This is the first time that researchers have identified scientifically based selection criteria for patients seeking LVRS as a potential treatment for advanced emphysema. As a result of the findings, patients with these high-risk characteristics are no longer being enrolled in NETT; however, the study will continue to recruit other eligible patients until its scheduled completion in 2002.
"This is exactly the kind of insight we hope to gain from NETT," said Dr. Claude Lenfant, director of the National Heart, Lung, and Blood Institute (NHLBI), the primary sponsor of the study. "Identifying which patients should not undergo this surgery is a key goal of this study. We expect the final results of NETT will guide us further in determining if and when this procedure should be used to treat emphysema."
The findings will be posted on the New England Journal of Medicine (NEJM) Web site (www.nejm.org) on August 14. Because of the importance of the results, NEJM editors agreed to expedite their review of the findings and to publish them on their Internet site prior to printing the investigators' report within the next few months.
The largest study of its kind, NETT compares the safety and effectiveness of LVRS with medical treatment in patients with advanced emphysema. The study also aims to define better who benefits from LVRS and who is at excessive risk of complications or death from the procedure. More than 1,000 participants at 17 clinical sites have enrolled in NETT since 1997.
In emphysema, the fine architecture of the lung is destroyed, leading to large holes in the lung, obstruction of the airways, trapping of air, and difficulty exchanging oxygen. Current medical treatments include supportive measures such as medications, exercise rehabilitation, and nutritional supplementation.
LVRS is an unproven modality to ease symptoms associated with advanced emphysema and to improve overall lung function. The procedure is believed by some to improve the ability to move air in and out of the lungs by surgically removing as much as one-third of each lung, targeting the most damaged regions, with the expectation that the remaining lung will have better air exchange. NETT was developed in response to concerns from both the medical community and from the Center for Medicare and Medicaid Services (formerly the Health Care Financing Administration) about the risks and benefits of LVRS compared to medical treatment for advanced emphysema.
During its quarterly review of the study data in May 2001, the NETT Data and Safety Monitoring Board (DSMB) found that a subgroup of participants undergoing the procedure had a 30-day post-surgery death rate considered unacceptable based on the study's safety monitoring guidelines. The DSMB is a designated group of experts who are unaffiliated with NETT and who are responsible for overseeing participants' safety and outcomes data; in addition, the NETT DSMB is charged with identifying subgroups of patients who may benefit from or be at high risk of dying from LVRS.
Based on its analysis, the DSMB recommended that the study protocol be revised to no longer enroll patients that meet specific criteria. NHLBI and the NETT investigators agreed with the DSMB recommendation and modified the patient eligibility criteria immediately. Within the following weeks, NHLBI notified the leading pulmonary professional societies, and the NETT investigators notified the participants and their families.
As a result of this decision, NETT is no longer enrolling patients with severe obstruction in the lung as measured by a forced expiratory volume in one second less than or equal to 20 percent of predicted, plus one of the following characteristics: severe loss of lung surface area as measured by a diffusing capacity of less than 20 percent predicted or homogeneous damage to the lung, that is, disease is evenly distributed throughout the lung, rather than being confined to certain areas.
Of the 1,033 current participants, 140 (14 percent) met the above high-risk criteria, 69 of whom underwent surgery as part of the trial. These patients had a 16 percent 30-day mortality rate. In contrast, no deaths were reported in the medical treatment group 30 days following the start of medical treatment.
Furthermore, compared to similar participants who received only medical treatment, high-risk participants who survived the surgery were found to have only slightly improved functional outcomes and quality-of-life scores six months after enrolling in the study.
In addition to NHLBI, NETT is supported by the Center for Medicare and Medicaid Services, which supports clinical services for the study, and the Agency for Healthcare Research and Quality.
Emphysema is a disabling condition that affects approximately 2 million Americans, most of them over age 50. Typically caused by cigarettes, the disabling and deadly condition costs more than $2.5 billion in annual health care expenses and kills more than 16,000 people in the U.S. each year.
NHLBI is part of the National Institutes of Health in Bethesda, Maryland.
NHLBI press releases, resources for professionals and consumers, and other materials are online at www.nhlbi.nih.gov.
Journal
New England Journal of Medicine