Calfactant
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Calfactant
- Calfactant: From Neonatal Respiratory Distress Syndrome to Adult Acute Respiratory Distress Syndrome
Calfactant: From Neonatal Respiratory Distress Syndrome to Adult Acute Respiratory Distress Syndrome
One-Sentence Summary
Calfactant is a natural calf lung surfactant, originally used for neonatal respiratory distress syndrome and acute respiratory distress syndrome (ARDS). The TxGNN model predicts it may be effective for adult acute respiratory distress syndrome, with 1 clinical trial (a terminated Phase 3 study) and 5 publications currently bearing on this question. Because ARDS is already a listed original indication, this is not a true repurposing candidate. The open question is whether adults benefit.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Neonatal respiratory distress syndrome; acute respiratory distress syndrome (from the knowledge graph, as no approved indication text is available in the Singapore licence record) |
| Predicted New Indication | Adult acute respiratory distress syndrome |
| TxGNN Prediction Score | 95.78% |
| Evidence Level | L1 (as scored in the compiled data; see the caveat below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Evidence level caveat: The data compiled for this report assign L1. However, the only adult Phase 3 trial was terminated, not completed, so it does not meet the strict L1 definition (two or more completed Phase 3 RCTs). The evidence is better read as direct but non-confirmatory.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. The surfactant replacement mechanism is well established, however. Calfactant is a calf lung surfactant extract containing phospholipids and surfactant proteins B and C. In ARDS, endogenous surfactant is inactivated and depleted. This causes alveolar collapse, reduced lung compliance and impaired oxygenation. Replacing surfactant is therefore biologically plausible.
The original indications already include neonatal respiratory distress syndrome and ARDS. The real question is whether the benefit seen in neonates and children extends to adults. Earlier trials of several surfactant preparations in adults with acute lung injury were unsuccessful. Calfactant contains a high level of surfactant protein B, which was the rationale for testing it again in adults.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00682500 | Phase 3 | Terminated | 332 | Intratracheal calfactant in adults and children with direct ARDS or acute lung injury, started within 48 hours of mechanical ventilation. The aim was to reduce mortality and shorten respiratory failure. The trial ran from 2008-05 to 2011-02. The reason for termination should be verified in the registry record and publication, and the result should not be treated as confirmation. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25855884 | 2015 | RCT | Chest | Adult Calfactant in ARDS trial: multicentre, randomised, masked study of calfactant in adults and children with ALI/ARDS, motivated by positive paediatric results and the potential of SP-B-containing surfactants |
| 15671432 | 2005 | RCT | JAMA | Randomised trial of calfactant in paediatric acute lung injury. Preliminary paediatric studies suggested benefit, while earlier adult surfactant trials had failed |
| 23925143 | 2013 | Cohort (post hoc analysis) | Pediatric Critical Care Medicine | Post hoc analysis of the paediatric calfactant ARDS trial examining the relationship between fluid balance and in-hospital outcomes |
| 21048239 | 2010 | Review | Indian Pediatrics | Overview of paediatric ARDS, its causes, mortality risk and supportive therapies |
| 17198050 | 2007 | Review | Current Opinion in Critical Care | Paediatric mechanical ventilation, including timing of intubation, ventilatory strategies and weaning |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14333P | Infasurf Intratracheal Suspension 35mg/mL | Suspension, sterile | Not specified in the licence record |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The surfactant replacement mechanism is plausible and the drug is already marketed in Singapore. However, the only adult Phase 3 trial was terminated, and the other supporting literature is mainly paediatric or review material. There is no confirmed adult efficacy. The other nine predicted indications, such as neurolymphomatosis, plasmacytoma and myasthenia gravis, have no plausible mechanism and no trials or literature, and are likely knowledge-graph artifacts. Pulmonary edema has only a partial rationale that overlaps with ARDS.
To proceed, the following is needed:
- The reason for termination of NCT00682500 and its published results, including the mortality and ventilation outcomes in adults
- The Singapore package insert, covering approved indications, warnings and contraindications
- Mechanism of action data from DrugBank
- A subgroup analysis of adults versus children in the Adult Calfactant in ARDS trial
- Confirmation that the Singapore product's intratracheal route suits the intended adult ventilated population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.