Epoprostenol Plus Conventional Therapy in COld and Frostbite Injury (ECCO)

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 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.

Timeline

Start

2026-02

Primary completion

2028-11

Completion

2028-11

Publications

• Background 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.
• Background Update: Cold weather injuries, active and reserve components, U.S. Armed Forces, July 2016-June 2021. MSMR. 2021 Oct 1;28(10):2-10.
• Background Nygaard 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 Badesch 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 Young 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 Kowal-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 Del 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 Sitbon 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 McIntosh 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 Bello 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 Bouhassira 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 Tan 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.
• Background Kamstra 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.
• Background Ogawa 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.
• Background Lindford 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.
• Background Murphy J, Endorf FW, Winters MK, Rogers C, Walter E, Neumann N, Weber L, Lacey AM, Punjabi G, Nygaard RM. Bleeding Complications in Patients With Severe Frostbite Injury. J Burn Care Res. 2023 Jul 5;44(4):745-750. doi: 10.1093/jbcr/irac180.
• Background Poole A, Gauthier J, MacLennan M. Management of severe frostbite with iloprost, alteplase and heparin: a Yukon case series. CMAJ Open. 2021 May 21;9(2):E585-E591. doi: 10.9778/cmajo.20200214. Print 2021 Apr-Jun.
• Background Crooks S, Shaw BH, Andruchow JE, Lee CH, Walker I. Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study. CJEM. 2022 Sep;24(6):622-629. doi: 10.1007/s43678-022-00342-9. Epub 2022 Jul 23.
• Background Cauchy E, Cheguillaume B, Chetaille E. A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med. 2011 Jan 13;364(2):189-90. doi: 10.1056/NEJMc1000538. No abstract available.
• Background Cauchy E, Davis CB, Pasquier M, Meyer EF, Hackett PH. A New Proposal for Management of Severe Frostbite in the Austere Environment. Wilderness Environ Med. 2016 Mar;27(1):92-9. doi: 10.1016/j.wem.2015.11.014.
• Background Wibbenmeyer L, Lacey AM, Endorf FW, Logsetty S, Wagner ALL, Gibson ALF, Nygaard RM. American Burn Association Clinical Practice Guidelines on the Treatment of Severe Frostbite. J Burn Care Res. 2024 May 6;45(3):541-556. doi: 10.1093/jbcr/irad022.

Drugs

Indications

No indication recorded.