Field Study on Intravenous Iloprost for Treatment of Severe Frostbite at High Altitude (HAI-Frost)

High-Altitude Iloprost Feasibility Study for Treatment of Frostbite

The goal of this observational study is to learn whether intravenous iloprost treatment for severe frostbite (grades 3-4) is feasible and safe when delivered in pre-hospital, remote high-altitude settings.

The main questions it aims to answer are:

• Is it feasible to initiate and deliver guideline-based intravenous iloprost for grade 3-4 frostbite at high altitude and what logistical barriers arise?
• Does field-based initiation of iloprost increase tissue preservation and reduce amputations (compared to historical cases from similar settings)?

Participants receiving Iloprost as part of a frostbite treatment will be followed up after discharge as well as 6, 12 and 18 months to assess tissue preservation and long-term sequelae from the initial frostbite injury.

Study Overview

• Status: Not yet recruiting
• Conditions: Frostbite; Altitude; Field Physician Care
• Intervention / Treatment: Drug: Iloprost (Ilomedin, BAYQ6256)

Detailed Description

This is a research project looking into the feasibility of frostbite treatment with iloprost in remote high altitude locations. This is an observational study. Rationale Frostbite is a significant risk for climbers and trekkers at high altitude, often resulting in long- term disability. Iloprost, a prostacyclin analogue, has shown promise in reducing amputation rates when administered intravenously within 72 hours of frostbite injury. Treatment delays are frequent due to the remoteness of climbing / trekking sites and limited access to medical facilities capable of administering iloprost. Each hour of treatment delay correlates with decreased digit salvage rates. Helicopter evacuations, commonly required to access such facilities, are often impossible or delayed due to harsh weather conditions, potentially compromising patient outcomes. We hypothesize that treatment for frostbites grade 3 & 4 with iloprost is feasible and safe in pre-hospital, high-altitude settings and can contribute to ensuring treatment initiation within the recommended time frame. We anticipate a comparable incidence and severity of side effects to iloprost treatments facilitated in clinical settings. Our primary objective is to systematically evaluate the feasibility and safety of iloprost treatment under high-altitude field conditions. This assessment will encompass the analysis of logistical challenges and the practicality of iloprost use in remote and extreme environments. Outline This prospective field study aims to assess the feasibility and safety of iloprost administration for severe frostbite at high-altitude at Everest Basecamp, Nepal (5364m). The research will be conducted during the peak climbing seasons of 2026 and 2027, targeting adult patients (aged 18 and older) presenting with frostbite grades 3 or 4 according to the Cauchy visual grading scale. Method After obtaining written informed consent, patients will receive intravenous iloprost according to current clinical guidelines, ideally within 72 hours after thawing. Throughout the study practical challenges of administering advanced medical therapy in remote, resource-limited environments will be documented. Adverse effects associated with iloprost monitored for and treated as required. Data will be collected on participant demographics, injury characteristics, time to rewarming, time to treatment, drug administration details, and side effects, as well as short-term clinical outcomes such as tissue preservation and functional status upon discharge / further referral for treatment continuation in Kathmandu. If fewer than ten eligible cases are recruited in the first two years, the study will extend for an additional season to achieve its objectives. Whenever possible, follow-up assessments will be conducted to evaluate longer-term recovery and need for amputation. Outcomes will be compared with historical data from similar high-altitude environments to estimate the potential benefit of on-site iloprost treatment. Discussion By systematically evaluating the feasibility and safety of field-based iloprost administration for frostbite, this study seeks to generate actionable evidence for improving emergency care protocols in remote and extreme environments. The findings have the potential to reduce morbidity and healthcare costs associated with frostbite, inform future wilderness medicine guidelines, and improve outcomes for climbers and high-altitude workers worldwide.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Lea AJ Duempelmann; Phone Number: +39 0471 055 726; Email: lea.duempelmann@eurac.edu

Study Locations

• Italy
  • BZ
    • Bolzano, BZ, Italy, 39100
      • Eurac research, Institute of mountain emergency medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals presenting to Everest ER with frostbites during peak climbing seasons will be evaluated and undergo grading according to Cauchy classification. If they present with grades 3 or 4 frostbite(s) they will be offered to participate.

