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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Aortic Aneurysm

Intervention / Treatment
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* Procedure: Endovascular Repair
* Procedure: Standard Open Repair


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Standard Open Repair of Abdominal Aortic Aneurysm | Procedure: Standard Open Repair<br>* Standard Open Repair<br>|
| Active Comparator: Arm 2<br>Endovascular Repair of Abdominal Aortic Aneurysm | Procedure: Endovascular Repair<br>* Endovascular Repair<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abdominal, Aortic Aneurysm, cost of AAA repair, Endovascular Repair, Grafts, Long-term survival, secondary outcomes