Clinical trial NCT00094575: Standard Open Surgery Versus Endovascular Repair of Abdominal Aortic Aneurysm (AAA)
Official title: CSP #498 - Open Versus Endovascular Repair (OVER) Trial for Abdominal Aortic Aneurysms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aortic Aneurysm
Keywords: Abdominal
Aortic Aneurysm
cost of AAA repair
Endovascular Repair
Grafts
Long-term survival
secondary outcomes
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2004-10-21
Enrollment: 881
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause Mortality
timeFrame: Participants were followed for the duration of the study, up to 9 years
Secondary outcomes:
measure: Secondary Therapeutic Procedures
timeFrame: Participants were followed for the duration of the study, up to 9 years
measure: SF-36 Mental Component Score (MCS)
timeFrame: Outcome was assessed at 6 months and then yearly, up to 9 years
measure: SF-36 Physical Component Score (PCS)
timeFrame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
measure: SF-36 Physical Component Deaths Included Score (PCTD)
timeFrame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
measure: European Quality of Life-5 Dimension (EQ-5D) Index Score
timeFrame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
measure: European Quality of Life-5 Dimension (EQ-5D) Visual Analog Scale
timeFrame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
measure: International Index of Erectile Function (IIEF-5)
timeFrame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: VA Medical Center, Birmingham
state: Alabama
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System, Tucson
state: Arizona
city: No. Little Rock
country: United States
facility: Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
state: Arkansas
city: Loma Linda
country: United States
facility: VA Medical Center, Loma Linda
state: California
city: Long Beach
country: United States
facility: VA Medical Center, Long Beach
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System, San Diego
state: California
city: San Francisco
country: United States
facility: VA Medical Center, San Francisco
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West LA
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Health Care System, Denver
state: Colorado
city: West Haven
country: United States
facility: VA Connecticut Health Care System (West Haven)
state: Connecticut
city: Washington
country: United States
facility: VA Medical Center, DC
state: District of Columbia
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital, Tampa
state: Florida
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur
state: Georgia
city: Chicago
country: United States
facility: Jesse Brown VAMC (WestSide Division)
state: Illinois
city: Hines
country: United States
facility: Edward Hines, Jr. VA Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Richard Roudebush VA Medical Center, Indianapolis
state: Indiana
city: Iowa City
country: United States
facility: VA Medical Center, Iowa City
state: Iowa
city: Lexington
country: United States
facility: VA Medical Center, Lexington
state: Kentucky
city: Baltimore
country: United States
facility: VA Maryland Health Care System, Baltimore
state: Maryland
city: Brockton
country: United States
facility: VA Boston Healthcare System, Brockton Campus
state: Massachusetts
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center, Detroit
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System
state: Minnesota
city: Omaha
country: United States
facility: VA Medical Center, Omaha
state: Nebraska
city: East Orange
country: United States
facility: VA New Jersey Health Care System, East Orange
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico VA Health Care System, Albuquerque
state: New Mexico
city: Buffalo
country: United States
facility: VA Western New York Healthcare System at Buffalo
state: New York
city: New York
country: United States
facility: New York Harbor HCS
state: New York
city: Durham
country: United States
facility: VA Medical Center, Durham
state: North Carolina
city: Cincinnati
country: United States
facility: VA Medical Center, Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: VA Medical Center, Cleveland
state: Ohio
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
city: Philadelphia
country: United States
facility: VA Medical Center, Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Health Care System
state: Pennsylvania
city: Memphis
country: United States
facility: VA Medical Center, Memphis
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System, Dallas
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center (152)
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City
state: Utah
city: Seattle
country: United States
facility: VA Puget Sound Health Care System, Seattle
state: Washington
city: Madison
country: United States
facility: Wlliam S. Middleton Memorial Veterans Hospital, Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Zablocki VA Medical Center, Milwaukee
state: Wisconsin
Study officials:
affiliation: Minneapolis Veterans Affairs Medical Center
name: Frank A. Lederle, MD
role: STUDY_CHAIR
References:
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. No abstract available.
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 vs open repair of abdominal aortic aneurysm: a randomized trial. JAMA. 2009 Oct 14;302(14):1535-42. doi: 10.1001/jama.2009.1426.
citation: Lederle FA, Freischlag JA, Kyriakides TC. Comparing endovascular and open repair of abdominal aortic aneurysm - [Author Reply To Editorial]. Journal of The American Medical Association. 2010 Feb 10; 303(6):514.
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. No abstract available.
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.
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 OVER trial. J Vasc Surg. 2012 Oct;56(4):901-9.e2. doi: 10.1016/j.jvs.2012.01.086. Epub 2012 May 27.
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 aneurysm. N Engl J Med. 2012 Nov 22;367(21):1988-97. doi: 10.1056/NEJMoa1207481.
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.2012.10.002. Epub 2012 Oct 30.
citation: Lederle FA. Abdominal aortic aneurysm: still no pill. Ann Intern Med. 2013 Dec 17;159(12):852-3. doi: 10.7326/0003-4819-159-12-201312170-00012. No abstract available.
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 Aneurysms. J Vasc Surg. 2015 Dec;62(6):1394-404. doi: 10.1016/j.jvs.2015.02.003.
citation: Lederle FA, Kyriakides TC, Stroupe KT, Freischlag JA, Padberg FT Jr, Matsumura JS, Huo Z, Johnson GR; OVER Veterans Affairs Cooperative Study Group. Open versus Endovascular Repair of Abdominal Aortic Aneurysm. N Engl J Med. 2019 May 30;380(22):2126-2135. doi: 10.1056/NEJMoa1715955.
citation: Powell JT, Sweeting MJ, Ulug P, Blankensteijn JD, Lederle FA, Becquemin JP, Greenhalgh RM; EVAR-1, DREAM, OVER and ACE Trialists. Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years. Br J Surg. 2017 Feb;104(3):166-178. doi: 10.1002/bjs.10430.
citation: Lederle FA, Stroupe KT, Kyriakides TC, Ge L, Freischlag JA; Open vs Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group. Long-term Cost-effectiveness in the Veterans Affairs Open vs Endovascular Repair Study of Aortic Abdominal Aneurysm: A Randomized Clinical Trial. JAMA Surg. 2016 Dec 1;151(12):1139-1144. doi: 10.1001/jamasurg.2016.2783.
citation: Myers SA, Applequist BC, Huisinga JM, Pipinos II, Johanning JM. Gait kinematics and kinetics are affected more by peripheral arterial disease than by age. J Rehabil Res Dev. 2016;53(2):229-38. doi: 10.1682/JRRD.2015.02.0027.
citation: Matsumura JS, Stroupe KT, Lederle FA, Kyriakides TC, Ge L, Freischlag JA; Open Versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group. Costs of repair of abdominal aortic aneurysm with different devices in a multicenter randomized trial. J Vasc Surg. 2015 Jan;61(1):59-65. doi: 10.1016/j.jvs.2014.08.003. Epub 2014 Sep 16.