Description

Inclusion Criteria:

• Frostbite grade 3/4 eligible for Iloprost
• <72h of thawing
• min. age of 18 years
• provision of written informed consent

Exclusion Criteria:

• age <18 years
• general contraindication
• pregnancy
• inability/denial to provide informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of frostbite presentations with severe frostbite (Grade 3-4) at Everest ER	Patients will be assessed using Cauchy classification. Proportion of patients presenting with grade 3 + 4 frostbite in relation to the total number of patients with frostbite presenting at Everest ER Unit/format: proportion (%)	from enrolment to the end of treatment at 1 week
Proportion of eligible severe frostbite patients who complete ≥1 field iloprost treatment round	The proportion of the number of patients who successfully completed at least one round of iloprost treatment under field conditions in relation to the number of eligible patients. Denominator explicitly: eligible grade 3-4 patients (Cauchy classification) Unit/format: proportion (%)	From enrolment to 1 week after beginning of treatment
Time from thawing to initiation of iloprost treatment under field conditions	Unit/format: time (hours or minutes)	From enrolment to the end of treatment at day 1
Proportion of iloprost-treated patients with mild adverse effects during/after ≥1 treatment round in the field setting	Unit/format: proportion (%) Adverse effects will be graded using CTCAE (CTCAE = Common Terminology Criteria for Adverse Events) severity criteria. Proportion of mild adverse effects in the field setting will then be compared with in-hospital settings.	From enrollment to the end of treatment at 1 week
Proportion of iloprost-treated patients with severe adverse effects during/after ≥1 treatment round in the field	Unit/format: proportion (%) Adverse effects will be graded using CTCAE (Common Terminology Criteria for Adverse Events) severity criteria. In a second step proportion of severe adverse events during field treatment will be compared with proportions of in-hospital treatment	From enrolment to the end of treatment at 1 week
Proportion of patients discontinuing field iloprost treatment (overall) and documented reasons for discontinuation	Proportion of discontinued field treatments in relation to all initiated field treatments. Unit/format: proportion (%) + categorical reason counts	From enrolment to end of treatment at 1 week
Proportion of iloprost treatment discontinuations attributable to adverse effects in the field	Unit/format: proportion (%) Number of treatments discontinued due to adverse reactions in relation to all treatments discontinued (both in the field)	From enrolment to end of treatment at 1 week
Qualitative description of logistical constraints and solutions from field notes and staff reports	Notes and reports will be analysed using a thematic analysis approach to categorise logistical challenges. Reported as: themes/categories with illustrative summaries (qualitative)	From enrolment to end of treatment at 1 week
Frequency of logistical challenges during field iloprost implementation	Number of logistical challenges, classified using a logistical challenge themes arising from qualitative analysis of field notes and staff reports. Possible themes expected include challenges related to equipment availability or functionality, personnel issues, environmental barriers. Reported as: counts (n) and percentages (%) (number of challenges within one respective category in relation to all registered logistical challenges)	from enrolment to end of treatment at 1 week
Proportion of logistical challenges resolved during the study period	Number of logistical challenges resolved in relation to all challenges recorded within one defined logistical challenge theme. Reported as: percentage (%) The logistical challenges themes will be arising from qualitative analysis of field notes and staff reports.	from enrolment to end of treatment at week 1
Mean (SD) time from thawing to first iloprost administration (clinical charts/notes), stratified by logistical challenge status (none vs occurred), resolution status (resolved vs unresolved), and challenge category	Time-to-treatment in the field will be calculated as the elapsed time between the documented thawing time and the documented start time of the first iloprost administration, as recorded in clinical charts/notes. Each case will be classified by logistical challenge status (no challenge vs challenge occurred). For cases with a challenge, resolution status will be recorded as resolved during the study period vs unresolved/persisting, and challenges will also be assigned to a logistical challenge category. Time-to-treatment will be summarized as mean (SD) within each stratum (e.g., none vs resolved vs unresolved, and by category) and compared across strata.	From enrolment to end of treatment at 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline tissue at risk for amputation (Hennepin Frostbite Score at-risk component)	Baseline tissue at risk will be quantified using the Hennepin Frostbite Score at-risk component, documented at initial assessment (before 1st treatment administration). Results will be summarised as score values (mean [SD]).	From enrolment to 1 week after treatment initiation
