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

February 19, 2026 updated by: University of Colorado, Denver

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

66

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged ≥ 18 years
  2. Admitted to University of Colorado Hospital (UCH) Burn and Frostbite Center
  3. Cauchy Grade 2-4 frostbite injury
  4. Admission within 72 hours post-rewarming

Exclusion Criteria:

  1. Patients unable to initiate therapy within 72 hours post-rewarming
  2. Unsalvageable frostbite as defined by obvious necrosis of tissue, wet gangrene, or other condition requiring amputation (within the first week)
  3. Anticipated death within 48 hours of admission
  4. Pregnant or breastfeeding patients
  5. Prisoners
  6. Inability to obtain consent from patient or legally authorized representative (LAR) or proxy
  7. Not a good candidate for treatment per treating physician or investigator
  8. Patients with known allergy/hypersensitivity to epoprostenol
  9. Current or planned receipt of other prostaglandin analog (iloprost and treprostinil)
  10. Known congestive heart failure due to severe left ventricular systolic dysfunction (New York Heart Association (NYHA) class III/IV)
  11. Known right heart failure (RHF)
  12. Hypotension unresponsive to fluids and discontinuation of concomitant anti-hypertensives (mean arterial pressure (MAP) < 65 mmHg)
  13. Known pulmonary hypertension

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Epoprostenol
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
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.
Placebo Comparator: Placebo (Normal Saline)
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
from enrollment to the end of treatment when client returns for clinic visit at 90 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hennepin frostbite score change
Time Frame: from admission to final healing to day 90

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
from admission to final healing to day 90
Preserved Digit Segments
Time Frame: from admission to final healing to Day 90
Number of preserved digit segments from admission to final healing to day 90.
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 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.
from admission to final imaging at day 7
Change in Technetium Bone Scans
Time Frame: from admission to final imaging at day 7

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.
from admission to final imaging at day 7

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital Length of Stay
Time Frame: from admission to day 90
Measure the total number of days each patient spent in the hospital.
from admission to day 90
Mortality Rate
Time Frame: from admission to day 90
Measure the incidence of death within the patients admitted to the hospital, enrolled in this frostbite study, expressed as a rate or percentage.
from admission to day 90
Need for Skin graft procedures
Time Frame: from admission to 90 days of frostbite injury
The number of patients who had a skin graft
from admission to 90 days of frostbite injury
Need for Surgical Debridement
Time Frame: from admission to day 90
The number of patients who had a surgical debridement
from admission to day 90
Need for surgical excision
Time Frame: from admission to day 90.
The number of patients who had a surgical excision
from admission to day 90.
Need for surgical flap
Time Frame: from admission to day 90
The number of patients who had a surgical flap
from admission to day 90
Long term outcome- Neuropathy level
Time Frame: from admission to 90 days after frostbite injury

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.
from admission to 90 days after frostbite injury
Long term outcome: Neuropathy Level
Time Frame: from admission to 90 days after frostbite injury
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.
from admission to 90 days after frostbite injury
Functional Ability -Quick Disabilities of Arm, Shoulder, Hand (DASH)
Time Frame: from admission to 90 days after frostbite injury
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).
from admission to 90 days after frostbite injury
Functional Ability - Lower Extremity Functional Scale (LEFS)
Time Frame: from admission to 90 days after frostbite injury
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
from admission to 90 days after frostbite injury
Quality of Life - Five-level EuroQol five-dimensional questionnaire(EQ-5D-5L)
Time Frame: from admission to 90 days after frostbite injury

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).
from admission to 90 days after frostbite injury
Return to Work
Time Frame: from discharge to 90 days after frostbite injury
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.
from discharge to 90 days after frostbite injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Arek J Wiktor, MD, FACS, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

January 28, 2026

First Submitted That Met QC Criteria

February 19, 2026

First Posted (Actual)

February 20, 2026

Study Record Updates

Last Update Posted (Actual)

February 20, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25-0256
  • MT24001.345 (Other Grant/Funding Number: Medical Technology Enterprise Consortium(MTEC)/Department of Defense)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be shared with Department of Defense

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Frostbite

Clinical Trials on Standard of care plus Epoprostenol infusion for 8 hours (hrs) per day up to 5 days maximum

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Rwanda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe