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

ConditionFrostbite
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Colorado, Denver

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

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

    Drug

    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 maximum

    Drug

    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.

Treatment groups

66 Participants
are divided into 2 treatment groups
Group A: EpoprostenolActive comparator 1 intervention
Group B: Placebo (Normal Saline)Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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.

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

1

Hospital Length of Stay

Measure the total number of days each patient spent in the hospital.

Time frame
from admission to day 90
2

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
3

Need for Skin graft procedures

The number of patients who had a skin graft

Time frame
from admission to 90 days of frostbite injury
4

Need for Surgical Debridement

The number of patients who had a surgical debridement

Time frame
from admission to day 90

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Colorado, Denver

Lead sponsor

United States Department of Defense

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: