Table 2.
Clinical EndPoints, Serious Adverse Events and Hospitalizations
| Suction-based Extraction (N=118) |
Control (N=120) |
Absolute Difference (95% CI)a | P-Valueb | Intra-aortic Filtration (N=133) |
Control (N=132) |
Absolute Difference (95% CI)a | P-Valueb | |
|---|---|---|---|---|---|---|---|---|
| Clinical Endpoints in first 7 Days | Percent (Standard Error) | Percent (Standard Error) | ||||||
| Primary Endpointc -Imputed | 68.0 (4.5) | 66.7 (4.4) | 1.3 (−11.2, 13.8) | 0.84 | 74.4 (4.1) | 67.6 (4.5) | 6.9 (−4.2, 17.9) | 0.22 |
| no./total no. of patients (%) | no./total no. of patients (%) | |||||||
| Primary Endpointc -Observed | 68/101 (67.3) | 73/112 (65.2) | 2.1 (−10.6, 14.9) | 0.74 | 86/118 (72.9) | 78/119 (65.5) | 7.3 (−4.4, 19.1) | 0.22 |
| Death ≤ 7 daysd | 0/117 (0.0) | 1/120 (0.8) | −0.8 (−2.5, 0.8) | >0.99 | 1/133 (0.8) | 1/131 (0.8) | 0.0 (−2.1, 2.1) | >0.99 |
| Radiographic Infarcts on dwMRIe | 66/101 (65.3) | 71/111 (64.0) | 1.4 (−11.5, 14.3) | 0.83 | 83/115 (72.2) | 76/118 (64.4) | 7.8 (−4.1, 19.7) | 0.20 |
| Clinically Apparent Stroke ≤ 7 daysd,f | 6/117 (5.1) | 7/120 (5.8) | −0.7 (−6.5, 5.1) | 0.81 | 11/133 (8.3) | 8/131 (6.1) | 2.2 (−4.1, 8.4) | 0.50 |
| Severity of Clinically Apparent Stroke ≤ 7 days | ||||||||
| Severe (NIHSS >20) | 1/6 (16.7) | 3/7 (42.9) | - | - | 1/11 (9.1) | 3/8 (37.5) | - | - |
| Moderate to severe (NIHSS 16–20) | 0/6 | 0/7 | - | 0/11 | 0/8 | - | ||
| Moderate (NIHSS 5–15) | 2/6 (33.3) | 1/7 (14.3) | - | - | 5/11 (45.5) | 2/8 (25.0) | - | - |
| Mild (NIHSS 0–4) | 3/6 (50.0) | 3/7 (42.9) | - | - | 5/11 (45.5) | 3/8 (37.5) | - | - |
| Clinically Apparent Stroke ≤ 3 days | 4/6 (66.7) | 6/7 (85.7) | - | - | 8/11 (72.7) | 7/8 (87.5) | - | - |
|  Severe (NIHSS >20) | 0/4 | 3/6 (50.0) | - | - | 1/8 (12.5) | 3/7 (42.9) | - | - |
| Moderate to severe (NIHSS 16–20) | 0/4 | 0/6 | - | 0/8 | 0/7 | - | ||
| Moderate (NIHSS 5–15) | 1/4 (25.0) | 1/6 (16.7) | - | - | 5/8 (62.5) | 2/7 (28.6) | - | - |
| Mild (NIHSS 0–4) | 3/4 (75.0) | 2/6 (33.3) | - | - | 2/8 (25.0) | 2/7 (28.6) | - | - |
| Delirium | ||||||||
| Day 1 | 19/111 (17.1) | 16/110 (14.5) | 2.6 (−7.0, 12.2) | 0.60 | 27/121 (22.3) | 18/119 (15.1) | 7.2 (−2.6, 17.0) | 0.15 |
| Day 3 | 15/108 (13.9) | 13/113 (11.5) | 2.4 (−6.4, 11.2) | 0.59 | 15/117 (12.8) | 18/124 (14.5) | −1.7 (−10.4, 7.0) | 0.70 |
| Day 7 | 7/112 (6.3) | 17/111 (15.3) | −9.1 (−17.1, −1.0) | 0.03 | 10/123 (8.1) | 19/122 (15.6) | −7.4 (−15.5, 0.6) | 0.07 |
| Clinical Endpoint at 30 Daysd | ||||||||
| Compositeg | 25/117 (21.4) | 29/120 (24.2) | −2.8 (−13.5, 7.9) | 0.61 | 44/132 (33.3) | 31/131 (23.7) | 9.7 (−1.2, 20.5) | 0.08 |
| Clinically Apparent Stroke | 6/117 (5.1) | 7/120 (5.8) | −0.7 (−6.5, 5.1) | 0.81 | 11/132 (8.3) | 8/131 (6.1) | 2.2 (−4.0, 8.5) | 0.49 |
