active comparator | Drug: Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximumStandard of care plus epoprostenol intravenous infusion titrated based on tolerability for 8 hours per day and up to 5 days of treatment. |
| Placebo (Normal Saline) | Placebo comparator | Drug: Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximumStandard of care plus placebo infusion dosed and titrated to match epoprostenol infusion for 8 hours per day and up to 5 days of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged ≥ 18 years
- Admitted to University of Colorado Hospital (UCH) Burn and Frostbite Center
- Cauchy Grade 2-4 frostbite injury
- Admission within 72 hours post-rewarming
Key exclusion criteria (13 listed)
- Patients unable to initiate therapy within 72 hours post-rewarming
- Unsalvageable frostbite as defined by obvious necrosis of tissue, wet gangrene, or other condition requiring amputation (within the first week)
- Anticipated death within 48 hours of admission
- Pregnant or breastfeeding patients
- Prisoners
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 |
|---|---|---|
| Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximumAn in-class prostacyclin, epoprostenol (originally derived prostaglandin), has similar pharmacodynamic properties to Iloprost including vasodilation and platelet inhibition, is widely available and already stocked at most hospitals for already approved indications (pulmonary hypertension). Epoprostenol has advantageous pharmacokinetics including organ independent elimination, a shorter half-life allowing for a faster "off-set" of action, and decades of experience of use for other indications. This randomized controlled trial will assess the efficacy and safety of epoprostenol for frostbite in addition to our standard of care treatment for frostbite: rewarming and qualified early thrombolytic therapy. | Drug | Epoprostenol |
| Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximumThe placebo or Normal saline will be given exactly the same as the intervention drug - via intravenous infusion for 8 hours a day up to 5 days maximum. Vital signs and monitoring will be the same. The packaging will be labeled "study medication" (epoprostenol or placebo) and neither the participant, treating clinicians, or study personnel will be able to tell the difference as both epoprostenol and normal saline have identical color, general appearance, and viscosity. | Drug | Placebo (Normal Saline) |
Primary outcome
Amputation Rate
Time frame: from enrollment to the end of treatment when client returns for clinic visit at 90 days.
Amputation rate within 90 days of frostbite injury, defined as number of amputations per number of digits affected.
4 secondary outcomes
Hennepin frostbite score change
Time frame: from admission to final healing to day 90
Preserved Digit Segments
Time frame: from admission to final healing to Day 90
Change in Perfusion Imaging (fluorescence intravenous indocyanine green)
Time frame: from admission to final imaging at day 7
Change in Technetium Bone Scans
Time frame: from admission to final imaging at day 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Background: PubMed 34139760Endorf FW, Nygaard RM. Social Determinants of Poor Outcomes Following Frostbite Injury: A Study of the National Inpatient Sample. J Burn Care Res. 2021 Nov 24;42(6):1261-1265. doi: 10.1093/jbcr/irab115.
- Background: PubMed 34964583Update: Cold weather injuries, active and reserve components, U.S. Armed Forces, July 2016-June 2021. MSMR. 2021 Oct 1;28(10):2-10.
- Background: PubMed 29931369Nygaard RM, Endorf FW. Frostbite in the United States: An Examination of the National Burn Repository and National Trauma Data Bank. J Burn Care Res. 2018 Aug 17;39(5):780-785. doi: 10.1093/jbcr/irx048.
- Background: PubMed 10733441Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S, Barst RJ, Barrett PS, Kral KM, Jobsis MM, Loyd JE, Murali S, Frost A, Girgis R, Bourge RC, Ralph DD, Elliott CG, Hill NS, Langleben D, Schilz RJ, McLaughlin VV, Robbins IM, Groves BM, Shapiro S, Medsger TA Jr. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000 Mar 21;132(6):425-34. doi: 10.7326/0003-4819-132-6-200003210-00002.
- Background: PubMed 28018840Young A, Namas R, Dodge C, Khanna D. Hand Impairment in Systemic Sclerosis: Various Manifestations and Currently Available Treatment. Curr Treatm Opt Rheumatol. 2016 Sep;2(3):252-269. doi: 10.1007/s40674-016-0052-9. Epub 2016 Jul 19.
- Background: PubMed 19147617Kowal-Bielecka O, Landewe R, Avouac J, Chwiesko S, Miniati I, Czirjak L, Clements P, Denton C, Farge D, Fligelstone K, Foldvari I, Furst DE, Muller-Ladner U, Seibold J, Silver RM, Takehara K, Toth BG, Tyndall A, Valentini G, van den Hoogen F, Wigley F, Zulian F, Matucci-Cerinic M; EUSTAR Co-Authors. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009 May;68(5):620-8. doi: 10.1136/ard.2008.096677. Epub 2009 Jan 15.
- Background: PubMed 39874231Del Galdo F, Lescoat A, Conaghan PG, Bertoldo E, Colic J, Santiago T, Suliman YA, Matucci-Cerinic M, Gabrielli A, Distler O, Hoffmann-Vold AM, Castellvi I, Balbir-Gurman A, Vonk M, Ananyeva L, Rednic S, Tarasova A, Ostojic P, Boyadzhieva V, El Aoufy K, Farrington S, Galetti I, Denton CP, Kowal-Bielecka O, Mueller-Ladner U, Allanore Y. EULAR recommendations for the treatment of systemic sclerosis: 2023 update. Ann Rheum Dis. 2025 Jan;84(1):29-40. doi: 10.1136/ard-2024-226430. Epub 2025 Jan 2.
- Background: PubMed 28096285Sitbon O, Vonk Noordegraaf A. Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017 Jan 17;26(143):160055. doi: 10.1183/16000617.0055-2016. Print 2017 Jan.
- Background: PubMed 31326282McIntosh SE, Freer L, Grissom CK, Auerbach PS, Rodway GW, Cochran A, Giesbrecht GG, McDevitt M, Imray CH, Johnson EL, Pandey P, Dow J, Hackett PH. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2019 Update. Wilderness Environ Med. 2019 Dec;30(4S):S19-S32. doi: 10.1016/j.wem.2019.05.002. Epub 2019 Jul 17.
- Background: PubMed 36444642Bello JW, Rickrode GA, Harlan NP, Buckey JC. Systemic Prostacyclin Analogues for Frostbite Require Careful Monitoring. J Burn Care Res. 2023 Mar 2;44(2):487-488. doi: 10.1093/jbcr/irac178. No abstract available.
- Background: PubMed 15733628Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lanteri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005 Mar;114(1-2):29-36. doi: 10.1016/j.pain.2004.12.010. Epub 2005 Jan 26.
- Background: PubMed 15042521Tan G, Jensen MP, Thornby JI, Shanti BF. Validation of the Brief Pain Inventory for chronic nonmalignant pain. J Pain. 2004 Mar;5(2):133-7. doi: 10.1016/j.jpain.2003.12.005.
- Veletri (epoprostenol). Package insert. Actelion Pharmaceuticals US, Inc.; 2020Link provided by the sponsor.
- Individual participant dataSharing planned: No. Data will be shared with Department of Defense
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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.
Arek J Wiktor, MD, FACS principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Frostbite, run by University of Colorado, Denver at 2 sites 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 4 inclusion and 13 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: opening soon, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Beth A Strimpel, MA, BSN, RN (203-980-2209, beth.a.strimpel@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amputation Rate (time frame: from enrollment to the end of treatment when client returns for clinic visit at 90 days.). 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 NCT07424378, which also lists 21 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 20 Feb 2026.