National Emphysema Treatment Trial (NETT)
Primary Purpose
Emphysema, Lung Diseases, Lung Diseases, Obstructive
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Lung volume reduction surgery
Sponsored by
About this trial
This is an interventional treatment trial for Emphysema
Eligibility Criteria
Men and women with end-stage emphysema.
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00000606
First Posted
October 27, 1999
Last Updated
April 13, 2016
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00000606
Brief Title
National Emphysema Treatment Trial (NETT)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2009
Overall Recruitment Status
Completed
Study Start Date
December 1996 (undefined)
Primary Completion Date
December 2005 (Actual)
Study Completion Date
December 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
Brief Summary
To evaluate the long term efficacy, morbidity and mortality associated with medical therapy with lung volume reduction surgery (LVRS) as compared to medical therapy alone and to define patient selection criteria. The trial, conducted in conjunction with a patient registry, is supported by the NHLBI, the Centers for Medicare and Medicaid Services (CMS), and the Agency for Healthcare Research and Quality (AHRQ).
Detailed Description
BACKGROUND:
LVRS is intended primarily for those patients whose chronic obstructive pulmonary disease (COPD) is predominantly emphysema. Emphysema is characterized anatomically "by abnormal, persistent enlargement of the airspaces distal to the terminal bronchioles, accompanied by the destruction of the airspace walls and without obvious fibrosis". The loss of the lung architecture leads to compressible peripheral airways that close at higher than normal lung volumes (early airway closure). The increased compliance and the air trapping from early closure leads to hyperinflation of the lung, over distention of the chest wall, a flattened, disadvantaged diaphragm, and ventilation-perfusion mismatch. In the 1950s and 1960s, Dr. Otto Brantigan theorized that surgical excision of multiple wedges of lung would reduce lung volumes, thereby restoring the outward elastic pull on the small airways and reduce airway obstruction. Dr. Brantigan reported that the surgical excision of lung tissue resulted in significant clinical improvement in some cases, but mortality was high. With little objective data and high mortality, the procedure did not gain widespread acceptance.
The experience that diaphragmatic and chest wall function could be restored in emphysema with lung transplantation renewed interest in Dr. Brantigan's work. Improvements in surgical technique have opened the possibility of performing surgical excisions of lung tissue. Recent reports on LVRS have shown improvements in FEV1, FVC, TLC, RV and dyspnea and quality of life assessments.
These reports generated enormous excitement among patients and their doctors. Many centers around the country started performing LVRS with the result that hundreds of patients had the procedure, despite the preliminary nature of the results, the lack of rigorous patient selection criteria and the lack of information on long term outcome. Basic questions remain such as which patient should have the surgery, what protocol should be followed, what physiological tests should be obtained, and what is the long term efficacy of the technique on morbidity, mortality, and quality of life. The mechanisms of benefit and the full cardiopulmonary consequences are unknown.
The concept for the trial originated in the NHLBI Workshop on Evaluation and Research in Lung Volume Reduction Surgery. The initiative was reviewed and approved at the May 1996 National Heart, Lung, and Blood Advisory Council meeting. The Requests for Proposals were released in June, 1996.
DESIGN NARRATIVE:
In the trial, 1218 eligible patients were randomized to receive either medical therapy (610) or medical therapy with LVRS(608). LVRS was performed by median sternotomy or video-assisted thorascopic surgery (VATS). Centers randomized their patients to either a) medical therapy alone versus medical therapy with LVRS by median sternotomy, b) medical therapy alone versus medical therapy with LVRS by VATS, or c) medical therapy alone versus medical therapy with LVRS by median sternotomy versus medical therapy with LVRS by bilateral VATS. Medical therapy included pulmonary rehabilitation and education. Direct comparisons of the two surgical techniques were possible only at the centers that performed both techniques. All arms included intensive pulmonary rehabilitation. The primary endpoints were survival and functional improvement as assessed by maximum workload. Secondary endpoints included morbidity, improvement in pulmonary function, quality of life and performance of activities of daily living. Follow-up exams, including history, physical exams, pulmonary function tests, exercise tests and quality of life assessments, occurred after pre-operative rehabilitation and six and twelve months after surgery and every twelve months thereafter. Recruitment ended July 31, 2002 and follow-up ended in December, 2002.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Emphysema, Lung Diseases, Lung Diseases, Obstructive, Chronic Obstructive Pulmonary Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
8. Arms, Groups, and Interventions
Intervention Type
Procedure
Intervention Name(s)
Lung volume reduction surgery
10. Eligibility
Sex
All
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Men and women with end-stage emphysema.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Piantadosi
Organizational Affiliation
Johns Hopkins University
12. IPD Sharing Statement
Citations:
PubMed Identifier
10469970
Citation
Rationale and design of the National Emphysema Treatment Trial (NETT): A prospective randomized trial of lung volume reduction surgery. J Thorac Cardiovasc Surg. 1999 Sep;118(3):518-28. doi: 10.1016/s0022-5223(99)70191-1. No abstract available.
