Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial

Abstract

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups—between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060–0.141) and 0.099 L (95% BCI, 0.048–0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

<p>An Integrative Approach of the Fissure Completeness Score and Chartis Assessment in Endobronchial Valve Treatment for Emphysema</p>

“…Two recently published randomized controlled trials treated patients based on FCS >90% alone, the EMPROVE and the REACH trial. 19,20 They showed an FEV1 improvement of >15% in 37.2% and 41% of the patients, an RV reduction of 402 and 420 mL and a target lobe volume reduction of >350 mL reduction in 74.5 and 66.1%, respectively. However, the mean FCS in the REACH trial was 97.8% and the mean FCS of the EMPROVE trial is not known.…”

“…12,13 Although Chartis measurement is clinical practice in many clinics, there are recent studies that advocate the use of the fissure cut-off score of 90% only. 19,20 However, more accurate selection of responder patients prevents unnecessary procedures, non-beneficial treatments and extra costs in patients with collateral ventilation. Therefore, we performed a study to correlate the FCS to the Chartis assessment.…”

<p>Patient Selection for Bronchoscopic Lung Volume Reduction</p>

“…The proportion of visually intact fissures was in line with previously published data on this topic, and also in agreement with the latest clinical trials investigating EBV and intrabronchial valves, in which the left upper and left lower lobe were selected for treatment in more than 75% of cases. 11,32,33 This study has several limitations: first of all, our population is representative of the group of patients referred to a BLVR center but not of the total population of patients with severe emphysema, and can therefore not serve to accurately assess the proportion of eligible patients for BLVR in the total population of patients with emphysema. Second, inherent to the retrospective nature of this study, we had to rely on the quality of the referral documentation from other hospitals.…”

Lung Volume Reduction in Pulmonary Emphysema

“…EMPROVE in 2019 was a U.S. multicenter RCT of 172 patients with severe heterogeneous emphysema (!10% difference between target and ipsilateral lobes), intact interlobar fissures (!90%), and hyperinflation comparing the SVS (n ¼ 113) to SoC (n ¼ 59). 47 The primary efficacy endpoint, the difference in the groups' FEV1 changes at 6 months, was statistically significant favoring the treatment arm, 0.101 L (95% CI: 0.060-0.141), and a responder rate for FEV1 !15 of 36.8% (10.0% SoC). This was accompanied by a mean TLVR of 974 mL (MCID of À350 mL was achieved in 75% of treated patients), reduction in RV of 402 mL and in SGRQ of À8.1 points.…”