Early phase clinical trials in pulmonary hypertension: how small is big enough?

In this issue of Thorax , Czepiel et al report the results of a double-blind randomised controlled trial of an oral agent, hymecromone, in patients with pulmonary hypertension (PH).1 The authors provide a sound biological rationale as to why hyaluronan, a constituent of the extracellular matrix, may have an important role in vascular biology. The agent subjected to study is hymecromone, an inhibitor of hyaluronan, which is approved in Europe and Asia for the treatment of biliary dyskinesia. There is certainly attraction in repurposing an approved agent, with a known track record of safety for potential use in a relatively rare disease state. This small single-centre trial included patients with both group 1 pulmonary arterial hypertension (PAH) and PH associated with interstitial lung disease (ILD-PH). The subgroups, therefore, were very small with five patients receiving active drug and three assigned to placebo in each of the two groups. While the inclusion of group 1 and group 3 patients together in one trial can cloud the results, …