Iloprost

證據等級: L5

預測適應症: 9 個

Note on scope: this evidence pack (TW-DB01088-multi) screened 9 candidate indications, not one. The TxGNN top-score candidate (rank 1, hypotrichosis) has zero supporting evidence and is not a credible lead. I've built the report around the strongest evidence-backed candidate (rank 3, PAH associated with congenital heart disease — L2, Proceed with Guardrails), and added a summary table of the other 8 candidates for completeness.

Iloprost: From Pulmonary Arterial Hypertension to Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

One-Sentence Summary

Iloprost is a synthetic prostacyclin (PGI2) analogue and IP-receptor agonist, internationally approved for WHO Group 1 pulmonary arterial hypertension (inhaled and intravenous formulations); it is not currently marketed in New Zealand. The TxGNN model, together with real-world evidence, supports its use in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease — a recognized WHO Group 1 subtype — with 1 clinical trial and 20 publications currently identified. This same evidence pack also flagged two other PAH subtypes (connective tissue disease–associated and HIV-associated PAH) at the same evidence tier, while several non-PAH predictions (e.g., hair-loss disorders) had no supporting evidence at all.

Quick Overview

Item	Content
Original Indication	Pulmonary Arterial Hypertension (WHO Group 1) — established international indication (inhaled/IV); no New Zealand–specific approved indication text on file
Predicted New Indication	Pulmonary Arterial Hypertension Associated with Congenital Heart Disease
TxGNN Prediction Score	99.32% (rank 5603)
Evidence Level	L2
New Zealand Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed, structured mechanism-of-action data was not retrieved from DrugBank for this candidate (data gap DG002). Based on information embedded in the evidence pack itself, iloprost is a synthetic prostacyclin (PGI2) analogue that acts as an IP-receptor agonist, producing pulmonary and systemic vasodilation and inhibiting platelet aggregation. It is already approved and used clinically for WHO Group 1 pulmonary arterial hypertension via inhaled (e.g., Ventavis) and intravenous (e.g., Ilomedin) formulations.

Pulmonary arterial hypertension associated with congenital heart disease (including Eisenmenger physiology) is classified within the same WHO Group 1 PAH umbrella as idiopathic PAH. The underlying pathophysiology — pulmonary vascular remodeling, elevated pulmonary vascular resistance, and endothelial dysfunction — is shared across Group 1 subtypes, which is why prostacyclin-pathway therapies are used as a class across this entire group.

Because iloprost's vasodilatory and antiplatelet mechanism targets the pathophysiology common to all Group 1 PAH subtypes rather than being specific to idiopathic disease, extending its use to the congenital-heart-disease subtype is a mechanistically direct, low-novelty extension rather than a speculative new mechanism — consistent with the L2/"Proceed with Guardrails" scoring assigned in this evidence pack.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01383083	N/A	Unknown	42	Safety, tolerability, and hemodynamic effects of iloprost in adult PAH related to congenital heart disease (Eisenmenger physiology); relevance graded A (directly targets this population), but phase is unlabeled and trial status is unverified

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28608969	2017	Cohort	Clin Exp Pharmacol Physiol	Iloprost's effect on endothelial biomarkers (NO, ET-1, ADMA, Gal-3, BNP, UA) in CHD-PAH patients
29426959	2018	Cohort	Pediatr Cardiol	Acute hemodynamic effects and safety of inhaled iloprost in children with simple CHD-associated PAH
24729548	2015	Cohort	Pediatr Pulmonol	Long-term effects of inhaled iloprost in children with pulmonary hypertension
30719004	2018	Cohort	Front Pharmacol	Cardiac MRI study showing acute iloprost inhalation improves right ventricular function in PAH
19436672	2009	Review	Vasc Health Risk Manag	Review of inhaled iloprost for pulmonary hypertension control in children
36010107	2022	Case Series	Children (Basel)	Long-term add-on sildenafil + bosentan + iloprost strategy in Eisenmenger syndrome (n=5)
25316472	2014	Case Report	Saudi Med J	Intensive inhaled iloprost + sildenafil resolved pericardial effusion in unrepaired VSD with severe PAH
27053694	2016	Consensus Statement	Heart	European expert consensus on hemodynamic assessment and vasoreactivity testing in pediatric pulmonary vascular disease
16919006	2006	Review	Eur J Clin Invest	Treatment options, including prostacyclin analogues, in children with PAH
17990138	2007	Registry	Swiss Med Wkly	Swiss national PAH registry — paediatric experience

New Zealand Market Information

Iloprost is not currently marketed in New Zealand — no Medsafe authorization records were found (0 licenses on file).

Other Candidate Indications Screened (This Evidence Pack)

Rank	Predicted Indication	TxGNN Score	Evidence Level	Decision
1	Hypotrichosis simplex of the scalp	99.45%	L5	Hold
2	Congenital hypotrichosis milia	99.33%	L5	Hold
4	Pulmonary arteriovenous malformation	99.31%	L4	Hold
5	PAH associated with connective tissue disease	99.21%	L2	Proceed with Guardrails
6	PAH associated with HIV infection	99.21%	L2	Proceed with Guardrails
7	PAH associated with chronic hemolytic anemia	99.21%	L4	Research Question
8	PAH associated with schistosomiasis	99.21%	L4	Research Question
9	Diffuse alopecia areata	99.10%	L5	Hold

Ranks 5 and 6 have comparable evidence strength to the featured indication and warrant the same guardrails; ranks 1, 2, 4, and 9 lack a plausible mechanistic or evidentiary basis and should not be pursued without new data.

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Iloprost's vasodilatory/antiplatelet mechanism is already validated across WHO Group 1 PAH, and CHD-associated PAH is supported by 20 publications plus one directly relevant (though status-unverified) clinical trial. However, the primary trial identified (NCT01383083) has unknown status and no confirmed completion outcome, and no MOA or formal safety-label data are on file for this drug.

To proceed, the following is needed:

Resolve data gap DG001 (TFDA/international package insert warnings and contraindications) — currently Blocking, and must be cleared before any S1 safety evaluation
Resolve data gap DG002 (formal DrugBank MOA record) to support the mechanistic rationale with structured data
Verify current status and outcome of NCT01383083
Since iloprost is not marketed in New Zealand, confirm regulatory pathway (e.g., new registration vs. named-patient/compassionate use) before any local development
Consider parallel evaluation of the two other L2 candidates (CTD-associated and HIV-associated PAH), which share the same class-level rationale
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.