EmphysemaPhase 3NCT00000606
National Emphysema Treatment Trial (NETT)
A Phase 3 study testing Lung volume reduction surgery in people with Emphysema and Lung Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Emphysema, Lung Diseases, Lung Diseases, Obstructive
- What is being tested?
- Lung volume reduction surgery
- Type of treatment
- Surgery or procedure
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Dec 1996to Dec 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Men and women with end-stage emphysema.
About this study
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).
Read the 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.
- Conditions
- Emphysema, Lung Diseases, Lung Diseases, Obstructive, Chronic Obstructive Pulmonary Disease
- Being tested
- Lung volume reduction surgery
- Medical subject headings
- Emphysema, Lung Diseases, Lung Diseases, Obstructive, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lung volume reduction surgeryProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startDec 1996
- Primary completionDec 2005
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for EmphysemaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Steven Piantadosi, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000606
- Sponsor's protocol ID
- 218
- Status last verified
- Apr 2009
- First submitted
- 27 Oct 1999
- Last updated
- 14 Apr 2016
- Results posted
- No
Publications
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.
PubMed 10469970Rationale 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.
PubMed 10593802Ramsey 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.
PubMed 11269488Drazen 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.
PubMed 11596594National 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.
PubMed 11596586Rationale 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.
PubMed 10680095Scharf 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.
PubMed 12153963Ramsey 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.
PubMed 12759480Fishman 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.
PubMed 12759479Ware 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.
PubMed 12759478Drazen 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.
PubMed 12759481Sciurba 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.
PubMed 12615634McKenna 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.
PubMed 15115992Kaplan 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.
PubMed 15364757Kaplan 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.
PubMed 25340383
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- National Emphysema Treatment Trial (NETT)
- ClinicalTrials.gov ID
- NCT00000606
- Acronym / sponsor ID
- 218
- Conditions
- Emphysema, Lung Diseases, Lung Diseases, Obstructive, Chronic Obstructive Pulmonary Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Dec 1996
- Primary completion
- Dec 2005 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 28 Oct 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lung volume reduction surgery | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2016.
- Background: PubMed 10469970Rationale 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.
- Background: PubMed 10593802Rationale 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.
- Background: PubMed 11269488Ramsey 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.
- Background: PubMed 11596594Drazen 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.
- Background: PubMed 11596586National 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.
- Background: PubMed 10680095Rationale 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.
- Background: PubMed 12153963Scharf 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.
- Background: PubMed 12759480Ramsey 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.
- Background: PubMed 12759479Fishman 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.
- Background: PubMed 12759478Ware 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.
- Background: PubMed 12759481Drazen 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.
- Background: PubMed 12615634Sciurba 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Piantadosi
Johns Hopkins University
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lung volume reduction surgery in people with Emphysema and Lung Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000606, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2016.