A Phase 4 interventional study of Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximum and Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximum in Frostbite, sponsored by University of Colorado, Denver. Not yet recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-20.
Sponsored by University of Colorado, Denver · Phase 4, Interventional, and Treatment
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.
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.
University of Colorado, Denver is the lead sponsor of 1,499 studies on the registry; 315 are open to participants now.
Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Standard of care plus epoprostenol intravenous infusion titrated based on tolerability for 8 hours per day and up to 5 days of treatment.
Drug: Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximum
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.
Drug: Standard of Care + Placebo (Normal Saline)infusion for 8 hours per day up to 5 days maximum
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.
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.
Amputation Rate
Amputation rate within 90 days of frostbite injury, defined as number of amputations per number of digits affected.
Time frame: from enrollment to the end of treatment when client returns for clinic visit at 90 days.
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 1. low uptake 2. normal uptake 3. 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
Time frame: from admission to final healing to day 90
Preserved Digit Segments
Number of preserved digit segments from admission to final healing to day 90.
Time frame: 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.
Time frame: 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.
Time frame: from admission to final imaging at day 7
Hospital Length of Stay
Measure the total number of days each patient spent in the hospital.
Time frame: from admission to day 90
Mortality Rate
Measure the incidence of death within the patients admitted to the hospital, enrolled in this frostbite study, expressed as a rate or percentage.
Time frame: from admission to day 90
Need for Skin graft procedures
The number of patients who had a skin graft
Time frame: from admission to 90 days of frostbite injury
Need for Surgical Debridement
The number of patients who had a surgical debridement
Time frame: from admission to day 90
Need for surgical excision
The number of patients who had a surgical excision
Time frame: from admission to day 90.
Need for surgical flap
The number of patients who had a surgical flap
Time frame: from admission to day 90
Long term outcome- Neuropathy level
The level of neuropathy as measured by the Qualitative Sensory Test(QST), performed at Day 90 after frostbite injury. The QST is a psychophysical test that assesses sensory nerve function by measuring a person's ability to detect stimuli such as heat, cold and vibration. It is used to detect nerve damage or dysfunction after frostbite. The TSA2Air devise is a hand- held device used to measure sensory nerve function. Generally, at the onset of a stimulus, an adaptation temperature between 30°C and 32°C is set (within this range, the subject should have neither a warm sensation or a cool sensation). For threshold measurement, temperature will then decrease or increase at a constant rate until a response from the subject or operator is received. Response can be recorded by either using the keyboard (operator or subject) or the Patient Response Unit (subject). The temperature at which the response was noted is saved, and the next cycle of stimuli starts.
Time frame: from admission to 90 days after frostbite injury
Long term outcome: Neuropathy Level
The Neuropathic Pain Diagnostic Questionnaire (DN4) is a questionnaire that measures the presence and severity of neuropathy on a scale from 0 to 10. Ten questions are asked. A yes answer is 1 point, and a no answer is 0 points. The lower the score, the better the outcome. This questionnaire is given at the Burn Clinic return visit, 90 days after frostbite injury.
Time frame: from admission to 90 days after frostbite injury
Functional Ability -Quick Disabilities of Arm, Shoulder, Hand (DASH)
The Quick DASH questionnaire for arms and shoulders and hand mobility. Each question has a scale rating from No difficulty, mild difficulty, moderate difficulty, severe difficulty, or unable to do task. It also asks about pain levels ranging from none (0), mild (1), moderate (2), severe (3) to extreme (4).
Time frame: from admission to 90 days after frostbite injury
Functional Ability - Lower Extremity Functional Scale (LEFS)
The Lower Extremity Functional Scale (LEFS) is a questionnaire that scores for all 20 items to get a total score between 0 and 80. Each item is scored on a 5-point scale from 0 (extreme difficulty or unable to perform) to 4 (no difficulty). A higher LEFS score indicates better lower extremity function
Time frame: from admission to 90 days after frostbite injury
Quality of Life - Five-level EuroQol five-dimensional questionnaire(EQ-5D-5L)
The EQ-5D-5L is a generic health questionnaire that measures health-related quality of life by asking respondents to rate their current health status across five dimensions: * mobility, * self-care, * usual activities, * pain/discomfort, and * anxiety/depression. For each dimension, respondents choose from five (5) levels of severity, indicating no, slight, moderate, severe, or extreme problems. The questionnaire also includes a visual analogue scale (VAS), where individuals rate their overall health from 0 (worst possible) to 100 (best possible).
Time frame: from admission to 90 days after frostbite injury
Return to Work
Return to work is a yes/no question determining if the subject has returned to work (if working prior to hospitalization) at day 90 after discharge. The answers provided are yes, no, did not work/attend school previously or unknown.
Time frame: from discharge to 90 days after frostbite injury
Plan to share: No — Data will be shared with Department of Defense
This study is not yet recruiting, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Frostbite
University of Colorado, Denver