| Summary: | Objective: VOLUME is a randomized, open-label, post-approval pragmatic trial aiming to evaluate long-term pulmonary and cardiovascular safety of Exubera® (EXU; insulin human [rDNA origin] Inhalation Powder) in routine clinical practice. The primary study objective is to compare risk of persistent decline in forced expiratory volume in 1 second (FEV1) among patients treated with and without EXU. Research design and methods: Patients eligible to take EXU per approved local label were randomized to EXU or routine care and followed per usual care, with scheduled FEV1 tests at baseline, 6 months, and yearly.Randomization halted in October 2007 after Pfizer announced it would stop marketing EXU due to low sales. EXU patients were subsequently transitioned to usual care and all patients were followed for 6 additional months. Results: Although there was insufficient power to evaluate the primary endpoint (37% of the planned 5,300 were randomized), the study provided important descriptive information.Per the primary endpoint definition, more EXU group patients (n = 8) experienced a persistent decline in FEV1 (n = 0 in usual care). Using a broader, clinically relevant pre-specified supplementary definition of persistent decline, similar numbers were observed in the EXU (n = 27) and usual care (n = 24) groups. Slightly more pulmonary and allergic serious adverse event composite endpoints were seen in the EXU group. There were no consistent treatment group differences in the cardiovascular composite endpoint, all-cause mortality, or glycemic control. Conclusions: Clinically important declines in lung function that persisted more than 60 days were uncommon and of similar frequency in Exubera and usual care. Clinicaltrials.gov: NCT00359801.
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