Iloprost
| 證據等級: L5 | 預測適應症: 9 個 |
目錄
Iloprost: From Pulmonary Arterial Hypertension to PAH Associated with HIV Infection
One-Sentence Summary
Iloprost is a synthetic prostacyclin (PGI2) analog established for treatment of pulmonary arterial hypertension (PAH), acting via IP-receptor-mediated vasodilation and antiplatelet/antiproliferative effects. The TxGNN model predicts it may be effective for Pulmonary Arterial Hypertension Associated with HIV Infection, a specific etiological subtype of PAH, supported by 1 completed Phase 3 randomized controlled trial and 4 supporting publications.
Note: This evidence pack scored 9 candidate indications for iloprost, most within the broader PAH disease family (congenital heart disease-PAH, connective tissue disease-PAH, HIV-PAH, schistosomiasis-PAH, hemolytic anemia-PAH) plus two unrelated hair-disorder predictions with no supporting evidence. Of these, the HIV-PAH indication carries by far the strongest evidence (L1, Phase 3 RCT) and is the subject of this report.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available as a structured field in this evidence pack (data gap); mechanistically, iloprost is an established PGI2 analog used for pulmonary arterial hypertension (per repurposing rationale notes in the source data) |
| Predicted New Indication | Pulmonary Arterial Hypertension Associated with HIV Infection |
| TxGNN Prediction Score | 99.21% |
| Evidence Level | L1 |
| Germany Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed original-indication and mechanism-of-action data are not available as structured fields (flagged as data gaps DG001/DG002 in this evidence pack). Based on the mechanistic notes embedded in the evidence pack, iloprost is a synthetic prostacyclin (PGI2) analog that activates the IP receptor, producing pulmonary vascular smooth-muscle relaxation, inhibition of platelet aggregation, and suppression of smooth-muscle proliferation — the core pharmacologic pathway underlying PAH treatment.
HIV-associated PAH shares the same downstream pathology (pulmonary vascular remodeling and endothelial dysfunction) as other PAH etiologies, even though the upstream trigger (HIV-related endothelial injury) differs. Because iloprost's therapeutic effect operates on the shared vascular remodeling pathway rather than on the disease-specific trigger, this represents an on-class, label-adjacent expansion rather than a mechanistically novel repurposing hypothesis — analogous to the established use of another prostacyclin analog, epoprostenol, in HIV-PAH.
This is further supported by the fact that a completed Phase 3, double-blind, randomized, placebo-controlled, crossover trial (PROWESS 15) explicitly enrolled HIV-associated PAH patients alongside idiopathic/familial PAH patients, indicating this population is already considered part of the standard iloprost/prostanoid treatment paradigm in clinical practice.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00709956 | Phase 3 | Completed | 64 | Double-blind, randomized, placebo-controlled crossover study of single-dose inhaled Iloprost Power 15 on exercise capacity in symptomatic PAH patients, including those with HIV-associated PAH, NYHA class II–IV, either treatment-naive or on stable background bosentan/ambrisentan/sildenafil |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17195895 | 2006 | Review | The Mount Sinai Journal of Medicine | Overview of HIV-related pulmonary hypertension; estimated incidence ~0.5% of HIV-infected individuals, pathogenesis still unclear |
| 14720012 | 2003 | Review | American Journal of Respiratory Medicine | Reviews prostanoid therapy across PAH etiologies, including HIV infection, noting shared obstructive pulmonary microvascular pathology |
| 31090367 | 2019 | Cohort (Registry) | Terapevticheskii Arkhiv | Six-year National Registry analysis of PAH prevalence, clinical course, therapy, and mortality |
| 18260882 | 2007 | Review | Kardiologiia | Reviews controlled trials of prostacyclin and synthetic analogues across PAH subtypes including HIV infection |
Germany Market Information
No marketing authorizations were found for iloprost in the current dataset (0 authorizations, market status: not marketed).
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 RCT directly enrolled HIV-associated PAH patients, and the mechanistic rationale is an on-class, label-adjacent extension of iloprost's established PGI2 pathway rather than a novel mechanism — this is the strongest-evidence candidate among the nine indications scored in this pack (L1/S3, versus L2–L5 for the others).
To proceed, the following is needed:
- Resolve blocking data gap DG001: TFDA/BfArM package insert warnings and contraindications, required before any S1 safety assessment can proceed
- Resolve high-priority data gap DG002: formal DrugBank MOA confirmation
- Structured original-indication data (currently absent from the drug record)
- HIV-antiretroviral drug–drug interaction data, given this population's near-universal concomitant ART use
- A German market-entry/regulatory pathway assessment, since iloprost currently has zero marketing authorizations on file
- Subgroup-level efficacy/safety data specific to the HIV-PAH arm of NCT00709956, rather than the pooled PAH population result
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.