ELEVATE: Study of PneumRx Endobronchial Coil System in Treatment of Subjects With Severe Emphysema

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03360396
• Collaborator: PneumRx, Inc. (Industry)
• Enrollment: 120
• Locations: 19
• Arms: 2
• Anticipated Duration (Months): 58.8
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will look at outcomes between Endobronchial Coil Treatment and Control groups in patients with severe heterogeneous and or homogeneous emphysema.

Condition or Disease	Intervention/Treatment	Phase
Emphysema	Device: Endobronchial Coils	N/A

Detailed Description

This will be a prospective, multicenter, randomized, controlled study comparing outcomes between the Endobronchial Coil and Control Groups. Subjects will be block randomized in a Treatment to Control ratio of 2:1. The randomization will be stratified by site and homogeneous versus heterogeneous emphysema, to support a balance of patients with differing heterogeneity in both the Treatment and Control Groups

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Study of PneumRx Endobronchial Coil System Versus Standard-of-Care Medical Management in the Treatment of Subjects With Severe Emphysema
• Actual Study Start Date: May 7, 2018
• Actual Primary Completion Date: Feb 26, 2020
• Anticipated Study Completion Date: Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Endobronchial Coils Treatment with PneumRx Endobronchial Coil System	Device: Endobronchial Coils; Endobronchial Coil implants
No Intervention: Control Medically-managed control group

Outcome Measures

Primary Outcome Measures

1. Percent Change in FEV1 at 6 Months [6 months]

   Percent change in FEV1

2. Absolute Change in SGRQ Score at 6 Months [6 months]

   Change in SGRQ score - St. George Respiratory Questionnaire from 0 to 100, higher score indicating more limitations (worse), increase in score indicating worse outcome, decrease in score indicating improvement

Other Outcome Measures

1. Efficacy Analyses Post Primary Endpoint [12 and 36 months]

   Descriptive statistics will summarize effectiveness endpoints at 12 and 36 months for all coil treated subjects in France.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Read, understood and signed the Informed Consent form

• Meets indications for use per the IFU

• Bilateral heterogeneous and/or homogeneous emphysema

• Post bronchodilator 15% predicted ≤ Forced Expiratory Volume in 1 second (FEV1) ≤ 45% predicted

• Post bronchodilator Residual Volume (RV) ≥ 200% predicted

• Post bronchodilator Total Lung Capacity (TLC) >100% pred.

• Post bronchodilator RV/TLC > 55%

• Dyspnea related to hyperinflation scored ≥ 2 on modified Medical Research Council (mMRC) dyspnea scale despite optimal medical management

• Receiving optimal drug therapy and medical management according to clinical practice.

• Performing regular physical activity, at least 2 times per week

• Stopped smoking as confirmed by carboxyhemoglobin (CoHB)

• 100m ≤ 6 minute walk distance (6MWD) ≤ 450m

• Deemed eligible per Eligibility Review Committee (ERC)

• if treated in France, subject must be entitled to French social security.

Exclusion Criteria:

• Known sensitivity to drugs required for performing bronchoscopy or in whom bronchoscopic procedures are contraindicated

• Evidence of active infection in the lungs

• Hypersensitivity or allergy to nitinol (nickel-titanium) or its constituent metals

• Clinical significant pulmonary fibrosis

• Clinically significant, generalized bronchiectasis

• Clinically significant bleeding disorders

• Patient taking immunosuppresive drugs other than steroids (e.g., for the treatment of cancer, rheumatoid arthritis, autoimmune disease, or prevention of tissue or organ rejection).

• Primary diagnosis of asthma

• Two (2) or more COPD exacerbations in the prior year, or 1 or more COPD exacerbations in the prior 3 months with indication for hospitalization assessment, according to GOLD 2017 recommendations .

• Predominant small airways disease defined as significant bronchiectasis with sputum production (> 2 tablespoons daily) or significant bronchial wall thickening per High Resolution Computed Tomography (HRCT)

• Percent Low Attenuation Area (%LAA) < 20% in the most damaged lobe of either lung.

• Computed Tomography (CT) Imaging consistent with active pulmonary infection, significant interstitial disease or pleural disease

• Severe bullous disease (defined by bulla > 8cm or 1/3 of lung volume, or single bullous defect >8 cm) or predominant paraseptal emphysema [defined by numerous large (>1cm) paraseptal defects in the target lobe comprising of >5% of total lung volume].