| Death | 4/117 (3.4) | 2/120 (1.7) | 1.8 (−2.3, 5.8) | 0.44 | 3/132 (2.3) | 2/131 (1.5) | 0.7 (−2.6, 4.0) | >0.99 |
| AKI (Stage 1–3, Serious & Non-Serious) | 19/117 (16.2) | 24/120 (20.0) | −3.8 (−13.6, 6.0) | 0.45 | 35/132 (26.5) | 25/131 (19.1) | 7.4 (−2.7, 17.5) | 0.15 |
| no. events (rate per 100 patient months) | no. events (rate per 100 patient months) | |||||||
| Serious Adverse Events by 90 Days | ||||||||
| Acute Kidney Injuryh | 3 (0.9) | 4 (1.2) | −0.3 (−1.8, 1.3) | 0.74 | 14 (3.8) | 4 (1.1) | 2.7 (0.4, 4.9) | 0.02 |
| Stage 1 | 1 (0.3) | 0 (0.0) | 0.3 (−0.3, 0.9) | 0.32 | 3 (0.8) | 0 (0.0) | 0.8 (−0.1, 1.7) | 0.08 |
| Stage 2 | 0 (0.0) | 2 (0.6) | −0.6 (−1.4, 0.2) | 0.16 | 4 (1.1) | 2 (0.5) | 0.5 (−0.8, 1.8) | 0.42 |
| Stage 3 | 2 (0.6) | 2 (0.6) | 0 (−1.2, 1.2) | 0.97 | 7 (1.9) | 2 (0.5) | 1.3 (−0.2, 2.9) | 0.10 |
| Bleeding | 8 (2.5) | 6 (1.8) | 0.7 (−1.5, 2.9) | 0.55 | 5 (1.3) | 6 (1.6) | −0.3 (−2.0, 1.5) | 0.75 |
| Cardiac Arrhythmias | 31 (9.5) | 25 (7.4) | 2.1 (−2.3, 6.6) | 0.35 | 57 (15.3) | 30 (8.1) | 7.2 (2.3, 12.1) | 0.004 |
| Cardiac arrest | 0 (0.0) | 1 (0.3) | −0.3 (−0.9, 0.3) | 0.32 | 6 (1.6) | 2 (0.5) | 1.1 (−0.4, 2.6) | 0.16 |
| Sustained ventricular arrhythmia with defibrillation or cardioversion | 0 (0.0) | 0 (0.0) | - | - | 1 (0.3) | 0 (0.0) | 0.3 (−0.3, 0.8) | 0.32 |
| Sustained supraventricular arrhythmia with drug treatment or cardioversion | 25 (7.7) | 22 (6.5) | 1.2 (−2.9, 5.2) | 0.58 | 43 (11.6) | 25 (6.8) | 4.8 (0.4, 9.1) | 0.03 |
| Conduction abnormalities or sustained bradycardia with permanent pacemaker placement | 6 (1.8) | 2 (0.6) | 1.3 (−0.4, 2.9) | 0.15 | 7 (1.9) | 3 (0.8) | 1.1 (−0.6, 2.7) | 0.21 |
| Major Infectioni | 10 (3.1) | 12 (3.6) | −0.5 (−3.3, 2.3) | 0.73 | 15 (4.0) | 15 (4.1) | 0 (−2.9, 2.9) | 0.98 |
| Myocardial Infarction | 0 (0.0) | 0 (0.0) | − | − | 3 (0.8) | 0 (0.0) | 0.8 (−0.1, 1.7) | 0.08 |
| Neurological Dysfunction | 4 (1.2) | 10 (3.0) | −1.7 (−3.9, 0.5) | 0.12 | 7 (1.9) | 12 (3.3) | −1.4 (−3.7, 0.9) | 0.24 |
| Transient Ischemic Attack | 0 (0.0) | 1 (0.3) | −0.3 (−0.9, 0.3) | 0.32 | 0 (0.0) | 1 (0.3) | −0.3 (−0.8, 0.3) | 0.32 |
| Ischemic Strokej | 3 (0.9) | 3 (0.9) | 0 (−1.4, 1.5) | 0.97 | 4 (1.1) | 4 (1.1) | 0 (−1.5, 1.5) | 0.99 |
| Toxic Metabolic Encephalopathy | 1 (0.3) | 1 (0.3) | 0 (−0.8, 0.8) | 0.98 | 2 (0.5) | 1 (0.3) | 0.3 (−0.6, 1.2) | 0.57 |
| Seizure | 0 (0.0) | 2 (0.6) | −0.6 (−1.4, 0.2) | 0.16 | 0 (0.0) | 3 (0.8) | −0.8 (−1.7, 0.1) | 0.08 |
| Other | 0 (0.0) | 3 (0.9) | −0.9 (−1.9, 0.1) | 0.08 | 1 (0.3) | 3 (0.8) | −0.5 (−1.6, 0.5) | 0.31 |
| Renal Failure | 0 (0.0) | 2 (0.6) | −0.6 (−1.4, 0.2) | 0.16 | 1 (0.3) | 2 (0.5) | −0.3 (−1.2, 0.6) | 0.56 |
