Aortic Aneurysm
Conditions
Keywords
Abdominal, Aortic Aneurysm, cost of AAA repair, Endovascular Repair, Grafts, Long-term survival, secondary outcomes
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.
Interventions
PROCEDUREEndovascular Repair
Endovascular Repair
PROCEDUREStandard Open Repair
Standard Open Repair
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | Participants were followed for the duration of the study, up to 9 years | Participants vital status was assessed from randomization to end of study follow-up \[10/15/2011\] or death \[whichever occurred first\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SF-36 Mental Component Score (MCS) | Outcome was assessed at 6 months and then yearly, up to 9 years | 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. |
| SF-36 Physical Component Score (PCS) | Outcome was assessed at 6 months and yearly thereafter, up to 9 years | 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. |
| SF-36 Physical Component Deaths Included Score (PCTD) | Outcome was assessed at 6 months and yearly thereafter, up to 9 years | 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. |
| Secondary Therapeutic Procedures | Participants were followed for the duration of the study, up to 9 years | 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. |
| European Quality of Life-5 Dimension (EQ-5D) Visual Analog Scale | Outcome was assessed at 6 months and yearly thereafter, up to 9 years | 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. |
| International Index of Erectile Function (IIEF-5) | Outcome was assessed at 6 months and yearly thereafter, up to 9 years | 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. |
| European Quality of Life-5 Dimension (EQ-5D) Index Score | Outcome was assessed at 6 months and yearly thereafter, up to 9 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Endovascular Repair Endovascular Repair | 444 |
| Open Repair Standard Open Repair | 437 |
| Total | 881 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 146 | 146 |
Baseline characteristics
| Characteristic | Open Repair | Endovascular Repair | Total |
|---|---|---|---|
| Age, Continuous | 70.5 years STANDARD_DEVIATION 7.8 | 69.6 years STANDARD_DEVIATION 7.8 | 70.1 years STANDARD_DEVIATION 7.8 |
| Body Mass Index [BMI] | 28.7 Kg/m^2 STANDARD_DEVIATION 5.6 | 28.6 Kg/m^2 STANDARD_DEVIATION 5.2 | 28.6 Kg/m^2 STANDARD_DEVIATION 5.4 |
| Currently Smoking No | 244 Participants | 274 Participants | 518 Participants |
| Currently Smoking Yes | 193 Participants | 170 Participants | 363 Participants |
| Maximum Aneurysm Diameter | 5.7 Centimeter STANDARD_DEVIATION 1 | 5.7 Centimeter STANDARD_DEVIATION 0.8 | 5.7 Centimeter STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 435 Participants | 441 Participants | 876 Participants |
| Smoking Status Ever Smoked | 413 Participants | 428 Participants | 841 Participants |
| Smoking Status Never Smoked | 24 Participants | 16 Participants | 40 Participants |
| Surgical Risk [RAND Score] High | 29 Participants | 31 Participants | 60 Participants |
| Surgical Risk [RAND Score] Intermediate | 175 Participants | 169 Participants | 344 Participants |
| Surgical Risk [RAND Score] Low | 228 Participants | 240 Participants | 468 Participants |
| Surgical Risk [RAND Score] Not Assessed | 5 Participants | 4 Participants | 9 Participants |
| Weight in kilograms | 89.7 Kilogram STANDARD_DEVIATION 17.8 | 89.9 Kilogram STANDARD_DEVIATION 16.8 | 89.8 Kilogram STANDARD_DEVIATION 17.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 127 / 444 | 177 / 437 |
| serious Total, serious adverse events | 336 / 444 | 329 / 437 |
Outcome results
Primary
All-cause Mortality
Participants vital status was assessed from randomization to end of study follow-up \[10/15/2011\] or death \[whichever occurred first\].
Time frame: Participants were followed for the duration of the study, up to 9 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Endovascular Repair | All-cause Mortality | 146 participants |
| Open Repair | All-cause Mortality | 146 participants |
Comparison: The primary outcome was long-term, all-cause mortality. The sample size would provide 80% power to detect a 25% relative reduction in mortality at a two-sided alpha level of 0.05. The primary comparison was the main effects of Endovascular repair vs Open repair of AAA.p-value: 0.8195% CI: [0.77, 1.22]Log Rank
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.
Time frame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Endovascular Repair | European Quality of Life-5 Dimension (EQ-5D) Index Score | -3.67 units on a scale |
| Open Repair | European Quality of Life-5 Dimension (EQ-5D) Index Score | -3.17 units on a scale |
Comparison: Note: Since this is measuring change over time since baseline, values could be below 0.p-value: 0.58Mixed Models Analysis
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.
Time frame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Endovascular Repair | European Quality of Life-5 Dimension (EQ-5D) Visual Analog Scale | -0.04 units on a scale |
| Open Repair | European Quality of Life-5 Dimension (EQ-5D) Visual Analog Scale | -0.03 units on a scale |
p-value: 0.37Mixed Models Analysis
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.
Time frame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Endovascular Repair | International Index of Erectile Function (IIEF-5) | -3.54 units on a scale |
| Open Repair | International Index of Erectile Function (IIEF-5) | -3.73 units on a scale |
p-value: 0.68Mixed Models Analysis
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.
Time frame: Participants were followed for the duration of the study, up to 9 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Endovascular Repair | Secondary Therapeutic Procedures | 98 participants |
| Open Repair | Secondary Therapeutic Procedures | 78 participants |
p-value: 0.12Chi-squared
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.
Time frame: Outcome was assessed at 6 months and then yearly, up to 9 years
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Endovascular Repair | SF-36 Mental Component Score (MCS) | -0.77 units on a scale |
| Open Repair | SF-36 Mental Component Score (MCS) | -0.66 units on a scale |
p-value: 0.81Mixed Models Analysis
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.
Time frame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Endovascular Repair | SF-36 Physical Component Deaths Included Score (PCTD) | -7.30 units on a scale |
| Open Repair | SF-36 Physical Component Deaths Included Score (PCTD) | -6.98 units on a scale |
p-value: 0.78Mixed Models Analysis
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.
Time frame: Outcome was assessed at 6 months and yearly thereafter, up to 9 years
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Endovascular Repair | SF-36 Physical Component Score (PCS) | -3.18 units on a scale |
| Open Repair | SF-36 Physical Component Score (PCS) | -3.05 units on a scale |
p-value: 0.8Mixed Models Analysis