• Lung pathology of nodule not proven stable or benign

• Radiographic confirmation of atelectasis or other scarring/fibrosis in areas of intended Coil implant

• Use of more than 20 mg/day prednisolone or equivalent dosage of a different corticosteroid

• Severe pulmonary hypertension (Right Ventricular Systolic Pressure (RVSP) > 50 mm Hg or other signs of Pulmonary Hypertension (PHT) with right ventricular dysfunction)

• Severe hypercapnia (PaCO2 > 55 mmHg on room air) and/or severe hypoxemia (PaO2 < 45mm Hg on room air, High altitude criterion: PaO2 < 30 mm Hg)

• Previous Lung Volume Reduction (LVR) surgery, lung transplantation, lobectomy, LVR devices or other device to treat COPD in either lung.

• Diagnosed with alpha-1 antitrypsin deficiency

• Diffusion Capacity of the lungs for Carbon Monoxide (DLCO) < 20 %

• Significant, recent or unstable cardiac disease defined as severe heart failure (Left Ventricular Ejection Fraction (LVEF) < 45% despite optimal medical management), unstable cardiac arrhythmia or coronary artery disease (angina on activity), or ischemic event in the past 6 months.

• Body Mass Index (BMI) > 30

• Participation in any other clinical Study.

• Subject is pregnant or lactating, or plan to become pregnant within the study timeframe.

• If treated in France, Subject is a "personne vulnerable" as defined by French Regulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ludwig Boltzmann Institut Fur COPD und pneumologische Epidemologie	Wien		Austria
2	CHU Grenoble	Grenoble		France
3	CHU Montpellier	Montpellier		France
4	Centre Hospitalier Universitaire de Nice	Nice		France	CS 51069
5	Hôpital Bichat	Paris		France
6	CHU de Reims - Hopital Maison Blanche	Reims		France	51092
7	Nouvel Hôpital Civil	Strasbourg		France	67091
8	Charite Berlin - Medizinische Klinik mit Schwerpunkt Infektiologie und Pneumologie	Berlin		Germany
9	Gemeinschaftskrankenhaus Havelhöhe GmbH	Berlin		Germany
10	Universitätsklinkum Bonn	Bonn		Germany
11	Ruhrlandklinik Essen	Essen		Germany
12	Thoraxklinik	Heidelberg		Germany
13	Lungenklinik	Hemer		Germany
14	Lungenfachklinik Immenhausen	Immenhausen		Germany	34376
15	Klinikverbund Kempten-Oberallgäu	Immenstädt		Germany
16	Krankenhaus vom Roten Kreuz Bad Cannstatt GmbH	Stuttgart		Germany
17	Ospedale Careggi	Firenze		Italy
18	University Medical Center Groningen	Groningen		Netherlands	3150-3610536
19	Royal Brompton Hospital	London		United Kingdom

Sponsors and Collaborators

• Boston Scientific Corporation
• PneumRx, Inc.

Investigators

• Principal Investigator: Felix Herth, MD,, University Hospital Heidelberg
• Principal Investigator: Arschang Valipour, MD,FCCP,PhD, Nord-Klinik Floridsdorf

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 4, 2020

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT03360396
• Other Study ID Numbers: BTG-004517-01
• First Posted: Dec 4, 2017
• Last Update Posted: Aug 15, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Boston Scientific Corporation: severe heterogeneous emphysema; severe homogeneous emphysema
• Additional relevant MeSH terms: Pulmonary Emphysema; Emphysema

Study Results

Participant Flow

Arm/Group Title	Endobronchial Coils	Control
Arm/Group Description	Treatment with PneumRx Endobronchial Coil System Endobronchial Coils: Endobronchial Coil implants	Medically-managed control group
Period Title: Overall Study
STARTED	80	40
COMPLETED	0	0
NOT COMPLETED	80	40

