Adverse Events - Merit Medical Embosphere Mode D'emploi

Quality of Life
The SF-12 Health Status questionnaire was used to assess changes in
general physical and mental health status following treatment. The goal
of this endpoint was to demonstrate at least a moderate improvement in
the overall quality of life. Results of the SF-12 Health Status questionnaire
are presented in Table 4. This 12-question questionnaire is scored and
normalized to a mean score of 50 and a standard deviation of 10 for the
general U.S. population. The mean physical and mental summary score
for patients before embolization was 45. The physical summary score
increased to 51.8 by 3 months and to 53.7 by 36 months, whereas the
mean mental score was 52.1 at 3 months and 53.3 at 36 months. The
patient's perception of health status correspondingly increased, from a
mean of 69.5 to 86.3 by 36 months. At the conclusion of the study, 84%
of patients were very or moderately satisfied with the symptom control
of the procedure.
Table 4 – Results of SF-12 Questionnaire with Regard to Overall
Health Status and Satisfaction with Outcome
Physical status
Mean
score P
Range
standard value
deviation
Before
Treatment
45±8.3 26–61.6
(n =96)
3 mo
51.8±6.7 22.3–58.5 <.001 52.1±7.7 23.8–61.6 <.001 82.6±14.2
(n =88)
6 mo
52.4±6.2 23.3–62.6 <.001 52.9 ±7.9 20.5–60.8 <.001 85.1±11.3
(n =88)
12 mo
53.6±5.9 23.1–64.1 <.001 52.6±7.8 23.2–61.7 <.001 86.4±14.2 0–100
(n =82)
24 mo
52.5±6.3 24.8–59.8 <.001 53.8±7.7 21.8–64.3 <.001 83.9±15.3 0–100
(n =73)
36 mo
53.7±5.1 30.7–62.8 <.001 53.3±7.4 25.2–63.1 <.001 86.3±11.2 48–100 52 (85%)
(n=61)
Secondary Efficacy Endpoints
Fibroid and Uterine Volume
Uterine imaging by MRI or ultrasound for UFE patients did not extend past
the 6-month follow-up. Uterine and fibroid volumes were calculated using
the formula for the volume of a prolate ellipse (LxWxDx0.52). Significant
decreases in both uterine volume (measured as including the cervix) and
uterine fibroid volume were recorded for the UFE group by the 3-month
evaluation, with further improvements seen at 6 months (p<0.001 at both
time periods as compared to baseline). Table 5 summarizes the percent
changes in uterine and fibroid volumes at 6 months following treatment.
This table includes uterine volume data from 91 of the 108 UFE Phase II
patients (84%) and fibroid volume data from 83 of these patients (77%)
who had complete and evaluable imaging reports at baseline, and at
3 months and 6 months following UFE treatment. Increases in uterine
volumes were reported for 11 patients (12%) and increases in fibroid
volumes for 8 patients (8%) by the 6-month evaluation.
Table 5 – Percent Change in Uterine and Fibroid Volumes from
Baseline
Uterine Volume (cc)
N
Mean
Range
Fibroid Volume (cc)
N
Mean
Range
A positive percent change indicates a decrease in volume, while a negative percent change indicates an
increase in volume.
Patient Satisfaction
Ninety-two of 100 UFE patients (92%) who completed the patient
satisfaction questionnaire at 6 months were slightly, moderately or very
satisfied with the outcome of their procedure, with the majority being
very satisfied. Satisfaction remained relatively high three years after UFE
Parameter Evaluated
Overall health status No. of
Mental status
Mean Mean
score P score
Range Range
standard value standard
deviation deviation
45±11.5 22.3–63.4 69.5±19.1 0–100
28.7–
100
43.8–
100
% Decrease at 6 Months
91
33.2% (30.5%)
-93.6% to 82.0%
83
50.9% (41.7%)
-173.4% to 99.7%
treatment, with 52 out of 61 patients (85%) surveyed reported they were
moderately or very satisfied.

ADVERSE EVENTS

Adverse event data is reported for all 132 patients for up to 6 months
after being treated by UFE (Table 6). There were no unanticipated adverse
device effects or unanticipated adverse events reported in this study. Table
6 presents 51 adverse events judged to be probably or possibly associated
with the procedure, which occurred in 37 of the 132 UFE patients (28%).
Seven of the 51 events (14%) occurred during the UFE procedure, five
(10%) between the procedure and hospital discharge, 17 (33%) from
hospital discharge to 1 month post-procedure, 11 (22%) from 1 to 3
months post-procedure, 4 (8%) from 3 to 6 months post-procedure, and 7
(14%) greater than 6 months post-procedure. The most common adverse
event was an allergic reaction or rash, which occurred in 8 of the 132
patients (6%), and which were generally judged by the treating physician
to be related to the drugs or contrast agent used during the procedure.
All reactions resolved spontaneously or with treatment. Four patients
had hysterectomies following UFE, for an overall hysterectomy rate of 3%.
One hysterectomy was performed at 2 months post-UFE due to sustained
fever/possible infection. The other three were elective hysterectomies
patients
due to dissatisfaction with UFE outcome, which occurred at 2, 10, and 11
who were
months post-UFE. One patient (<1%) had a repeat UFE after her uterine
moderately
arteries were found to be patent.
or very
satisfied
Table 6 – Timing and Type of Probably or Possibly UFE-Related
Adverse Events
Event
# of Patient
Description
Complaints
78 (89%)
Hysterectomy
following
78 (89%)
UFE
Allergic
84 (91%)
reaction/
Rash
64 (88%)
Fibroid/Tissue
passage or
removal
Pain related
adverse
events
Catheter/
puncture
site related
injury
Urinary Tract
Infection/
Cystitis
Vaginal
Infection/
Vaginatis
Vaginal
Irritation/
Burning/
Discharge
Other
Total
*A total of 34 out of 132 patients (26%) experienced one or more adverse event in this study. The number of
patients in this column reflects the fact that some patients experienced more than one adverse event.
PAE CLINICAL SUMMARY
A Composite database from clinical trials and published literature
containing information from a total of 286 patients who underwent
prostatic artery embolization (PAE) using Embosphere Microspheres
for treatment of symptomatic benign prostatic hyperplasia (BPH) was
analyzed to evaluate clinical outcomes. All patients were suffering from
lower urinary tract symptoms (LUTS) due to BPH, with International
Prostate Symptom Scores (IPSS) of moderate to severe. Prostate or bladder
cancer, active urinary tract infections or prostatitis, bladder stones, and
atonia or other neurogenic conditions impacting bladder function,
and intolerance to contrast media or catheter-based interventions
were exclusionary. Prior to embolization, patients underwent clinical
evaluation, imaging of the prostate, and completed validated symptom
and quality of life questionnaires. Follow-up evaluations included the
IPSS and its quality of life (QOL) questionnaire and prostate imaging at
a minimum. The primary effectiveness evaluations were change in IPSS
6
# of In < 1
Events Procedure Hospital Month
4 4
8 8 2 3
5 6
4 4
6 7 1 2
3 4
5 7
2 2
9 9 4
46 51 7 5
1-3 3-6 > 6
Months Months Months
2 2
3
2 3 1
3 1
4
1 1 1 1
2 1 2 2
1 1
1 2 1 1
17 11 4 7