Standard Open Surgery Versus Endovascular Repair of Abdominal Aortic Aneurysm (AAA)

Aortic Aneurysm Clinical Trial

— OVER  

Official title:

CSP #498 - Open Versus Endovascular Repair (OVER) Trial for Abdominal Aortic Aneurysms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094575
• Other study ID #: 498
• Status: Completed
• Phase: Phase 4
• First received: October 20, 2004
• Last updated: February 8, 2016
• Start date: October 2002
• Est. completion date: April 2012

Study information

• Verified date: February 2016
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

A multi-center, randomized clinical trial that will compare endovascular repair with standard open surgery in the repair of abdominal aortic aneurysms (AAA). Long and short-term results as well as the cost and quality of life associated with these two strategies for AAA repair will be compared.

Description:

Primary Hypothesis: All-cause mortality will differ by 25% between Endovascular repair (EVR) and Open repair. Secondary Hypotheses: Procedure failure, short term (12-month) major morbidity, number of hospital days, health-related quality of life and other procedure-related abnormalities will differ between the two AAA repair strategies. Primary Outcomes: All-cause mortality. Interventions: Patients will be randomized to one of these repair strategies for the elective treatment of AAA: (a) Open repair or (b) Endovascular repair (using FDA-approved devices). Study Abstract: Aortic aneurysm is the tenth leading cause of death in older men; AAA accounts for the majority of these deaths (about 10,000 deaths per year in the United States). Since one in 22 Veterans over the age of 50 have AAA and one in 200 have AAA with diameter greater or equal to 5.0 cm (making them candidates for elective repair), AAA is a major disease in the VA population. Questions about the relative safety and effectiveness of FDA approved EVR devices have been raised and remain unanswered. To answer these questions, this multi-center, randomized clinical trial comparing EVR with standard open surgery is proposed. Patients for whom elective repair of AAA is indicated and who are suitable candidates for both open repair and EVR will be eligible for the study. The anticipated duration of the study is 9 years with a proposed sample size of 900 patients. The first planning meeting took place on March 9-10, 2000 and the second planning meeting took place on November 6-7, 2000. The OVER protocol was submitted and reviewed by CSEC on May 10, 2001 and approved. The kickoff was June 12, 2002. The first DSMB meeting took place January 6, 2003. First annual meeting was held September 30, 2003; second DSMB meeting took place September 29, 2003. Third DSMB meeting held on April 19, 2004; second annual meeting was held on June 29, 2004. Fourth DSMB meeting was held on December 6, 2004; third annual meeting was held on March 15, 2005. The fifth DSMB meeting was held on July 19, 2005 and the fourth annual meeting was held March 21, 2006. The sixth DSMB meeting was held September 12, 2005. The seventh DSMB meeting was held on March 6, 2006. The eighth DSMB meeting was held on November 6, 2006. At its November 6, 2006 meeting, the DSMB discussed and approved unblinding of the study chair to prepare the short-term follow-up paper as specified in the study protocol. Initially the protocol called for this analysis to include one-year follow-up data. After discussions with the Trial Leadership, the DSMB approved use of two year follow-up data (reflected in DSMB minutes finalized February 20, 2007). This recommendation was subsequently approved by CSP in March 2007. The short-term outcomes manuscript was published in JAMA on October 14, 2009. The ninth DSMB meeting was held on May 14, 2007 and the fifth annual meeting was held on June 6, 2007. The tenth DSMB meeting was held on April 7, 2008. The eleventh DMC (name change only from DSMB to DMC) was held on June 22, 2009. The twelfth DMC meeting was held on May 24, 2010. A Site Investigator meeting was held in Boston, MA on June 9, 2010. The thirteenth DMC meeting was held on June 3, 2011 and a study close-out meeting was held on June 15, 2011 in Chicago, IL. The study's patient follow-up phase ended October 15, 2011.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 881
• Est. completion date: April 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• AAA with a maximum external diameter in any plane greater than or equal to 5 cm.

• An iliac aneurysm (associated with an AAA) with a maximum external diameter in any plane greater than or equal to 3 cm.

• AAA greater than or equal to 4.5 cm and the AAA has increased by greater than or equal to 0.7 cm in diameter in 6 months.

• An AAA greater than or equal to 4.5 cm and the AAA has increased by greater than or equal to 1 cm in diameter in 12 months.

• An AAA greater than or equal to 4.5 cm and the AAA is saccular (i.e., a portion of the circumference of the aorta at the level of the aneurysm is considered normal based on CT scan or MRI).

• An AAA greater than or equal to 4.5 cm and the AAA is associated with distal embolism.

• as measured from two imaging studies (ultrasound CT scan or MRI) within the appropriate interval, the later one within 6 months of randomization.

