The VITAL Trail was a single arm open-label study evaluating isavuconazole for treatment of mucormycosis, published in Lancet ID This was discussed at Journal club on May 23, 2016, presented by our fellow Palash Samanta.  The aim of the study was to evaluate patients with probable or proven mucormycosis treated either primarily or secondarily with isavuconaozle (as new anti-fungal with anti-mucor activity).  Because this is a rare disease with significant mortality, and the standard of care, along with surgical control is amphotericin  B (lipid formulation), a control arm was not included. Instead, the compared cases to a rare-fungal disease registry (FungiScope) using matching methodology.

The investigators enrolled 21 patients treated primarily with isavuconazole, along with 11 treated for refractory disease and 5 initiated on isavuconazole for intolerance to primary therapy.  The majority of patients had a hematologic malignancy as their underlying illness. They evaluated at 42 and 84 days of therapy.

While very few patients had a complete response and a minority had either complete or partial response, the mortality rate at 42 days (33%) did not differ statistically from that of the controls (39%).  However, some of the controls were on deoxycholate amphotericin B, and the patients were matched based on surgical intervention and hematologic malignancy status, which are large predictors of mortality.

While the adverse event profile of isavuconazole was favorable in this study, the journal club participants were not convinced by this data that isavuconazole should replace liposomal amphotericin B as primary therapy in mucormycosis.  Data on therapeutic drug monitoring are still lacking, and the sample size in the study was very small.  Where this drug fits vis-a-vis posaconazole in the “step down” regimen for mucormycosis, following initial ampho B therapy remains to be seen.

Reference:

Marty FM et al Lancet Infect Dis. 2016 Mar 8

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