Improving Patient Outcomes by Selective Implantation of the Zephyr EBV - Study

A Multicentre, Prospective, Randomized, Controlled, One-way Crossover Investigation of Endobronchial Valve (EBV) Therapy vs. Standard of Care (SoC) in Homogeneous Emphysema

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02025205

Acronym

IMPACT

Enrollment

Registered

2013-12-31

Start date

2014-08-31

Completion date

2017-03-15

Last updated

2019-08-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD Patients With Homogeneous Emphysema, Endoscopic Lung Volume Reduction With Endobronchial Valve

Brief summary

The aim of this prospective, randomized, controlled, one-way crossover study is to assess and compare the efficacy of the Zephyr endobronchial valves vs. Standard of Care (SoC) in patients suffering from COPD with Homogeneous Emphysema. Patients will be followed up for 12 months after randomization. Patients in the SoC arm will crossover to the EBV treatment arm after the 6-month visit and will be followed up for 6 additional months.The primary objective is the variation of FEV1 between baseline and 3-month follow-up visit. The secondary objectives will evaluate quality of life, exercise capacity, dyspnea (including BODE index) changes, target lobe volume reduction, as well as safety outcomes.

Interventions

DEVICEEndobronchial Valve

Endoscopic Lung Volume Reduction with Zephyr Endobronchial Valve

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

* Homogeneous emphysema * 15% ≤ FEV1 ≤ 45% predicted * TLC \> 100% predicted * RV ≥ 200% predicted * 6MWT ≥ 150 m * Non-smoker \> 8 weeks prior to study entry * Absence of Collateral Ventilation in the target lobe

Exclusion criteria

* Active pulmonary infection * More than 3 exacerbations with hospitalizations over the past 12 months * Pulmonary hypertension (sPAP \> 45 mmHg) * MI or other relevant CV events in the past 6 months * Alpha-1 antitrypsin deficiency * Bronchiectasis * Prior LVR or LVRS procedure * \> 20% difference in perfusion between right and left lung * Hypercapnia (paCO2 \> 55 mmHg * Asthma * Use of more than 25 mg/day prednisolone or equivalent * Severe bullous emphysema * Systemic or malignant disease with high death probability within 12 months

Design outcomes

Primary

Measure	Time frame	Description
Percentage Change in Forced Expiratory Volume in 1 s (FEV1) (ITT Population)	At baseline and after 3 months	Percentage change in FEV1 at 3 months relative to Baseline in the EBV group, compared to the SoC group.

