The primary objective of this prospective study in subjects with severe emphysema is to evaluate the utility of the AeriSeal System to occludecollateral air channels in a target lung lobe with collateral ventilation (CV+) and convert the target lung…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Stage 1 (Post-AeriSeal):
The Primary AeriSeal Endpoint is the percentage of study subjects that are
successfully converted from a positive collateral ventilation status
(CV+) in the treated lobe to having little to no collateral ventilation (CV-)
by Chartis in the treated lobe, six (6) weeks after delivery of AeriSeal.
Stage 2 (Post-Zephyr Valves):
The Primary Zephyr Valve Endpoint is the percent of subjects achieving Treated
Lobar Volume Reduction (TLVR) >= 350 mL at 45- days post successful lobar
occlusion with Zephyr Valves.
Secondary outcome
Secondary:
o Post-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) change from
Baseline to 3-months (Absolute and Percent).
o Residual volume (RV) change from Baseline to 3-months (Absolute and Percent).
Additional:
o Post-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) change from
Baseline to 6 and 12 months (Absolute and Percent).
o Residual volume (RV) change from Baseline to 6 and 12 months (Absolute and
Percent).
o Six-Minute Walk Distance (6MWD) change from Baseline to 3-months, 6-months
and 12 months.
o St. George*s Respiratory Questionnaire (SGRQ) score change from Baseline to
3-months, 6-months and 12 months.
o Modified Medical Research Council Dyspnea Score (mMRC) change from Baseline
to 3-months, 6-months and 12 months.
o Absolute and percent changes in TLC and IC from Baseline to 3-months,
6-months and 12 months.
o Changes in RV/TLC and IC/TLC from Baseline to 3-months, 6-months and 12
months. (Absolute and Percent).
o TLVR at 6-Months and 12 months.
Background summary
Patients with severe emphysema and hyperinflation may be eligible for treatment
with endobronchial valves and may lead to improvement of lung function,
exercise capacity and quality of life. This is only possible if there is no
collateral ventilation between the treatment target lobe and the contralateral
lobe.
Most patients have collateral ventilation and cannot be treated with valves. If
the collateral ventilation could be blocked, patients might be eligible for
treatment.
This study is to investigate the feasibility of closing the collateral
ventilation channels by AeriSeal to convert positive collateral ventilation to
negative collateral ventilation, to see if treatment with endobronchial valves
is possible after closure of the collateral channels.
Study objective
The primary objective of this prospective study in subjects with severe
emphysema is to evaluate the utility of the AeriSeal System to occlude
collateral air channels in a target lung lobe with collateral ventilation (CV+)
and convert the target lung lobe to having little to no collateral
ventilation (CV-). A secondary objective is to perform bronchoscopic lung
volume reduction (BLVR) with placement of commercially available Zephyr
Valves in the target lobe, successfully converted from positive collateral
ventilation (CV+) status to having little to no collateral ventilation (CV-).
Subjects who are successfully converted to CV- after treatment with AeriSeal
will follow the standard of care for CV- emphysema and be
treated with the CE marked Zephyr Valve(s) according to the Zephyr IFU, to
achieve lung volume reduction.
Study design
This is a prospective, open-label, multi-center, single-arm study to be
conducted at up to 15 investigational sites.
Intervention
1) Stage 1 will address the closure of the lobar fissure gaps (or collateral
air channels) to block collateral ventilation with the AeriSeal System
2) Stage 2 will include successfully converted subjects; CV+ to CVconversion in
Stage 1. Converted CV- target lobes will follow standard of care and receive CE
marked Zephyr Endobronchial valves per the Zephyr IFU to perform bronchoscopic
lung volume reduction (BLVR).
Study burden and risks
It is possible that the patients will not receive any benefit from
participation in this trial if the procedure will not lead to a conversion to
CV(-). Risks associated with the Chartis measurement and the placement of EBVs
mainly include the risk associated with routine bronchoscopy, like sore throat
and bronchitis. The placement of the EBV is associated with an increased risk
of a pneumothorax. The specific risks to the use of the transbronchial
administration of AeriSeal include infective COPD exacerbation and pneumonia.
The patients who will participate in this trial have limited treatment options.
Due to the phenotype of the COPD and emphysema with incomplete fissures there
are no other possible regular bronchoscopic interventions at the moment.
Patients will only be offered entry into the CONVERT trial if the consensus
decision of the bronchoscopic intervention is that participating in this trial
is the best option for the patient. Other trials have shown that bronchoscopy
is a very safe procedure in severe emphysema patients. The injection of
AeriSeal could potentially successful convert CV(+) to CV(-) and consequently
the patient can be treated with the EBV. Potentially, BLVR could result in the
majority of patients in a clinical significant increase in FEV1 and FVC, with
decreasing RV, resulting in a significant reduction in dyspnea and improvement
in quality of life, and a better exercise tolerance.
Chesapeake Drive 700
Redwood City CA 94063
US
Chesapeake Drive 700
Redwood City CA 94063
US
Listed location countries
Age
Inclusion criteria
Inclusion Criteria
1. Subject is willing and able to provide Informed Consent and to participate
in the study.
2. Subject is >= 40 and <= 75 years of age at the time Informed Consent signature.
3. Subject has at least one lobe with >= 50% emphysema destruction (at *910 HU)
as determined
by QCT.
4. Subject has a diagnosis of homogenous or heterogeneous emphysema, confirmed
by HRCT
scan. Heterogeneous emphysema defined as >= 15% difference (at -910 HU) in
emphysema
destruction score of adjacent lobes by HRCT.