| Respiratory Failure | 3 (0.9) | 9 (2.7) | −1.8 (−3.8, 0.3) | 0.09 | 8 (2.2) | 11 (3.0) | −0.8 (−3.1, 1.5) | 0.48 |
| Heart Failure | 4 (1.2) | 8 (2.4) | −1.1 (−3.2, 0.9) | 0.27 | 2 (0.5) | 9 (2.4) | −1.9 (−3.7, −0.1) | 0.03 |
| Venous Thromboembolism Eventk | 1 (0.3) | 2 (0.6) | −0.3 (−1.3, 0.7) | 0.58 | 4 (1.1) | 2 (0.5) | 0.5 (−0.8, 1.8) | 0.42 |
| All Serious Adverse Events | 91 (28.0) | 112 (33.3) | −5.3 (−13.7, 3.2) | 0.22 | 157 (42.2) | 126 (34.2) | 8.0 (−0.8, 16.9) | 0.08 |
| Hospitalization | ||||||||
| Readmissions | 24 (8.4) | 20 (6.8) | 1.7 (−2.8, 6.1) | 0.47 | 30 (9.3) | 23 (7.1) | 2.2 (−2.3, 6.6) | 0.34 |
| Quality of Life at 90 Days | ||||||||
| Mean (sd) | Mean (sd) | |||||||
| SF12 Composite Mental Health Scorel | 55.4 (8.2) | 55.1 (8.1 | 0.4 (−1.8, 2.6) | 0.74 | 55.2 (10.2 | 54.8 (8.0) | 0.3 (−2.0, 2.7) | 0.77 |
| SF12 Composite Physical Health Scorel | 44.9 (8.3) | 44.7 (8.4 | 0.1 (−2.2, 2.4) | 0.92 | 43.0 (10.8 | 44.2 (9.0) | −1.2 (−3.7, 1.3) | 0.36 |
| no./total no. of patients (%) | no./total no. of patients (%) | |||||||
| Geriatric Depression Scale > 10m | 5/104 (4.8) | 7/108 (6.5) | −1.7 (−7.9, 4.5) | 0.60 | 13/122 (10.7) | 9/119 (7.6) | 3.1 (−4.2, 10.3) | 0.40 |
| Functional Status at 90 Days | ||||||||
| Decline in Overall Neurocognitionn | 24/81 (29.6) | 27/86 (31.4) | OR 1.1 (0.5, 2.2) | 0.82 | 28/98 (28.6) | 31/96 (32.3) | OR 0.8 (0.4, 1.5) | 0.54 |
| Modified Rankin Scale >2o | 7/110 (6.4) | 4/112 (3.6) | 2.8 (−2.9, 8.5) | 0.34 | 5/127 (3.9) | 5/123 (4.1) | −0.1 (−5.0, 4.7) | >0.99 |
| Barthel Index ≤80p | 2/105 (1.9) | 3/109 (2.8) | −0.8 (−4.9, 3.2) | >0.99 | 2/123 (1.6) | 4/120 (3.3) | −1.7 (−5.6, 2.2) | 0.44 |
| Mortality – no. | 5 | 3 | HR 1.7 (0.4, 7.2) | 0.45 | 4 | 3 | HR 1.3 (0.3, 5.9) | 0.71 |
Instead of absolute difference, the odds ratio is given for decline in overall neurocognition as the analysis is based on a logistic model adjusting for baseline score and the hazard ratio is given for mortality as the analysis was to time to event;
P values were calculated by means of the chi-square test or Fisher’s exact test for the clinical end points and the Modified Rankin Scale, Barthel Index, and Geriatric Depression Scale endpoints, Poisson regression for serious adverse events and hospitalizations, t-tests for SF-12 scores, a logistic regression model of decline adjusted for baseline score for neurocognitive decline, and the log rank test for mortality;
The primary endpoint consists of radiographic infarcts on 7-day dwMRI and/or clinically apparent stroke ≤ 7 days post-surgery. Deaths are counted as treatment failures. The denominator for the observed is the number of patients with a non-missing MRI image and/or evidence of a clinical stroke or death before 7 days.