Secondary

Measure	Time frame	Description
Percent Change in Target Lobe Volume for EBV Group (ITT Population)	At baseline and after 3 months	Target Lobe Volume Reduction (TLVR) was evaluated by quantitative analysis of HRCT scans at Baseline and at 3-months post-valve placement to measure the target lobe volume.
Percent of Subjects in the EBV Group With a Target Lobe Volume Reduction (TLVR) of ≥ 350ml at 3 Months	At baseline and after 3 months	The threshold of TLVR ≥350 mL was used to determine the proportion of subjects that achieved this amount of TLVR in the EBV group.
Absolute Change in FEV1 (L) Post Bronchodilator at 3 Months	At baseline and after 3 months	The mean absolute change in FEV1(L) relative to Baseline at 3 months between the EBV and SoC groups
Absolute Change in FEV1 (% Predicted) Post Bronchodilator at 3 Months	At baseline and after 3 months	The mean absolute change in FEV1(% Predicted) relative to Baseline at 3 months between the EBV and SoC groups
Absolute Change in Residual Volume (RV) at 3 Months	At baseline and after 3 months	Mean absolute change in Residual Volume relative to Baseline at 3 months between the EBV and SoC groups
Percent Change in Residual Volume (RV) at 3 Months	At baseline and after 3 months	Mean percent change in Residual Volume relative to Baseline at 3 months between the EBV and SoC groups
Percent Predicted Change in Residual Volume at 3 Months	At baseline and after 3 months	Percent predicted change in RV relative to Baseline at 3 months between the EBV and SoC groups
Absolute Change in Six-Minute Walk Distance at 3 Months	At baseline and after 3 months	Mean absolute change in the 6MWD from Baseline to 3 months in the EBV group compared to the SOC
Percent Change in Six-Minute Walk Distance at 3 Months	At baseline and after 3 months	Mean percent change in the 6MWD from Baseline to 3 months in the EBV group compared to the SOC
Absolute Change in Target Lobe Volume for EBV Group (ITT Population)	At baseline and after 3 months	Target Lobe Volume Reduction (TLVR) was evaluated by quantitative analysis of HRCT scans at Baseline and at 3-months post-valve placement to measure the target lobe volume.
Percent Change (%) in the SGRQ Total Score From Baseline to 3 Months	At baseline and after 3 months	Mean percent change in the SGRQ Total Score from Baseline to 3 months in the EBV group compared to the SoC group
Absolute Change in the mMRC Dyspnea Score From Baseline to 3 Months	At baseline and after 3 months	Mean absolute change in the Modified Medical Research Council (mMRC) Dyspnea Score from Baseline to 3 months in the EBV group compared to the SoC group. The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations.
Percent Change (%) in EQ-5D Summary Index From Baseline to 3 Months	At baseline and after 3 months	Mean percent change in EQ-5D Summary Index from Baseline to 3 months in the EBV group compared to the SoC group.
Percent Change (%) in the mMRC Dyspnea Score From Baseline to 3 Months	At baseline and after 3 months	Mean percent change in the mMRC Dyspnea Score from Baseline to 3 months in the EBV group compared to the SoC group. The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations.
Absolute Change in the CAT Total Score From Baseline to 3 Months	At baseline and after 3 months	Mean absolute change in the COPD Assessment Test (CAT) Total Score from Baseline to 3 months in the EBV group compared to the SoC group. The COPD Assessment Test (CAT) is an eight-item questionnaire designed to quantify the impact of COPD symptoms on the health status of patients. The CAT provides a score of 0-40 to indicate the impact of disease.
Percent Change (%) in CAT Total Score From Baseline to 3 Months	At baseline and after 3 months	The COPD Assessment Test (CAT) is an eight-item questionnaire designed to quantify the impact of COPD symptoms on the health status of patients. The CAT provides a score of 0-40 to indicate the impact of disease. Higher scores denote a more severe impact of COPD on a patient's life.
Absolute Change in EQ-5D Summary Index From Baseline to 3 Months	At baseline and after 3 months	Mean absolute change in the EQ-5D Summary Index from Baseline to 3 months in the EBV group compared to the SoC group. EQ-5D is a standardized instrument to measure health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D health states may be converted into a single summary index by applying a formula that attaches weights to each of the levels in each dimension. The maximum score of 1 indicates the best health state, while 0 indicates the worst health state.
Absolute Change in EQ-5D VAS (Health State Today) Score From Baseline to 3 Months	At baseline and after 3 months	Mean absolute change in the EQ-5D VAS (Health State Today) Score from Baseline to 3 months in the EBV group compared to the SoC group. Scores range from 0 to 100, with higher scores indicating better outcome.
Absolute Change in the SGRQ Total Score From Baseline to 3 Months	At baseline and after 3 months	Mean absolute change in the St. George's Respiratory Questionnaire Total Score from Baseline to 3 months in the EBV group compared to the SoC group. Scores range from 0 to 100, with higher scores indicating more limitations.

Countries

Austria, Germany, Netherlands

Participant flow

Participants by arm

Arm	Count
ELVR With Endobronchial Valves Endoscopic Lung Volume Reduction with Zephyr Endobronchial Valve Endobronchial Valve: Endoscopic Lung Volume Reduction with Zephyr Endobronchial Valve	43
Standard of Care Patients will receive optimal drug therapy and medical management according to clinical practice.	50
Total	93

