Field Study on Intravenous Iloprost for Treatment of Severe Frostbite at High Altitude

Condition(s) studied

Investigational drug(s) / intervention(s)

Iloprost (Ilomedin, BAYQ6256): Begin Iloprost intravenous infusion as soon as feasible for all Grade 2-4 frostbite cases (optimally within 24-72 hours of injury, but it can be beneficial even if started later). Iloprost is a prostacyclin analogue vasodilator that improves blood flow and inhibits platelet aggregation, thereby counteracting frostbite's ischemic and thrombotic components. Key points for Iloprost administration: * Dosage and preparation: Iloprost is supplied in ampoules of 50mcg/0.5mL. Dilute 50 mcg into a 250mL bag of D5W (5% dextrose) to create a 0.2 mcg/mL solution. Iloprost infusion should be administered via a dedicated IV line using an infusion pump. * Infusion protocol: Start iloprost infusion at 10 mL/hour (which delivers 2 mcg/hour, assuming the 0.2 mcg/mL dilution). Every 30 minutes, increase infusion rate by 10 mL/hour, as tolerated, until the maximum rate appropriate for the patient's weight is reached (40-50 kg: up to 30 mL/hour; 51-74 kg: up to 40 mL/hour; ≥75 kg: up to 50 mL/hour.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Proportion of frostbite presentations with severe frostbite (Grade 3-4) at Everest ER — from enrolment to the end of treatment at 1 week
  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 (%)
• Proportion of eligible severe frostbite patients who complete ≥1 field iloprost treatment round — From enrolment to 1 week after beginning of treatment
  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 (%)
• Time from thawing to initiation of iloprost treatment under field conditions — From enrolment to the end of treatment at day 1
  Unit/format: time (hours or minutes)
• Proportion of iloprost-treated patients with mild adverse effects during/after ≥1 treatment round in the field setting — From enrollment to the end of treatment at 1 week
  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.
• Proportion of iloprost-treated patients with severe adverse effects during/after ≥1 treatment round in the field — From enrolment to the end of treatment at 1 week
  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
• Proportion of patients discontinuing field iloprost treatment (overall) and documented reasons for discontinuation — From enrolment to end of treatment at 1 week
  Proportion of discontinued field treatments in relation to all initiated field treatments. Unit/format: proportion (%) + categorical reason counts
• Proportion of iloprost treatment discontinuations attributable to adverse effects in the field — From enrolment to end of treatment at 1 week
  Unit/format: proportion (%) Number of treatments discontinued due to adverse reactions in relation to all treatments discontinued (both in the field)
• Qualitative description of logistical constraints and solutions from field notes and staff reports — From enrolment to end of treatment at 1 week
  Notes and reports will be analysed using a thematic analysis approach to categorise logistical challenges. Reported as: themes/categories with illustrative summaries (qualitative)
• Frequency of logistical challenges during field iloprost implementation — from enrolment to end of treatment at 1 week
  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)
• Proportion of logistical challenges resolved during the study period — from enrolment to end of treatment at week 1
  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.
• 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 — From enrolment to end of treatment at 1 week
  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.

Trial sites (1)

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