Exclusion Criteria:

• Patient has had a previous AAA repair procedure

• Evidence of AAA rupture by imaging test

• AAA is not elective (i.e., urgent or emergent operation, usually due to suspected rupture)

• Likelihood of poor compliance to the protocol

• Patient refused randomization

• Physician refused randomization

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal

Intervention

Procedure:
• Endovascular Repair
Endovascular Repair
• Standard Open Repair
Standard Open Repair

Locations

Country	Name	City	State
United States	New Mexico VA Health Care System, Albuquerque	Albuquerque	New Mexico
United States	VA Maryland Health Care System, Baltimore	Baltimore	Maryland
United States	VA Medical Center, Birmingham	Birmingham	Alabama
United States	VA Boston Healthcare System, Brockton Campus	Brockton	Massachusetts
United States	VA Western New York Healthcare System at Buffalo	Buffalo	New York
United States	Jesse Brown VAMC (WestSide Division)	Chicago	Illinois
United States	VA Medical Center, Cincinnati	Cincinnati	Ohio
United States	VA Medical Center, Cleveland	Cleveland	Ohio
United States	VA North Texas Health Care System, Dallas	Dallas	Texas
United States	Atlanta VA Medical and Rehab Center, Decatur	Decatur	Georgia
United States	VA Eastern Colorado Health Care System, Denver	Denver	Colorado
United States	John D. Dingell VA Medical Center, Detroit	Detroit	Michigan
United States	VA Medical Center, Durham	Durham	North Carolina
United States	VA New Jersey Health Care System, East Orange	East Orange	New Jersey
United States	North Florida/South Georgia Veterans Health System	Gainesville	Florida
United States	Edward Hines, Jr. VA Hospital	Hines	Illinois
United States	Michael E. DeBakey VA Medical Center (152)	Houston	Texas
United States	Richard Roudebush VA Medical Center, Indianapolis	Indianapolis	Indiana
United States	VA Medical Center, Iowa City	Iowa City	Iowa
United States	VA Medical Center, Lexington	Lexington	Kentucky
United States	VA Medical Center, Loma Linda	Loma Linda	California
United States	VA Medical Center, Long Beach	Long Beach	California
United States	Wlliam S. Middleton Memorial Veterans Hospital, Madison	Madison	Wisconsin
United States	VA Medical Center, Memphis	Memphis	Tennessee
United States	Zablocki VA Medical Center, Milwaukee	Milwaukee	Wisconsin
United States	Minneapolis VA Health Care System	Minneapolis	Minnesota
United States	New York Harbor HCS	New York	New York
United States	Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock	No. Little Rock	Arkansas
United States	VA Medical Center, Omaha	Omaha	Nebraska
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	VA Medical Center, Philadelphia	Philadelphia	Pennsylvania
United States	VA Pittsburgh Health Care System	Pittsburgh	Pennsylvania
United States	VA Medical Center, Portland	Portland	Oregon
United States	VA Salt Lake City Health Care System, Salt Lake City	Salt Lake City	Utah
United States	VA San Diego Healthcare System, San Diego	San Diego	California
United States	VA Medical Center, San Francisco	San Francisco	California
United States	VA Puget Sound Health Care System, Seattle	Seattle	Washington
United States	James A. Haley Veterans Hospital, Tampa	Tampa	Florida
United States	Southern Arizona VA Health Care System, Tucson	Tucson	Arizona
United States	VA Medical Center, DC	Washington	District of Columbia
United States	VA Connecticut Health Care System (West Haven)	West Haven	Connecticut
United States	VA Greater Los Angeles Healthcare System, West LA	West Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (10)

Findeiss LK. Comparing endovascular and open repair of abdominal aortic aneurysm. JAMA. 2010 Feb 10;303(6):514; author reply 514. doi: 10.1001/jama.2010.88. — View Citation

Lal BK, Zhou W, Li Z, Kyriakides T, Matsumura J, Lederle FA, Freischlag J; OVER Veterans Affairs Cooperative Study Group. Predictors and outcomes of endoleaks in the Veterans Affairs Open Versus Endovascular Repair (OVER) Trial of Abdominal Aortic Aneurys — View Citation

Lederle FA, Freischlag JA, Kyriakides TC, Matsumura JS, Padberg FT Jr, Kohler TR, Kougias P, Jean-Claude JM, Cikrit DF, Swanson KM; OVER Veterans Affairs Cooperative Study Group. Long-term comparison of endovascular and open repair of abdominal aortic ane — View Citation

Lederle FA, Freischlag JA, Kyriakides TC, Padberg FT Jr, Matsumura JS, Kohler TR, Lin PH, Jean-Claude JM, Cikrit DF, Swanson KM, Peduzzi PN; Open Versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group. Outcomes following endovascular v — View Citation

Lederle FA, Stroupe KT; Open Versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group. Cost-effectiveness at two years in the VA Open Versus Endovascular Repair Trial. Eur J Vasc Endovasc Surg. 2012 Dec;44(6):543-8. doi: 10.1016/j.ejvs.2 — View Citation

Lederle FA. Abdominal aortic aneurysm: still no pill. Ann Intern Med. 2013 Dec 17;159(12):852-3. — View Citation

Lederle FA. The rise and fall of abdominal aortic aneurysm. Circulation. 2011 Sep 6;124(10):1097-9. doi: 10.1161/CIRCULATIONAHA.111.052365. — View Citation