2 patients withdrew from the trial prior to 7 days and are not included in the denominators; 1 additional patient withdrew prior to 30 days;
334 dwMRIs were evaluated by the core lab. 210 (63%) were collected using a 1.5 T scanner and 124 (37%) were 3 T.;
Five patients had evidence of a clinical infarction and either did not undergo dwMRI or had no lesions on their dwMRI, (2 in Intra-aortic Filtration, 1 in the shared control, 2 in Suction-based Extraction)
The composite clinical endpoint consists of clinically apparent stroke, acute kidney injury (AKI), or death within 30 days of surgery;
The composite clinical endpoint includes clinically apparent strokes, as well as death and AKI, that are expressed in events per patient. By comparison, the AKI AE within 90 days reflects the number of events per unit time. The composite clinical endpoint includes both serious and non-serious AKI adverse events whereas the AKI rate at 90 days are only the reported serious AKI AEs per the protocol. See supplemental appendix for AKI stage definitions.
Major infection is defined as a new clinical infection accompanied by pain, fever, drainage and/or leukocytosis that is treated by anti-microbial agents (non-prophylactic). A positive culture from the infected site or organ should be present unless strong clinical evidence indicates the need for treatment despite negative cultures.;
The composite clinical endpoint includes clinically apparent strokes, as well as death and AKI, that are expressed in events per patient. By comparison, the ischemic stroke AE within 90 days reflects the number of events per unit time. The composite clinical endpoint includes both serious and non-serious stroke adverse events and stroke events that were identified based on focal findings on serial NIHSS assessments. Whereas the ischemic stroke rate at 90 days are only the reported serious stroke AEs per the protocol.;
Venous Thromboembolism consists of Deep Vein Thrombosis, Pulmonary Embolism and Other;
SF-12 is given as mean (sd). The SF-12 composite scores are normed as T-scores (mean=50, SD=10); a higher score indicates a better health state
A Geriatric Depression Scale score of 10 or below indicates absence of depression, while a score of 11 or higher is indicative of depression;
Decline is defined as number of patients whose Z-score at day 90 decreased by 0.5 standard deviations relative to their baseline score. Z-Scores were computed relative to the study population at baseline adjusting for age, education and gender.;
A modified Rankin Scale score > 2 corresponds to ≥moderate disability (3–5) or death (6);
A Barthel Index score ≤80 corresponds to ≥mild to moderate disability