Baseline Characteristics

Arm/Group Title	Endobronchial Coils	Control	Total
Arm/Group Description	Treatment with PneumRx Endobronchial Coil System Endobronchial Coils: Endobronchial Coil implants	Medically-managed control group	Total of all reporting groups
Overall Participants	80	40	120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (7.51)	62.8 (7.06)	63.2 (7.34)
Sex: Female, Male (Count of Participants)
Female	41 51.3%	21 52.5%	62 51.7%
Male	39 48.8%	19 47.5%	58 48.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.3%	0 0%	1 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	78 97.5%	40 100%	118 98.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.3%	0 0%	1 0.8%
Forced Expiratory Volume in 1 second (FEV1) (Litres) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Litres]	0.8 (0.2026)	0.8 (0.2220)	0.8 (0.21)
St. George Respiratory Questionnaire Score (SGRQ) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	59.327 (11.4232)	54.666 (14.5222)	57.8 (12.67)

Outcome Measures

1. Primary Outcome

Title	Percent Change in FEV1 at 6 Months
Description	Percent change in FEV1
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Endobronchial Coils	Control
Arm/Group Description	Treatment with PneumRx Endobronchial Coil System Endobronchial Coils: Endobronchial Coil implants	Medically-managed control group
Measure Participants	57	34
Mean (Standard Deviation) [percent change from baseline]	12.745 (33.1782)	-2.604 (10.1628)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Endobronchial Coils, Control
	Comments	Study was closed early in all regions except for France. Statistical Analysis plan was updated to include descriptive statistics only. Sites in France remain open and all subjects in France will be followed through 36 months.
	Type of Statistical Test	Other
	Comments	Study was closed early in all regions except for France. Statistical Analysis plan was updated to include descriptive statistics only. Sites in France remain open and all subjects in France will be followed through 36 months.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Study was closed early in all regions except for France. Statistical Analysis plan was updated to include descriptive statistics only. Sites in France remain open and all subjects in France will be followed through 36 months.

2. Primary Outcome

Title	Absolute Change in SGRQ Score at 6 Months
Description	Change in SGRQ score - St. George Respiratory Questionnaire from 0 to 100, higher score indicating more limitations (worse), increase in score indicating worse outcome, decrease in score indicating improvement
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Endobronchial Coils	Control
Arm/Group Description	Treatment with PneumRx Endobronchial Coil System Endobronchial Coils: Endobronchial Coil implants	Medically-managed control group
Measure Participants	54	33
Mean (Standard Deviation) [score on a scale]	-8.561 (14.6834)	2.080 (9.8483)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Endobronchial Coils, Control
	Comments	Study was terminated early, and Statistical Analysis plan was updated to include descriptive statistics only.
	Type of Statistical Test	Other
	Comments	Study was terminated early, and Statistical Analysis plan was updated to include descriptive statistics only.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Study was terminated early, and Statistical Analysis plan was updated to include descriptive statistics only.