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	0	1
Overall Study	Protocol Violation	2	1
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Total	ELVR With Endobronchial Valves	Standard of Care
6 Minute Walk Distance (meters)	318.9 meters STANDARD_DEVIATION 92.1	308.0 meters STANDARD_DEVIATION 91.3	328.3 meters STANDARD_DEVIATION 92.6
Age, Continuous	63.7 years STANDARD_DEVIATION 6.1	64.3 years STANDARD_DEVIATION 6.3	63.2 years STANDARD_DEVIATION 6
BMI	23.1 kg/m^2 STANDARD_DEVIATION 4	23.7 kg/m^2 STANDARD_DEVIATION 4.3	22.6 kg/m^2 STANDARD_DEVIATION 3.7
BODE index	5.4 points on a scale STANDARD_DEVIATION 1.6	5.7 points on a scale STANDARD_DEVIATION 1.4	5.2 points on a scale STANDARD_DEVIATION 1.7
Emphysema score	66.8 percent STANDARD_DEVIATION 7.3	68.0 percent STANDARD_DEVIATION 7.5	65.8 percent STANDARD_DEVIATION 6.9
EQ-5D Anxiety/Depression Extreme	11 Participants	9 Participants	2 Participants
EQ-5D Anxiety/Depression Moderate	40 Participants	16 Participants	24 Participants
EQ-5D Anxiety/Depression No	38 Participants	16 Participants	22 Participants
EQ-5D health state today	45.2 score STANDARD_DEVIATION 17.7	40.3 score STANDARD_DEVIATION 14.4	49.3 score STANDARD_DEVIATION 19.3
EQ-5D Mobility Confined to bed	1 Participants	1 Participants	0 Participants
EQ-5D Mobility No problems	23 Participants	8 Participants	15 Participants
EQ-5D Mobility Some problems	65 Participants	32 Participants	33 Participants
EQ-5D Pain/Discomfort Extreme	7 Participants	3 Participants	4 Participants
EQ-5D Pain/Discomfort Moderate	36 Participants	20 Participants	16 Participants
EQ-5D Pain/Discomfort No	44 Participants	16 Participants	28 Participants
EQ-5D Self-Care No problems	40 Participants	13 Participants	27 Participants
EQ-5D Self-Care Some problems	46 Participants	25 Participants	21 Participants
EQ-5D Self-Care Unable	3 Participants	3 Participants	0 Participants
EQ-5D Summary Index	0.6 points on a scale STANDARD_DEVIATION 0.3	0.5 points on a scale STANDARD_DEVIATION 0.3	0.6 points on a scale STANDARD_DEVIATION 0.2
EQ-5D usual activities No problems	7 Participants	2 Participants	5 Participants
EQ-5D usual activities Some problems	64 Participants	32 Participants	32 Participants
EQ-5D usual activities Unable	18 Participants	7 Participants	11 Participants
FEV1/FVC (%)	36.0 percent STANDARD_DEVIATION 7.9	36.3 percent STANDARD_DEVIATION 7.2	35.8 percent STANDARD_DEVIATION 8.6
FEV1 (liters)	0.8 Liters STANDARD_DEVIATION 0.2	0.8 Liters STANDARD_DEVIATION 0.2	0.8 Liters STANDARD_DEVIATION 0.2
FEV1 (% predicted)	29.3 % predicted STANDARD_DEVIATION 6.5	28.4 % predicted STANDARD_DEVIATION 6.3	30.0 % predicted STANDARD_DEVIATION 6.6
Gold stage Gold Stage III	41 Participants	18 Participants	23 Participants
Gold stage Gold Stage IV	52 Participants	25 Participants	27 Participants
Height	166.9 cm STANDARD_DEVIATION 9.6	168.7 cm STANDARD_DEVIATION 10	165.4 cm STANDARD_DEVIATION 9.1
Heterogeneity index	5.9 units on a scale STANDARD_DEVIATION 6	6.8 units on a scale STANDARD_DEVIATION 5.7	5.0 units on a scale STANDARD_DEVIATION 6.3
mMRC Dyspnea Grade score	2.5 points on a scale STANDARD_DEVIATION 0.9	2.7 points on a scale STANDARD_DEVIATION 0.8	2.4 points on a scale STANDARD_DEVIATION 1
Pack Years Smoking History	42.0 pack-years STANDARD_DEVIATION 20.8	41.5 pack-years STANDARD_DEVIATION 19.6	42.5 pack-years STANDARD_DEVIATION 22
Region of Enrollment Austria	21 participants	8 participants	13 participants
Region of Enrollment Germany	49 participants	26 participants	23 participants
Region of Enrollment Netherlands	23 participants	9 participants	14 participants
Residual Volume (RV) (Liters)	5.5 Liters STANDARD_DEVIATION 1.2	5.7 Liters STANDARD_DEVIATION 1.1	5.2 Liters STANDARD_DEVIATION 1.2
Residual Volume (RV) (% predicted)	275.4 % predicted STANDARD_DEVIATION 59.4	277.3 % predicted STANDARD_DEVIATION 55.2	273.7 % predicted STANDARD_DEVIATION 63.4
RV/TLC (%)	68.6 percent STANDARD_DEVIATION 6.7	69.0 percent STANDARD_DEVIATION 6.3	68.2 percent STANDARD_DEVIATION 7.1
Sex: Female, Male Female	57 Participants	23 Participants	34 Participants
Sex: Female, Male Male	36 Participants	20 Participants	16 Participants
SGRQ Total Score	61.1 points on a scale STANDARD_DEVIATION 14.8	63.2 points on a scale STANDARD_DEVIATION 13.7	59.3 points on a scale STANDARD_DEVIATION 15.6
The COPD Assessment Test (CAT) total score (derived)	23.1 points on a scale STANDARD_DEVIATION 6.3	23.4 points on a scale STANDARD_DEVIATION 6.8	22.8 points on a scale STANDARD_DEVIATION 6
Total Lung Capacity (TLC) (Liters)	8.0 Liter STANDARD_DEVIATION 1.5	8.4 Liter STANDARD_DEVIATION 1.6	7.6 Liter STANDARD_DEVIATION 1.4
Total Lung Capacity (TLC) (% predicted)	144.6 % predicted STANDARD_DEVIATION 19.3	144.9 % predicted STANDARD_DEVIATION 21.2	144.2 % predicted STANDARD_DEVIATION 17.6
Weight	64.8 kg STANDARD_DEVIATION 13.9	67.9 kg STANDARD_DEVIATION 15.4	62.2 kg STANDARD_DEVIATION 12

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	30 / 43	22 / 50
serious Total, serious adverse events	28 / 43	16 / 50

Outcome results

Primary

Percentage Change in Forced Expiratory Volume in 1 s (FEV1) (ITT Population)

Percentage change in FEV1 at 3 months relative to Baseline in the EBV group, compared to the SoC group.