Overall digital salvage rate at 6 and 12 months (Hennepin Frostbite Score-defined digits at risk vs amputated) after treatment completion	At 6 and 12 months, the digital salvage rate will be calculated as the proportion of digits at risk that are not amputated, where "digits at risk" and "amputated" are determined using the Hennepin Frostbite Score methodology and follow-up documentation. Results will be reported as n/N and % with 95% confidence intervals, and may be compared with prespecified historical proportions from the literature (one-sample proportion testing as applicable).	From enrolment to 18 months after treatment completion
Number of participants undergoing any frostbite-related amputation by 6 months and by 12 months after end of treatment (clinical charts/operative notes & self reported)	Amputation status (any vs none) will be ascertained from clinical charts, operative notes and self reports at six and twelve months after treatment completion. Results will be reported as n (%) with 95% confidence intervals, and may be compared with pre-specified historical rates from the literature if feasible.	from enrollment to follow ups up to 18 months after discharge.
Number of joints salvaged per participant at 6 and 12 months (Hennepin Frostbite Score-based joint tissue at risk vs amputated)	At 6 and 12 months after treatment completion, the number of joints salvaged per participant will be determined from the Hennepin Frostbite Score tissue-at-risk mapping and documented final tissue loss/amputation level. Results will be summarized per participant (e.g., mean [SD] and/or distributional summaries) at each timepoint.	From enrolment to 18 months after discharge
Change from baseline in pain at follow-up (measured by Numeric Rating Scale (NRS) 0-10)	Pain intensity will be recorded using the Numeric Rating Scale (NRS) 0-10 as documented in clinical charts/notes at baseline (initial clinical assessment) and self reported at 6 months and 12 months follow-up. The outcome will be change from baseline in NRS score at each follow-up timepoint (follow-up minus baseline). Results will be summarised as mean (SD) at 6 and 12 months (and mean (SD) change), with within-person comparisons over time analysed using paired t-tests.	from enrolment to 18months after treatment completion
Change from baseline in upper-extremity function at 6 and 12 months (QuickDASH, self-reported)	Upper-extremity function will be assessed using the QuickDASH (11-item self-reported questionnaire about Disabilities of the Arm, Shoulder and Hand (DASH)) at baseline, 6 months, and 12 months. The outcome will be change from baseline in QuickDASH score at each follow-up timepoint (follow-up minus baseline). Results will be summarised as mean (SD) at 6 and 12 months (and mean (SD) change), with within-person comparisons over time analysed using paired t-tests (or pre-specified nonparametric alternatives if assumptions are not met). This assessment will only be undertaken in patients whit frostbites on the upper extremity.	From enrolment to 18months after treatment completion
Change from baseline in foot/ankle function at 6 and 12 months (FAAM-ADL, self-reported)	Foot/ankle function will be assessed using the Foot and Ankle Ability Measure (FAAM) - Activities of Daily Living (ADL) subscale, a self-reported questionnaire, at baseline, 6 months, and 12 months. The outcome will be change from baseline in FAAM-ADL score at each follow-up timepoint. Results will be summarised as mean (SD) at 6 and 12 months (and mean (SD) change), with within-person comparisons analysed using paired t-tests (or pre-specified nonparametric alternatives if assumptions are not met). This assessment will only be undertaken in patients with frostbites affecting the lower extremities.	From enrolment to 18 months after treatment completion

Collaborators and Investigators

• Sponsor: Institute of Mountain Emergency Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: February 20, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: iloprost
• Additional Relevant MeSH Terms: Cold Injury; Wounds and Injuries; Frostbite; Fatty Acids; Lipids; Biological Factors; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Autacoids; Inflammation Mediators; Iloprost
• Other Study ID Numbers: HAI-Frost

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.