Collateral Ventilation Effects on Response to AeriSeal System Treatment in Upper Lobe Predominant Emphysema (CV+/-)

This study will evaluate the effects of baseline collateral ventilation status on outcomes following treatment with AeriSeal System in patients with advanced upper-lobe predominant heterogenous emphysema.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Emphysema
• Intervention / Treatment: Device: Emphysematous Lung Sealant

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH
  • Berlin, Germany, 10117
    • Charité Campus Virchow-Klinikum
  • Coburg, Germany, 96450
    • Klinikum Coburg
  • Donaustauf, Germany, 93093
    • Klinikum Donaustauf
  • Gauting, Germany, 82131
    • Asklepios Fachkliniken Muenchen - Gauting
  • Halle, Germany, 06120
    • Universitätsklinikum Halle
  • Hamburg, Germany, 21075
    • Asklepios Klinik Hamburg-Harburg
  • Heidelberg, Germany, D-69126
    • Thoraxklinik am Uniklinikum Heidelberg
  • Luebeck, Germany, 23560
    • Sana Kliniken Luebeck
  • Munchen, Germany, 81377
    • Medizinische Klinik und Poliklinik Grosshadern
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah - Hebrew University Medical Center
  • Petach-Tikva, Israel, 49100
    • Carmel Medical Center
  • Tel Aviv, Israel, 52621
    • Chaim Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide informed consent and to participate in the study
• Age > or = 40 years at the time of the screening
• Advanced upper lobe predominant emphysema by CT scan
• Two (2) subsegments appropriate for treatment based upon CT scan in 2 different upper lobe segments in each lung (total 4 available subsegments)
• MRCD questionnaire score of 2 or greater at screening
• Failure of medical therapy to provide relief of symptoms

• Spirometry 15 minutes after administration of bronchodilator (BOTH):

  • FEV1 < 50% predicted
  • FEV1/FVC ratio < 70%

• Lung volumes by plethysmography (BOTH):

  • TLC > 100% predicted
  • RV > 150% predicted
• DLco > or = 20 and < or = 60% predicted
• Oxygen saturation (SpO2) > 90% on < or = 4 L/min supplemental O2, at rest
• Six-Minute Walk Test distance > or = 150 m
• Abstinence from smoking for at least 16 weeks prior to screening

Exclusion Criteria:

• Prior lung volume reduction surgery, prior lobectomy or pneumonectomy, prior lung transplantation, prior airway stent placement, prior pleurodesis, or prior endobronchial lung volume reduction therapy of any type
• Requirement for ventilator support (invasive or non-invasive)
• Three (3) or more COPD exacerbations requiring hospitalization within 1 year of Screening visit or a COPD exacerbation requiring hospitalization within 8 weeks of Screening visit
• α-1 antitrypsin serum level of <80 mg/dl (immunodiffusion) or <11µmol/L (nephelometry) at Screening visit in the absence of enzyme replacement therapy. Patients with documented α-1 antitrypsin deficiency requiring replacement therapy are excluded from the study participation.

• Pulmonary hypertension, defined as:

  • Echocardiogram with estimated peak systolic pressure > 45 mmHg in the presence of tricuspid valve regurgitation stated in the echocardiogram report
  • If the echocardiogram shows peak systolic pressure > 45 mmHg, right heart catheterization is required to rule out pulmonary hypertension, defined as peak systolic pressure > 45 mmHg or mean pressure > 35 mmHg
• Clinically significant asthma (reversible airway obstruction) or bronchiectasis

• CT scan: Presence of the following radiologic abnormalities:

  • Pulmonary nodule on CT scan greater that 1.0 cm in diameter (Does not apply if present for 2 years or more without increase in size or if proven benign by biopsy/PET)
  • Radiologic picture consistent with active pulmonary infection, e.g., unexplained parenchymal infiltrate
  • Significant interstitial lung disease
  • Significant pleural disease
  • Giant bullous disease (a predominant bulla > 10 cm in diameter)
• Use of systemic steroids > 20 mg/day or equivalent, immunosuppressive agents, heparins, oral anticoagulants (e.g., warfarin, dicumarol; note: antiplatelet drugs including aspirin and clopidogrel are permitted) and investigational medications within 4 weeks of screening
• Allergy or sensitivity to medications required to safely undergo AeriSeal System treatment
• Participation in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to the screening visit
• Body mass index < 15 kg/m2 or > 35 kg/m2
• Female patient pregnant or breast-feeding or planning to be pregnant in the next year

• Significant comorbidity that carries prohibitive risks or is associated with less than 2-year expected survival, including any of the following:

  • HIV/AIDS
  • Active malignancy
  • Stroke or TIA within 12 months of screening
  • Myocardial infarction within 12 months of screening
  • Congestive heart failure within 12 months of screening defined at clinical evidence of right or left hear failure or left ventricular ejection fraction < 45% on echocardiogram
• Any condition that the Investigator believes would interfere with the intent of the study or would make participation not in the best interest of the patient such as alcoholism, high risk for drug abuse or noncompliance in returning for follow-up visits

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Collateral Ventilation Positive (CV+)	Device: Emphysematous Lung Sealant; 4 Subsegments treated - 2 each bilaterally; Other Names: AeriSeal System Treatment
Active Comparator: Collateral Ventilation Negative (CV-)	Device: Emphysematous Lung Sealant; 4 Subsegments treated - 2 each bilaterally; Other Names: AeriSeal System Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in group mean post bronchodilator Forced Exhalation Volume in one second (FEV1)	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in group mean 6 Minute Walk Test (6MWT) distance		24 Weeks
Change from baseline in group mean health related quality of life	Change from baseline in group mean health related quality of life, measured in terms of St. George's Respiratory Questionnaire (SGRQ) total domain score	24 Weeks

Collaborators and Investigators

• Sponsor: Aeris Therapeutics
• Investigators: Study Director: Janine McDermott, MS CCRP, Aeris Therapeutics

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): November 14, 2013
• Last Update Submitted That Met QC Criteria: November 13, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; LVRS; Bronchoscopic Lung Volume Reduction; BLVR; Heterogeneous; Homogeneous; Upper Lobe Predominant; ULP; Lung Volume Reduction Surgery; Gold Stage III; Gold Stage IV
• 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: 03-C11-004PLV