PARIS – Apatients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.
Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according tochair of the thoracic medicine department at Temple University, Philadelphia.
In this randomized controlled trial, called, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.
“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.
High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.
When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV1) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.
Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.
Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.
At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.
A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV1, and dyspnea, as measured with the, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the . At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.
According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.
The endobronchial values “provide statistically and clinically meaningful improvements in FEV1, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.
On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal, also led by Dr. Criner and published earlier this year ( ). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.
Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.