Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) Study (RENEW)

Multicenter, randomized, assessor-blinded controlled study of safety and effectiveness of the PneumRx, Inc. RePneu Lung Volume Reduction Coil (RePneu LVRC) System

Study Overview

• Status: Terminated
• Conditions: Emphysema
• Intervention / Treatment: Device: RePneu Lung Volume Reduction Coil System

Detailed Description

This will be a prospective, multicenter, randomized, assessor-blinded, controlled study comparing outcomes between the LVRC and Control Groups. Subjects will be block randomized in an LVRC (Treatment) to Control ratio of 1:1. The randomization will be stratified by homogeneous versus heterogeneous emphysema, to support a balance of patients with differing heterogeneity in both the LVRC and Control Groups.

• Study Type: Interventional
• Enrollment (Actual): 315
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)
• France
  • Nice, France, CS 51069
    • Centre Hospitalier Universitaire de Nice
  • Reims, France, 51092
    • CHU de Reims - Hôpital Maison Blanche
• Germany
  • Heidelberg, Germany, D-69126
    • Thoraxklinik University of Heidelberg
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital & Chelsea Westminster
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Lung Health Center
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital/Palo Alto Medical Foundation
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine - Yale New Haven Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital and Health Center
    • Peoria, Illinois, United States, 61606
      • Illinois Lung and Critical Care Institute
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Pulmonary and Critical Care Associates of Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple
    • Pittsburgh, Pennsylvania, United States, 15213
      • Emphysema COPD Research Center, University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425-6300
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Pulmonary, Critical Care & Sleep Medicine Consultants,PCCS/St. Luke's Episcopal Hospital
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Sciences Center at San Antonio
  • Washington
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine & Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is greater than or equal to 35 yrs of age
• CT Scan indicates bilateral emphysema, as determined by the Core Radiology Lab using the criteria presented in the "CT Scoring Plan for Core Radiology Lab"
• Subject has post-bronchodilator FEV1 less than or equal to 45% predicted
• Subject has Total Lung Capacity >100% predicted
• Subject has residual volume (RV) greater than or equal to 175% predicted
• Subject has marked dyspnea greater than or equal to 2 on mMRC scale of 0-4
• Subject has stopped smoking for at least 8 weeks prior to entering the study as confirmed by a Cotinine test or other appropriate diagnostic test.
• Subject has completed a pulmonary rehabilitation program within 6 mos prior to treatment and/or is regularly performing maintenance respiratory rehabilitation if initial supervised therapy occurred more than 6 mos prior to baseline testing.
• Subject has received Pneumococcal and Influenza vaccinations consistent with local recommendations and/or policy.
• Subject (and legal guardian, if applicable) has read, understood, and signed the Informed Consent form.

Exclusion Criteria:

• Subject has severe homogeneous emphysema determined by Core Radiology Lab.
• Subject has co-morbidities that may significantly reduce subject's ability to improve exercise capacity (e.g., severe arthritis, planned knee surgery) or baseline limitation on 6MWT is not due to dyspnea.
• Subject has a change in FEV1 of greater than 20% (or, for subjects with pre-bronchodilator FEV1 below 1L, a change of greater than 200mL) post-bronchodilator unless investigator can confirm by other means that subject does not have asthma.
• Subject has DLCO of less than 20% of predicted.
• Subject has severe gas exchange abnormalities, PaCO2 of greater than 55mm Hg; PaO2 of less than 45 mm Hg on room air (high altitude criterion: PaO2 of less than 30mm Hg).
• Subject has a history of recurrent clinically significant respiratory infections, defined as 3 hospitalizations for respiratory infection during the year prior to enrollment.
• Subject as severe pulmonary hypertension defined by right ventricular systolic pressure of greater than 50mm Hg via right heart catheterization and/or echocardiogram
• Subject has an inability to walk >140m (150 yd) in 6 minutes
• Subject has evidence of other severe disease (such as but not limited to lung cancer or renal failure), which in the judgment of the investigator may compromise survival of the subject for the duration of the study.
• Subject is pregnant or lactating, or plans to become pregnant within the study timeframe.
• Subject has an inability to tolerate bronchoscopy under moderate sedation or general anesthesia.
• Subject has clinically significant bronchiectasis.
• Subject has giant bullae >1/3 lung volume
• Subject has had previous LVR surgery, lung transplantation, lobectomy or LVR devices or other device to treat COPD in either lung.
• Subject has been involved in pulmonary drug or device studies within 30 days prior to this study.
• Subject is taking >20mg prednisone (or equivalent dose of a similar steroid) daily.
• Subject requires high level chronic immunomodulatory therapy to treat a moderate to severe chronic inflammatory autoimmune disorder.
• Subject is on an antiplatelet agent (such as Plavix) or anticoagulant therapy (such as Heparin or Coumadin) which cannot be stopped for 7 days prior to the procedure.
• Subject has any other disease, condition(s) or habit(s) that would interfere with completion of study and follow up assessments, would increase risks of bronchoscopy or assessments, or in the judgment of the investigator would potentially interfere with compliance to this study or would adversely affect study outcomes.
• Subject has a sensitivity or allergy to nitinol (nickel-titanium) or its constituent metals.
• Subject has a known sensitivity to drugs required to perform bronchoscopy.
• Subject has been diagnosed with alpha-1 antitrypsin deficiency (AATD).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RePneu Lung Volume Reduction Coil System; The RePneu Lung Volume Reduction Coil System is an implantable device, delivered through a fiber-optic bronchoscope. This is a two part system that consists of 1) sterile Nitinol Coils and 2) a sterile, disposable, single-use (single-patient) Delivery System consisting of a Guidewire, Catheter, Cartridge, and Forceps.	Device: RePneu Lung Volume Reduction Coil System; The LVRC group will undergo two bronchoscopic sessions under general or moderate sedation. During the procedure, subjects will be treated with Coils according to the Instructions for Use.
No Intervention: Control arm is standard medical care; The Control Group will not undergo any bronchoscopies for Coil placement and will not receive prophylactic antibiotics or steroids before and after 'treatment' or chest x-rays in connection with the 'treatment' visits. The frequency of visits to the Study Doctor or designee will be similar to the LVRC Group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meters: 6 Minute Walk Test - Change From Baseline to 12 Months Follow up	mean absolute change from baseline at 12 months in the 6 Minute Walk Test comparing test and control groups (median if skewed)	baseline through 12 months follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in FEV1 From Baseline to 12 Months	Mean percent change in FEV1(Forced Expiratory Volume in 1 second) at 12 months (median if skewed)	BL to 12 months
St. George's Respiratory Questionnaire (SGRQ) Mean Absolute Change From Baseline to 12 Months	mean absolute difference in SGRQ results comparing BL to 12 months, LVRC vs. Control, score is on a scale from 0 to 100, negative change will be a better outcome.	BL to 12 months
6MWT Responder Analysis	6MWT Responder Analysis: Responder is defined as those with an improvement of greater than or equal to 25 meters	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SGRQ Responder Analysis	SGRQ Responder Analysis: Responder defined as those with an improvement greater than or equal to 4 points	12 months
Residual Volume (RV) Mean Absolute Difference in RV From Baseline to 12 Months	Mean absolute difference in RV results measured using plethysmography, comparing BL to 12 months, LVRC vs. Control	12 months
RV/TLC Mean Absolute Difference From Baseline to 12 Months	Mean absolute difference in RV/TLC (residual volume/total lung capacity - a measure done during lung function testing where residual volume is air left over in lung after completely breathing out and total lung capacity is how much air the lung can breathe in) results measured using plethysmography, comparing BL to 12 months, LVRC vs. Control	12 months

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Collaborators: PneumRx, Inc.

Publications and helpful links

General Publications

• Hartman JE, Shah PL, Sciurba F, Herth FJF, Slebos DJ; RENEW Study Group. Endobronchial coils for emphysema: Dual mechanism of action on lobar residual volume reduction. Respirology. 2020 Nov;25(11):1160-1166. doi: 10.1111/resp.13816. Epub 2020 Apr 8.
• Slebos DJ, Cicenia J, Sciurba FC, Criner GJ, Hartman JE, Garner J, Deslee G, Delage A, Jantz M, Marquette CH, Strange C, Hatipoglu U, Mehta AC, LaPrad AS, Schmid-Bindert G, Herth FJF, Shah PL; RENEW Study Group. Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema. Chest. 2019 May;155(5):928-937. doi: 10.1016/j.chest.2019.02.012. Epub 2019 Feb 21.
• Sciurba FC, Criner GJ, Strange C, Shah PL, Michaud G, Connolly TA, Deslee G, Tillis WP, Delage A, Marquette CH, Krishna G, Kalhan R, Ferguson JS, Jantz M, Maldonado F, McKenna R, Majid A, Rai N, Gay S, Dransfield MT, Angel L, Maxfield R, Herth FJ, Wahidi MM, Mehta A, Slebos DJ; RENEW Study Research Group. Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial. JAMA. 2016 May 24-31;315(20):2178-89. doi: 10.1001/jama.2016.6261.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): July 26, 2019

Study Registration Dates

• First Submitted: May 26, 2012
• First Submitted That Met QC Criteria: May 30, 2012
• First Posted (Estimate): May 31, 2012

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: COPD; RePneu
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: CLN0009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided