The National Emphysema Treatment Trial (NETT) was the first multi-center clinical trial designed to determine the role, safety and effectiveness of bilateral lung volume reduction surgery (LVRS) in the treatment of emphysema. Concluded in 2002, it was supported by the National Heart, Lung and Blood Institute (NHLBI), the Health Care Financing Administration (HCFA) and the Agency for Health Care Policy and Research (AHCPR).
Emphysema is a chronic lung condition that is a major cause of death and disability in the U.S. If LVRS is found to be beneficial, then a secondary objective will be to develop criteria for identifying patients who are likely to benefit from the procedure.
In patients with emphysema, the walls between the tiny air sacs in the lungs are damaged. While healthy lungs expand with each inhalation and collapse with each exhalation, lungs damaged by emphysema gradually lose their elasticity, becoming floppy and over-expanded, like a spent rubber band. The airways, normally held open by the elastic pull of the lungs, also become floppy and collapse on exhalation. As a result, patients with emphysema have increasing difficulty moving air in and out of their lungs.
LVRS reduces the size of the lungs. The theory underlying the surgery is that reducing the lung size will pull open the airways and allow the breathing muscles to return to a more normal and comfortable position, making breathing easier.
LVRS has been proposed as a new treatment that can improve quality of life for people with end-stage emphysema, but many questions about the procedure are unanswered. For example:
- What are the benefits and the risks compared with good medical therapy alone?
- How long do any benefits last?
- Does the surgery benefit some patients more than others?
The NHLBI of the National Institutes of Health undertook NETT to provide definitive answers to these important questions. HCFA, which oversees the Medicare program and cosponsored NETT, used the data from the study to determine whether Medicare should provide reimbursement for LVRS. The NETT findings have led to the announcement that Medicare will soon cover the cost of the procedure. Initially, to receive this coverage, patients must undergo LVRS at one of the 17 medical
centers that participated in NETT.
LVRS was first used to treat emphysema in the 1950s. Although some patients seemed to improve following the surgery, high mortality and morbidity associated with LVRS prevented its widespread use. In the early 1990s, some physicians began using the procedure again. Early reported successes led to its rapid spread, despite the lack of data on its long-term benefits, risks and costs.
To examine the safety and effectiveness of LVRS, the NHLBI convened a workshop of experts in treating emphysema in 1995. The workshop participants reviewed the available data and unanimously agreed that a systematic evaluation of patient selection criteria and long-term outcomes should be undertaken before the surgery became widely practiced.
An independent assessment of LVRS performed for HCFA concluded that the current data on the risks and benefits of LVRS were too inconclusive to justify unrestricted Medicare reimbursement for the surgery. However, because some patients appeared to benefit from the procedure, the Center for Health Care Technology of the AHCPR, which performed the assessment, advised HCFA that a trial evaluating the effectiveness of the surgery was essential.
As a result, the NHLBI and HCFA announced in April 1996 that they would conduct a scientific study of LVRS to evaluate the safety and effectiveness of the current best available medical treatment alone and in conjunction with LVRS. In late 1996, the participating clinical centers and a coordinating center were announced. Patient screening for entry into the study began in the fall of 1997. Completed in
2002, the study showed that patients
with upper lobe emphysema had better
pulmonary function and exercise
tolerance after LVRS than after medical
(nonsurgical) treatment. For patients with
upper lobe emphysema and poor exercise
tolerance, the survival rate was better after
LVRS than after medical treatment.
Since the centers were selected, the NETT investigators and HCFA have continued to review data on the effectiveness of LVRS, but they have found insufficient follow-up data on too many of the patients to permit definitive conclusions. Of the 1,741 LVRS cases performed at the NETT centers prior to the study, the investigators found that only 25% had sufficient follow-up data to determine outcome. With information missing on 75% of the patients, it is not possible to draw conclusions about outcomes, especially since patients who do better following surgery are more likely to return for follow-up than sicker patients.
While Medicare has complete data on 711 patients who underwent LVRS between October 1995 and January 1996, these data contrast sharply with those in the published literature, which reports successes in selected cases and low mortality. The Medicare data shows that 26% of the patients had died by January 1997, 40% had been re-hospitalized (averaging 2.1 admissions and 30 hospital days), and 16% required long-term inpatient care. Due to the absence of a control group, however, it is not known whether these outcomes can be attributed to the surgery or to the natural history of the underlying disease.
The trial is designed to include about 4,500 patients and to take up to five years to complete. The trial could be ended early if one of the quarterly data reviews shows clear risk or benefit for one of the treatments.
People who are interested in participating in the trial should ask their doctors to send their medical history, a chest X-ray and results of spirometry and EKG tests to the NETT center of their choice. Based on this preliminary information, the center will determine whether further screening is warranted. If so, the patient will be asked to undergo an evaluation to establish whether he or she meets the eligibility criteria and to provide baseline data.
Once enrolled in the study, consenting patients will complete a six- to 10-week rehabilitation program in which they will receive medicines and oxygen as needed and participate in a program of exercise and breathing methods. These currently are the best known medical treatments for emphysema.
After successful completion of this rehabilitation program, consenting patients will be randomly assigned, either to continue this treatment or to have lung volume reduction surgery in addition to continued medical treatment.
For this trial, surgery will be performed on both lungs, either by insertion of a tube through the chest wall (bilateral video-assisted thorascopy) or by an incision through the center of the breastbone (median sternotomy). In centers with experience in both techniques, patients receiving surgery will be randomly assigned to one of the surgical methods.
Participants in NETT must have a diagnosis of emphysema that substantially reduces their ability to function. They must meet certain pulmonary function and CT scan requirements and be approved for surgery by a cardiologist, a pulmonologist and a thoracic surgeon.
However, they cannot participate if they have:
- Smoked tobacco within the last four months
- Unstable angina or cardiac arrhythmia
- Had a heart attack within the past six months
- Had certain selected thoracic or cardiac surgeries
- Another disease that may interfere with trial participation or reduce survival
Medicare recipients enrolled in NETT will receive coverage for all services integral to the study that are permitted under Medicare law. Expenses not normally covered by Medicare, such as the costs of oral medications, will be the responsibility of the patient or possibly any additional insurance the patient may have. Patients may be responsible for deductibles and co-payments required by Medicare and other insurers.
Private insurers also are participating in NETT, so people interested in participating in the study should check with their insurers about coverage of services.
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- Rationale and design of the National Emphysema Treatment Trial. A prospective randomized trial of lung volume reduction surgery. The national emphysema treatment trial research group. J Cardiopulm Rehabil. 2000 Jan; 20(1):24-36.
- Rationale and design of the National Emphysema Treatment Trial: A prospective randomized trial of lung volume reduction surgery. The National Emphysema Treatment Trial Research Group. Chest. 1999 Dec; 116(6):1750-61.