Results Reference
background
PubMed Identifier
10593802
Citation
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. doi: 10.1378/chest.116.6.1750.
Results Reference
background
PubMed Identifier
11269488
Citation
Ramsey SD, Sullivan SD, Kaplan RM, Wood DE, Chiang YP, Wagner JL. Economic analysis of lung volume reduction surgery as part of the National Emphysema Treatment Trial. NETT Research Group. Ann Thorac Surg. 2001 Mar;71(3):995-1002. doi: 10.1016/s0003-4975(00)02283-9.
Results Reference
background
PubMed Identifier
11596594
Citation
Drazen JM. Surgery for emphysema--not for everyone. N Engl J Med. 2001 Oct 11;345(15):1126-8. doi: 10.1056/NEJM200110113451511. No abstract available.
Results Reference
background
PubMed Identifier
11596586
Citation
National Emphysema Treatment Trial Research Group; Fishman A, Fessler H, Martinez F, McKenna RJ Jr, Naunheim K, Piantadosi S, Weinmann G, Wise R. Patients at high risk of death after lung-volume-reduction surgery. N Engl J Med. 2001 Oct 11;345(15):1075-83. doi: 10.1056/NEJMoa11798.
Results Reference
background
PubMed Identifier
10680095
Citation
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. doi: 10.1097/00008483-200001000-00005.
Results Reference
background
PubMed Identifier
12153963
Citation
Scharf SM, Iqbal M, Keller C, Criner G, Lee S, Fessler HE; National Emphysema Treatment Trial (NETT) Group. Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med. 2002 Aug 1;166(3):314-22. doi: 10.1164/rccm.2107027.
Results Reference
background
PubMed Identifier
12759480
Citation
Ramsey SD, Berry K, Etzioni R, Kaplan RM, Sullivan SD, Wood DE; National Emphysema Treatment Trial Research Group. Cost effectiveness of lung-volume-reduction surgery for patients with severe emphysema. N Engl J Med. 2003 May 22;348(21):2092-102. doi: 10.1056/NEJMsa030448. Epub 2003 May 20.
Results Reference
background
PubMed Identifier
12759479
Citation
Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003 May 22;348(21):2059-73. doi: 10.1056/NEJMoa030287. Epub 2003 May 20.
Results Reference
background
PubMed Identifier
12759478
Citation
Ware JH. The National Emphysema Treatment Trial--how strong is the evidence? N Engl J Med. 2003 May 22;348(21):2055-6. doi: 10.1056/NEJMp030068. Epub 2003 May 20. No abstract available.
Results Reference
background
PubMed Identifier
12759481
Citation
Drazen JM, Epstein AM. Guidance concerning surgery for emphysema. N Engl J Med. 2003 May 22;348(21):2134-6. doi: 10.1056/NEJMe030058. Epub 2003 May 20. No abstract available.
Results Reference
background
PubMed Identifier
12615634
Citation
Sciurba F, Criner GJ, Lee SM, Mohsenifar Z, Shade D, Slivka W, Wise RA; National Emphysema Treatment Trial Research Group. Six-minute walk distance in chronic obstructive pulmonary disease: reproducibility and effect of walking course layout and length. Am J Respir Crit Care Med. 2003 Jun 1;167(11):1522-7. doi: 10.1164/rccm.200203-166OC. Epub 2003 Feb 20.
Results Reference
background
PubMed Identifier
15115992
Citation
McKenna RJ Jr, Benditt JO, DeCamp M, Deschamps C, Kaiser L, Lee SM, Mohsenifar Z, Piantadosi S, Ramsey S, Reilly J, Utz J; National Emphysema Treatment Trial Research Group. Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery. J Thorac Cardiovasc Surg. 2004 May;127(5):1350-60. doi: 10.1016/j.jtcvs.2003.11.025.
Results Reference
background
PubMed Identifier
15364757
Citation
Kaplan RM, Ries AL, Reilly J, Mohsenifar Z; National Emphysema Treatment Trial Research Group. Measurement of health-related quality of life in the national emphysema treatment trial. Chest. 2004 Sep;126(3):781-9. doi: 10.1378/chest.126.3.781.
Results Reference
background
PubMed Identifier
25340383
Citation
Kaplan RM, Sun Q, Ries AL. Quality of well-being outcomes in the National Emphysema Treatment Trial. Chest. 2015 Feb;147(2):377-387. doi: 10.1378/chest.14-0528.
Results Reference
derived
PubMed Identifier
25201722
Citation
Kaplan RM, Sun Q, Naunheim KS, Ries AL. Long-term follow-up of high-risk patients in the National Emphysema Treatment Trial. Ann Thorac Surg. 2014 Nov;98(5):1782-9. doi: 10.1016/j.athoracsur.2014.06.031. Epub 2014 Sep 4.