5. Subject has a gap in the interlobar fissure that corresponds to one or more
segments as
determined by QCT.
6. Subject has clinically significant dyspnea with a mMRC Dyspnea score >= 2.
7. Subject has a Six-Minute Walk Distance >= 250 meters.
8. Subject has post-bronchodilator FEV1 >= 15% predicted and <= 50% predicted.
9. Subject has post-bronchodilator Total Lung Capacity >= 100% predicted.
10. Subject has post-bronchodilator Residual Volume >= 150% predicted if
heterogeneous
emphysema and >= 200% predicted if homogeneous emphysema.
11. Subject has stopped smoking for at least eight (8) weeks prior to Screening
visit as confirmed
by carboxyhemoglobin or cotinine levels.
12. Subject has received preventive vaccinations against potential respiratory
infections
consistent with local recommendations or policy.
Exclusion criteria
Exclusion Criteria
1. Subject has severe bullous emphysema where bulla is >= 1/3 of the total lung
volume.
2. Subject has had prior lung volume reduction surgery, prior lobectomy or
pneumonectomy,
prior lung transplantation, prior airway stent placement, prior ipsilateral
pleurodesis, or prior
endobronchial lung volume reduction therapy of any type.
3. Subject has evidence of active respiratory infection.
4. Subject has an ongoing COPD exacerbation or bronchospasm.
5. Subject has a known allergy to the device components:
a. Polyether block amide - PEBAX®
b. Polyvinyl Alcohol
c. Glutaraldehyde
d. Nitinol (nickel-titanium) or its constituent metals (nickel or titanium)
e. Silicone
6. Subject requires ventilatory support (invasive or non-invasive).
7. Subject has post-bronchodilator Diffusion Capacity (DLCO) < 20% predicted.
8. Subject cannot tolerate corticosteroids or relevant antibiotics.
9. Subject has other relevant comorbidities as judged by the Investigator or is
deconditioned
and cannot tolerate the stress of post-treatment inflammatory response.
10. Subject has had three (3) or more COPD exacerbations requiring
hospitalization during the
year prior to Informed Consent signature.
11. Subject has severe gas exchange abnormalities as defined by any one of the
following (test
conducted at rest on room air as tolerated, or on up to 4 L/min supplemental O2)
a. PaCO2 >= 55 mm Hg (7.3 kPa)
b. PaO2 < 45 mm Hg (6.0 kPa)
c. SpO2 < 90%
12. Subject has uncontrolled pulmonary hypertension, defined as peak pulmonary
systolic
pressure > 45 mm Hg on echocardiogram or right heart catheterization.
13. Subject use of systemic steroids > 20 mg/day prednisolone or equivalent
within 4 weeks of
Informed Consent signature.
14. Subject use of immunosuppressive agents within four (4) weeks of Informed
Consent
signature.
15. Subject whose use heparins and oral anticoagulants (e.g., warfarin,
dicumarol) cannot be
discontinued according to local pre-procedural protocols. Note: antiplatelet
drugs including
aspirin and clopidogrel are permitted.
16. Subject*s CT scan indicates the presence of any the following radiologic
abnormalities:
a. Pulmonary nodule on CT scan greater than 0.8 cm in diameter (Does not apply
if
present for one (1) year or more without increase in size or if proven benign by
biopsy).
b. Radiologic picture consistent with active pulmonary infection, e.g.,
unexplained
parenchymal infiltrate.
c. Significant interstitial lung disease.
d. Significant pleural disease.
17. Subject*s baseline EKG indicates non-atrial arrhythmias or conduction
abnormalities.
18. Subject has high cardiac risk after undergoing cardiac risk assessment in
accordance with
published guidelines18 or ischemic heart disease, congestive heart failure,
renal failure, or
cerebrovascular disease.
19. Subject has clinically significant asthma (reversible airway obstruction),
chronic
bronchitis, or bronchiectasis.
20. Subject has allergy or sensitivity to medications required to safely
perform bronchoscopy
under conscious sedation or general anesthesia.
21. Subject participated in an investigational study of a drug, biologic, or
device not currently
approved for marketing within 30 days prior to Screening visit. Subjects being
followed as
part of a long-term surveillance of a non-pulmonary study that has reached its
primary
endpoint are eligible for participation in this study.
22. Subject has Body Mass Index (BMI) < 18 kg/m2 or > 35 kg/m2.
23. Subject is a female who is pregnant, breast-feeding, or planning to be
pregnant in next 12
months.
24. Subject has clinically significant abnormal screening laboratory test
results per the
Institution specific reference laboratory normal values for the following:
a. White blood cells (total)
b. Hematocrit
c. Platelets
d. Prothrombin time or INR
e. Partial thromboplastin time
f. Positive β-HCG Pregnancy test (if female)
25. Subject has evidence of severe disease which in the judgment of the
Investigator may
compromise survival for the duration of the study (at least 12 months) e.g.:
a. HIV/AIDs
b. Active malignancy
c. Stroke or Transient Ischemic attack (TIA) within 12 months of Screening visit
d. Myocardial infarction within six (6) months of the Screening visit
e. Congestive heart failure within six (6) months of the Screening visit
defined as
clinical evidence of right or left heart failure or left ventricular ejection
fraction <
45% on echocardiogram
26. Subject has uncontrolled diabetes mellitus.
27. Subject has any other condition that the Investigator believes would
interfere with the intent
of the study or would make participation not in the best interest of the
subject including
but not limited to alcoholism, high risk for drug abuse, or noncompliance in
returning for
follow-up visits.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04559464 |
| CCMO | NL75325.042.20 |