Lederle FA. The strange relationship between diabetes and abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2012 Mar;43(3):254-6. doi: 10.1016/j.ejvs.2011.12.026. Epub 2012 Jan 9. — View Citation

Lederle FA. Vascular disease: is AAA screening worth the cost? Nat Rev Cardiol. 2009 Oct;6(10):616-8. doi: 10.1038/nrcardio.2009.161. — View Citation

Stroupe KT, Lederle FA, Matsumura JS, Kyriakides TC, Jonk YC, Ge L, Freischlag JA; Open Versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group. Cost-effectiveness of open versus endovascular repair of abdominal aortic aneurysm in the O — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality	Participants vital status was assessed from randomization to end of study follow-up [10/15/2011] or death [whichever occurred first].	Participants were followed for the duration of the study, up to 9 years	No
Secondary	Secondary Therapeutic Procedures	This outcome includes any procedure that resulted directly or indirectly from the initial procedure and that required a separate trip to the procedure suite (with each trip to the procedure suite counting as one secondary procedure), including any unplanned surgical procedures within 30 days after the initial procedure and any additional aortoiliac procedures at any time.	Participants were followed for the duration of the study, up to 9 years	No
Secondary	SF-36 Mental Component Score (MCS)	Change (over time) since baseline in Mental Component Score of SF-36. The MCS Score ranges from 0-100 with higher scores indicating better health. Longitudinal mixed-effects model, adjusted for baseline values, was used to compare the two study arms. Treatment effect and change in quality-of-life measures over time were assessed in repeated measures models (with unstructured covariance) with the assigned repair method and baseline measurements used as covariates.; Least-squares mean changes from baseline were calculated at each time point; the reported overall least squares mean is calculated over all time points.	Outcome was assessed at 6 months and then yearly, up to 9 years	No
Secondary	SF-36 Physical Component Score (PCS)	Change (over time) since baseline in Physical Component Score of SF-36. The PCS Score ranges from 0-100 with higher scores indicating better health Longitudinal mixed-effects model, adjusted for baseline values, was used to compare the two study arms. Treatment effect and change in quality-of-life measures over time were assessed in repeated measures models (with unstructured covariance) with the assigned repair method and baseline measurements used as covariates.; Least-squares mean changes from baseline were calculated at each time point; the reported overall least squares mean is calculated over all time points.	Outcome was assessed at 6 months and yearly thereafter, up to 9 years	No
Secondary	SF-36 Physical Component Deaths Included Score (PCTD)	Change (over time) since baseline in Physical Component Deaths included Score of SF-36.; The PCTD Score ranges from 0-100 with higher scores indicating better health. Longitudinal mixed-effects model, adjusted for baseline values, was used to compare the two study arms. Treatment effect and change in quality-of-life measures over time were assessed in repeated measures models (with unstructured covariance) with the assigned repair method and baseline measurements used as covariates.; Least-squares mean changes from baseline were calculated at each time point; the reported overall least squares mean is calculated over all time points.	Outcome was assessed at 6 months and yearly thereafter, up to 9 years	No
Secondary	European Quality of Life-5 Dimension (EQ-5D) Index Score	Change (over time) since baseline in EQ-5D. The EQ-5D Index Score ('thermometer scale') ranges from 0 (worst health status) to 100 (best health status). Since this outcome captures change since baseline, values could be below 0.; Longitudinal mixed-effects model, adjusted for baseline values, was used to compare the two study arms. Treatment effect and change in quality-of-life measures over time were assessed in repeated measures models (with unstructured covariance) with the assigned repair method and baseline measurements used as covariates.; Least-squares mean changes from baseline were calculated at each time point; the reported overall least squares mean is calculated over all time points.	Outcome was assessed at 6 months and yearly thereafter, up to 9 years	No
Secondary	European Quality of Life-5 Dimension (EQ-5D) Visual Analog Scale	Change (over time) since baseline in EQ-5D Visual Analog Scale. The EQ-5D Visual Analog Scale ranges from 0 (death) to 1 (perfect health). Longitudinal mixed-effects model, adjusted for baseline values, was used to compare the two study arms. Treatment effect and change in quality-of-life measures over time were assessed in repeated measures models (with unstructured covariance) with the assigned repair method and baseline measurements used as covariates.; Least-squares mean changes from baseline were calculated at each time point; the reported overall least squares mean is calculated over all time points.	Outcome was assessed at 6 months and yearly thereafter, up to 9 years	No
Secondary	International Index of Erectile Function (IIEF-5)	Change (over time) since baseline in IIEF-5. The IIEF-5 Score ranges from 5-25 with higher scores indicating better erectile function.; Longitudinal mixed-effects model, adjusted for baseline values, was used to compare the two study arms. Treatment effect and change in quality-of-life measures over time were assessed in repeated measures models (with unstructured covariance) with the assigned repair method and baseline measurements used as covariates.; Least-squares mean changes from baseline were calculated at each time point; the reported overall least squares mean is calculated over all time points.	Outcome was assessed at 6 months and yearly thereafter, up to 9 years	No