Results Reference
derived
PubMed Identifier
23828481
Citation
Argula RG, Strange C, Ramakrishnan V, Goldin J. Baseline regional perfusion impacts exercise response to endobronchial valve therapy in advanced pulmonary emphysema. Chest. 2013 Nov;144(5):1578-1586. doi: 10.1378/chest.12-2826.
Results Reference
derived
PubMed Identifier
20214820
Citation
Giardino ND, Curtis JL, Andrei AC, Fan VS, Benditt JO, Lyubkin M, Naunheim K, Criner G, Make B, Wise RA, Murray SK, Fishman AP, Sciurba FC, Liberzon I, Martinez FJ; NETT Research Group. Anxiety is associated with diminished exercise performance and quality of life in severe emphysema: a cross-sectional study. Respir Res. 2010 Mar 9;11(1):29. doi: 10.1186/1465-9921-11-29.
Results Reference
derived
PubMed Identifier
20018959
Citation
Hunninghake GM, Cho MH, Tesfaigzi Y, Soto-Quiros ME, Avila L, Lasky-Su J, Stidley C, Melen E, Soderhall C, Hallberg J, Kull I, Kere J, Svartengren M, Pershagen G, Wickman M, Lange C, Demeo DL, Hersh CP, Klanderman BJ, Raby BA, Sparrow D, Shapiro SD, Silverman EK, Litonjua AA, Weiss ST, Celedon JC. MMP12, lung function, and COPD in high-risk populations. N Engl J Med. 2009 Dec 31;361(27):2599-608. doi: 10.1056/NEJMoa0904006. Epub 2009 Dec 16.
Results Reference
derived
PubMed Identifier
19882497
Citation
Moy ML, Reilly JJ, Ries AL, Mosenifar Z, Kaplan RM, Lew R, Garshick E; National Emphysema Treatment Trial Research Group. Multivariate models of determinants of health-related quality of life in severe chronic obstructive pulmonary disease. J Rehabil Res Dev. 2009;46(5):643-54. doi: 10.1682/jrrd.2008.09.0127.
Results Reference
derived
PubMed Identifier
18641094
Citation
Drummond MB, Blackford AL, Benditt JO, Make BJ, Sciurba FC, McCormack MC, Martinez FJ, Fessler HE, Fishman AP, Wise RA; NETT Investigators. Continuous oxygen use in nonhypoxemic emphysema patients identifies a high-risk subset of patients: retrospective analysis of the National Emphysema Treatment Trial. Chest. 2008 Sep;134(3):497-506. doi: 10.1378/chest.08-0117. Epub 2008 Jul 18.
Results Reference
derived
PubMed Identifier
18535255
Citation
Martinez FJ, Han MK, Andrei AC, Wise R, Murray S, Curtis JL, Sternberg A, Criner G, Gay SE, Reilly J, Make B, Ries AL, Sciurba F, Weinmann G, Mosenifar Z, DeCamp M, Fishman AP, Celli BR; National Emphysema Treatment Trial Research Group. Longitudinal change in the BODE index predicts mortality in severe emphysema. Am J Respir Crit Care Med. 2008 Sep 1;178(5):491-9. doi: 10.1164/rccm.200709-1383OC. Epub 2008 Jun 5.
Results Reference
derived
PubMed Identifier
18535254
Citation
Snyder ML, Goss CH, Neradilek B, Polissar NL, Mosenifar Z, Wise RA, Fishman AP, Benditt JO; National Emphysema Treatment Trial Research Group. Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery. Am J Respir Crit Care Med. 2008 Aug 15;178(4):339-45. doi: 10.1164/rccm.200712-1826OC. Epub 2008 Jun 5.
Results Reference
derived
PubMed Identifier
17962632
Citation
Washko GR, Fan VS, Ramsey SD, Mohsenifar Z, Martinez F, Make BJ, Sciurba FC, Criner GJ, Minai O, Decamp MM, Reilly JJ; National Emphysema Treatment Trial Research Group. The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008 Jan 15;177(2):164-9. doi: 10.1164/rccm.200708-1194OC. Epub 2007 Oct 25.
Results Reference
derived
PubMed Identifier
17908710
Citation
Falk JA, Martin UJ, Scharf S, Criner GJ. Lung elastic recoil does not correlate with pulmonary hemodynamics in severe emphysema. Chest. 2007 Nov;132(5):1476-84. doi: 10.1378/chest.07-0041. Epub 2007 Oct 1.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
http://biolincc.nhlbi.nih.gov/studies/nett/
Available IPD/Information Identifier
NETT
Available IPD/Information Comments
NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://biolincc.nhlbi.nih.gov/studies/nett/
Available IPD/Information Type
Study Forms
Available IPD/Information URL
http://biolincc.nhlbi.nih.gov/studies/nett/
Learn more about this trial
National Emphysema Treatment Trial (NETT)
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