Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01969734 |
| Other study ID # |
SFH2 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
October 21, 2013 |
| Last updated |
May 19, 2017 |
| Start date |
March 2014 |
| Est. completion date |
March 2015 |
Study information
| Verified date |
May 2017 |
| Source |
Sherwood Forest Hospitals NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Despite the best medical therapy many people with emphysema remain breathless and limited in
their daily activities. In emphysema the lungs do not empty properly when the person
breathes out. This "gas trapping" makes it harder to breathe. Endobronchial valve placement,
a treatment that stops air getting into the worst affected parts of the lung and so stops
them from trapping gas, improves lung function, breathlessness and exercise capacity in
selected patients with severe COPD (chronic obstructive airways disease, sometimes referred
to as emphysema). We want to see if people with less severe COPD who are very breathless can
benefit from the same treatment. The treatment involves placing small valves into the
airways using a fibre optic camera (a bronchoscopy). Bronchoscopy is a standard clinical
procedure carried out in our department.
Description:
Chronic Obstructive Pulmonary disease (COPD) is a common condition that affects millions of
adults worldwide with a prevalence and burden projected to increase in the coming decades.
This projected increase is explained by the ongoing exposure to cigarette smoke and other
COPD risk factors, particularly in the developing world, along with population demographic
changes and increasing life expectancy. The Global Burden of Disease Study predicted that by
2020 COPD will be ranked 5th behind ischaemic heart disease, depression, road traffic
accidents and cerebrovascular disease as a cause of disability-adjusted life years lost1.
The UK population prevalence of clinically significant COPD was estimated to be 1.7% for men
and 1.4% for women.
Emphysema can be a debilitating illness and can result in death. The damaged alveoli lose
their elasticity, and loss of structural elements leads to collapse of the terminal
bronchioles on expiration. This leads to gas trapping and hyperinflation. In severe cases,
alveolar walls can become destroyed creating bullae and collateral ventilation. Overinflated
areas of lung may compress adjacent lung tissue reducing perfusion and ventilation to
healthier tissue. Because the principal defect in emphysema is hyperinflation owing to
destruction of the elastic tissue of the lung, usual medical therapies targeted at
alleviating dyspnoea provide only limited benefit compared to patients with other forms of
COPD. Therefore, non-pharmacological methods of palliating dyspnoea in this patient group
have been developed, specifically lung volume reduction procedures.
Lung volume reduction improves function by the return of more normal respiratory muscle
shape and function, and also by improving the elastic recoil of the lung which in turn
increases the outward pull on the bronchioles. This reduces terminal bronchiole collapse and
improves expiratory airflow thereby reducing gas trapping. The decrease in the functional
residual capacity improves diaphragmatic and intercostal muscle function and reduces the
work of breathing. In carefully selected patients, lung volume reduction surgery (LVRS) has
been clearly shown to be effective at improving outcomes. It is, however, associated with
significant morbidity, a 5% mortality rate and a modest cost-benefit return. Unfortunately,
only a small minority of patients with emphysema are fit enough to undergo such major
surgeries, and therefore a variety of alternative less invasive techniques are being
developed to achieve lung volume reduction. These techniques include insertion of
unidirectional endobronchial valves (EBVs), lung volume reduction coils (RePneu©) to
internally compress hyperinflated emphysematous areas of lung, and the injection of
sclerosant material to induce scarring and fibrosis of the most damaged portions of lung.
Endobronchial valves work by allowing air to be expelled from the treated areas of lung
during expiration whilst preventing inspiratory airflow, with subsequent collapse of the
distal lung. This results in volume loss and allows reinflation of healthier lung tissue
with improved ventilation-perfusion matching. The Zephyr Valve (PulmonX, Redwood City, CA,
USA) allows exhaled air and secretions to be expelled through or around the valve but
prevent ventilation to the distal lung. It is implanted using a flexible bronchoscope under
conscious sedation as a day case procedure.
The Valves for Emphysema palliatioN Trial (VENT) is the largest randomised controlled trial
of valves published to date. Endobronchial valves were placed in the most diseased lobe to
achieve unilateral occlusion. This trial together with its European counterpart, EuroVENT,
demonstrated that significant improvements in lung function, exercise capacity, and quality
of life could be achieved.
Endobronchial valve insertion appears safe with the most commonly reported complications
being COPD exacerbation and small volume haemoptysis. Pneumothoraces are a more significant
complication but have only been reported at rates below 5% in these studies, although the
true rate in clinical practice with correctly chosen patients is likely to be nearer 20% (a
significant proportion of patients in the above trials did not have complete fissures, and
therefore would not be expected to have significant volume loss and hence pneumothorax).
Endobronchial valves are easily removed should the need arise.
The criteria for patient selection are currently very specific, limiting the procedure to a
small subgroup of patients with emphysema - specifically those with an FEV1 <45%. However,
the aim of EBV therapy is to reduce hyperinflation by deflating the most disease areas of
lung, resulting in improved respiratory mechanics and a greater inspiratory capacity, rather
than to correct airflow obstruction. In spite of significant reductions in the amount of
trapped gas, or residual volume (RV), in the lungs of patients treated with EBVs, some
patients see only modest improvements in functional outcomes such as the 6 minute walking
test. Airflow limitation alone causes reductions in exercise capacity, and it may be that
this limits treated patients even in the face of a reduction in the RV. Therefore, patients
with severe hyperinflation and limiting breathlessness (MRC dyspnoea score 3/5 or greater)
but relatively well preserved FEV1 might be expected to derive greater benefits in terms of
functional and patient reported outcomes as they will not be as limited by airflow
obstruction after the procedure.