3. Other Pre-specified Outcome

Title	Efficacy Analyses Post Primary Endpoint
Description	Descriptive statistics will summarize effectiveness endpoints at 12 and 36 months for all coil treated subjects in France.
Time Frame	12 and 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	6 months
Arm/Group Title	Endobronchial Coils		Control
Arm/Group Description	Treatment with PneumRx Endobronchial Coil System Endobronchial Coils: Endobronchial Coil implants		Medically-managed control group
All Cause Mortality
	Endobronchial Coils		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/73 (6.8%)		0/40 (0%)
Serious Adverse Events
	Endobronchial Coils		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/73 (41.1%)		3/40 (7.5%)
Cardiac disorders
atrial fibrillation	1/73 (1.4%)	1	0/40 (0%)	0
Gastrointestinal disorders
abdominal pain	1/73 (1.4%)	1	0/40 (0%)	0
constipation	1/73 (1.4%)	1	0/40 (0%)	0
General disorders
death	1/73 (1.4%)	1	0/40 (0%)	0
Infections and infestations
Pneumonia	8/73 (11%)	8	0/40 (0%)	0
Bronchitis	1/73 (1.4%)	1	0/40 (0%)	0
Enterococcal infection	1/73 (1.4%)	1	0/40 (0%)	0
Influenza	1/73 (1.4%)	1	0/40 (0%)	0
Respiratory Tract Infection	1/73 (1.4%)	1	0/40 (0%)	0
urosepsis	1/73 (1.4%)	1	0/40 (0%)	0
infective exacerbation of COPD	0/73 (0%)	0	1/40 (2.5%)	1
nasopharyngitis	0/73 (0%)	0	1/40 (2.5%)	1
Injury, poisoning and procedural complications
road traffic accident	1/73 (1.4%)	1	0/40 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
lung neoplasm malignant	1/73 (1.4%)	1	0/40 (0%)	0
prostate cancer	0/73 (0%)	0	1/40 (2.5%)	1
renal cancer	1/73 (1.4%)	1	0/40 (0%)	0
Product Issues
device dislocation	1/73 (1.4%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	3/73 (4.1%)	3	3/40 (7.5%)	3
Pneumothorax	3/73 (4.1%)	3	0/40 (0%)	0
Dypsnoea	2/73 (2.7%)	2	0/40 (0%)	0
Respiratory Failure	2/73 (2.7%)	3	0/40 (0%)	0
Haemoptysis	1/73 (1.4%)	1	0/40 (0%)	0
Hypercapnea	1/73 (1.4%)	1	0/40 (0%)	0
Pulmonary Embolism	1/73 (1.4%)	1	0/40 (0%)	0
Respiratory Disorder	1/73 (1.4%)	1	0/40 (0%)	0
Respiratory Distress	1/73 (1.4%)	1	0/40 (0%)	0
Other (Not Including Serious) Adverse Events
	Endobronchial Coils		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/73 (53.4%)		12/40 (30%)
Ear and labyrinth disorders
Ear Haemorrhage	1/73 (1.4%)	1	0/40 (0%)	0
Gastrointestinal disorders
Gastrointestinal Tract Irritation	1/73 (1.4%)	1	0/40 (0%)	0
General disorders
Chest Pain	10/73 (13.7%)	12	0/40 (0%)	0
Fatigue	1/73 (1.4%)	1	0/40 (0%)	0
Non-Cardiac Chest Pain	1/73 (1.4%)	1	0/40 (0%)	0
Infections and infestations
bronchitis	8/73 (11%)	9	4/40 (10%)	4
Escherichia Urinary Tract Infection	0/73 (0%)	0	1/40 (2.5%)	1
Infected Dermal Cyst	1/73 (1.4%)	1	0/40 (0%)	0
Influenza	1/73 (1.4%)	1	1/40 (2.5%)	1
Lower Respiratory Tract Infection	1/73 (1.4%)	1	0/40 (0%)	0
Lung Infection	1/73 (1.4%)	1	0/40 (0%)	0
Nasopharyngitis	2/73 (2.7%)	2	0/40 (0%)	0
Oral Candidiasis	1/73 (1.4%)	1	0/40 (0%)	0
Pneumonia	10/73 (13.7%)	11	0/40 (0%)	0
Tooth Abscess	1/73 (1.4%)	1	0/40 (0%)	0
Tooth Infection	0/73 (0%)	0	1/40 (2.5%)	2
Urinary Tract Infection	1/73 (1.4%)	1	0/40 (0%)	0
Injury, poisoning and procedural complications
Procedural Haemorrhage	1/73 (1.4%)	1	0/40 (0%)	0
Radius Fracture	1/73 (1.4%)	1	0/40 (0%)	0
Metabolism and nutrition disorders
Vitamin D Deficiency	1/73 (1.4%)	1	0/40 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	1/73 (1.4%)	1	0/40 (0%)	0
Osteoarthritis	0/73 (0%)	0	1/40 (2.5%)	1
Osteoporosis	1/73 (1.4%)	1	0/40 (0%)	0
Renal and urinary disorders
Urinary Retention	1/73 (1.4%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/73 (1.4%)	1	0/40 (0%)	0
Chronic Obstructive Pulmonary Disease	11/73 (15.1%)	13	5/40 (12.5%)	5
Cough	2/73 (2.7%)	2	0/40 (0%)	0
Dyspnoea	6/73 (8.2%)	8	0/40 (0%)	0
Haemoptysis	20/73 (27.4%)	28	0/40 (0%)	0
Pneumothorax	1/73 (1.4%)	1	0/40 (0%)	0
Pulmonary Pain	1/73 (1.4%)	1	0/40 (0%)	0
Vascular disorders
Hypertension	0/73 (0%)	0	1/40 (2.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.