The science of PAH marches on: the SAPPHIRE trial

As we know, pulmonary arterial hypertension patients' lungs don't make enough nitric oxide, which is a vasodilator. But what if patients were given infusions of cells that were altered to produce blood vessel lining cells that would produce more nitric oxide in the lungs? Would it be a safe and effective treatment? The SAPPHIRE trial intended to find out.

Participants randomly received either a placebo or an infusion of cells once a month for four months for a total of 80 million cells. Unfortunately, because of COVID-19, the trial was interrupted when only twelve participants were enrolled. Five had received placebos and seven had received cell infusions over the first 6 months.

A trial with this few participants can't give us statistically reliable results, but it does move science forward nonetheless: It can suggest—at relatively low cost—whether a new treatment might have any benefit or if it might cause unexpected side effects. This can be evidence to support the need for a larger follow-up trial.

In SAPPHIRE, although they didn't seem to have improved pulmonary hemodynamics, the cell group of participants did seem to experience other changes that might have increased their exercise tolerance. SAPPHIRE also suggested that participants who had received cells improved their 6-minute walk distance and kept the improvement for the next six months. Still, the size of the improvement wasn't in itself large enough to justify a larger trial at the moment. The results confirmed that cell infusions of this type were safe, tolerable, and a feasible treatment.

All these results provide insights for the design of future trials using this type of therapy.

The full journal article is online in the Journal of Heart and Lung Transplantation.