Iloprost

證據等級: L5

預測適應症: 10 個

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

Note on candidate selection: This evidence pack (TW-DB01088-multi) scored 10 candidate indications. The two highest-scoring predictions (hypotrichosis simplex of the scalp; congenital hypotrichosis milia) are explicitly flagged in the pack’s own rationale as likely knowledge-graph noise (zero trials, zero literature, no mechanistic plausibility). This report instead focuses on the highest-scoring clinically plausible candidate — PAH associated with congenital heart disease — and summarises four related PAH-subtype predictions below it. Diseases judged as noise are listed at the end for completeness.

One-Sentence Summary

Iloprost is a prostacyclin (PGI2) analogue; a formal record of its original approved indication is not available in this evidence pack, but its established pharmacological role — described consistently throughout the evidence — is pulmonary vasodilation in pulmonary arterial hypertension (PAH). The TxGNN model predicts efficacy in PAH associated with congenital heart disease, a recognised PAH subtype, with 1 clinical trial and 20 publications currently identified. Four related PAH-subtype predictions (connective tissue disease, HIV infection, schistosomiasis, chronic haemolytic anaemia) carry similar or lower evidence support.

Quick Overview

Item	Content
Original Indication	Not formally recorded in this evidence pack (data gap); established use elsewhere is pulmonary arterial hypertension, per rationale notes across multiple predicted indications
Predicted New Indication	Pulmonary arterial hypertension associated with congenital heart disease
TxGNN Prediction Score	99.32%
Evidence Level	L2
Australia Market Status	Not currently marketed (未上市)
Number of ARTG Entries	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is marked as a data gap in the structured drug record. However, the evidence pack’s repurposing rationale consistently describes Iloprost as a prostacyclin (PGI2) analogue that activates the IP receptor, producing pulmonary vasodilation and inhibiting platelet aggregation — the standard mechanistic basis for PAH (WHO Group 1) therapy.

PAH associated with congenital heart disease (including Eisenmenger physiology) is classified as a clinical subtype within the same WHO Group 1 PAH family as idiopathic PAH. The rationale explicitly frames this as an extension within an existing indication class rather than a novel mechanistic hypothesis — the underlying pulmonary vascular pathology (vasoconstriction, remodelling, elevated pulmonary vascular resistance) is shared across subtypes, which is why prostacyclin analogues are used across the WHO Group 1 spectrum in practice.

This mechanistic continuity also explains why several other WHO Group 1 subtypes appear as related high-scoring predictions in this pack (connective tissue disease-associated, HIV-associated, schistosomiasis-associated, and chronic haemolytic anaemia-associated PAH) — they are pathophysiological variants of the same disease category rather than unrelated indications.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT01383083	N/A	Unknown	42	Assessed safety, tolerability, and haemodynamic effects of Iloprost in adults with PAH related to congenital heart disease (Eisenmenger physiology); addresses a rare, complex population with limited prior treatment evidence.

No ANZCTR-registered trials were identified for this indication.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28608969	2017	Cohort/Biomarker study	Clin Exp Pharmacol Physiol	Investigated endothelial biomarkers (NO, ET-1, ADMA, Gal-3, BNP, UA) in CHD-PAH and the effect of Iloprost on their regulation.
29426959	2018	Interventional acute-response study (paediatric)	Pediatr Cardiol	Evaluated safety and acute haemodynamic effects of inhaled Iloprost during cardiac catheterisation in children with PAH-CHD.
27053694	2016	Cohort / expert consensus	Heart	European consensus on haemodynamic assessment and acute pulmonary vasoreactivity testing in paediatric pulmonary vascular disease, including CHD-associated PAH.
19436672	2009	Review	Vasc Health Risk Manag	Reviews inhaled Iloprost use for pulmonary artery hypertension control in children, including CHD-associated cases.
16919006	2006	Review	Eur J Clin Invest	Overview of treatment options in paediatric PAH, noting congenital heart disease as a leading cause.
25316472	2014	Case report	Saudi Med J	Complete resolution of chronic pericardial effusion with intensive inhaled Iloprost in an adult with unrepaired VSD and severe PAH.
15929625	2005	Review	Rev Port Cardiol	Discusses new PAH drug classes, including prostacyclin analogues, applied to Eisenmenger syndrome and other CHD-related PAH.
30719004	2018	Prospective cohort (cardiac MRI)	Front Pharmacol	Acute inhaled Iloprost improved right ventricular function in PAH patients on cardiac magnetic resonance imaging.
24729548	2015	Retrospective study	Pediatr Pulmonol	Long-term effects of inhaled Iloprost analysed in children with pulmonary hypertension, a population overlapping with CHD-PAH.
21852894	2009	Review	Prog Pediatr Cardiol	Discusses paediatric PAH aetiologies beyond congenital heart disease, providing differential context for CHD-PAH management.

Australia Market Information

Iloprost has no ARTG-registered products in Australia (0 entries on record; market status: not currently marketed).

The following WHO Group 1 PAH subtypes were also predicted with similar TxGNN scores and share the same mechanistic rationale as the lead candidate above:

Disease	TxGNN Score	Evidence Level	Recommendation	Evidence Summary
PAH associated with connective tissue disease	99.21%	L3	Proceed with Guardrails	0 trials; 20 publications (mostly reviews/cohorts), including long-term IV Iloprost outcomes data
PAH associated with HIV infection	99.21%	L2	Proceed with Guardrails	1 completed Phase 3 trial (NCT00709956, PROWESS-15, n=64; HIV-PAH was a sub-population, not the sole enrolment criterion); 4 publications
Pulmonary arteriovenous malformation	99.31%	L4	Research Question	0 trials; 1 publication; structural (not vasoconstrictive) pathology — mechanistic link is weak
PAH associated with schistosomiasis	99.21%	L4	Research Question	0 trials; 1 publication (not schistosomiasis-specific)

Excluded as likely model noise (no supporting evidence, Hold recommendation): hypotrichosis simplex of the scalp, congenital hypotrichosis milia, PAH associated with chronic haemolytic anaemia, diffuse alopecia areata, alopecia.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Iloprost’s prostacyclin mechanism is well established for PAH broadly, and PAH-CHD is a recognised subtype rather than a novel indication hypothesis — but the sole disease-specific trial identified has unknown status and unspecified phase, and Iloprost is not currently registered in Australia, so clinical use here would be off-label/unregistered pending further evaluation.

To proceed, the following is needed:

TGA/PI-equivalent safety, warnings, and contraindication data (currently a blocking data gap)
Formal mechanism-of-action and original-indication documentation for the drug record
Confirmation of trial phase/status for NCT01383083, or identification of more definitive PAH-CHD trials
ARTG registration pathway assessment, given the drug is not currently marketed in Australia
Disclaimer

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