Macroplastique® Clinical Data
Macroplastique has been used in Europe since 1991 with excellent clinical results. View the bibliography for a list of articles on the use of Macroplastique for Adult Female Stress Urinary Incontinence.
A Macroplastique publication highlights the 12-month results from the FDA premarket approval study which reinforced the exceptional performance of Macroplastique as compared to the control, an absorbable bulking agent.
Click the article title to view the full abstract from this publication.
Cross-linked polydimethylsiloxane injection for female stress urinary incontinence: Results of a multicenter, randomized, controlled, single-blind study. By Ghoniem, G. et al. (2009). J Urol. 181, 204-210.
Excerpt from the Macroplastique Instructions for Use
The following is an excerpt from the Macroplastique Instructions for Use which also reviews the results of this clinical study.
The Macroplastique clinical study was a prospective, multicenter, single-blind, randomized controlled trial. This study was designed to evaluate Macroplastique in a pivotal trial and was conducted to determine the safety and effectiveness of Macroplastique implants as a minimally invasive, transurethral endoscopic treatment of female stress urinary incontinence (SUI) primarily due to intrinsic sphincter deficiency (ISD).
To be eligible for enrollment, subjects were required to be adult women diagnosed with SUI primarily due to ISD, and to have viable mucosal lining and normal bladder capacity. Subjects with urinary tract infections, uncontrolled bladder instability, high post void residual urine volume, prolapse greater than stage II, confounding bladder pathology, as well as subjects who were pregnant or morbidly obese were excluded.
Two hundred sixty subjects were enrolled in the study, of which, two hundred forty-eight patients were randomized 1:1 and treated with either Macroplastique or a Control device (a commercially available absorbable urethral bulking agent). Two hundred forty-seven subjects were treated in accordance with their randomization.
Only one subsequent treatment was allowed. If performed, the second treatment took place within one month after patients' 3-month follow-up in both study arms. Evaluation of study endpoints was performed 12 months after the patient's last treatment.
Primary Effectiveness Endpoint
Continence status was determined by evaluating patients prior to treatment through twelve months follow-up using the Stamey incontinence grading described as follows:
- Grade 0: Continent or dry
- Grade 1: Patient loses urine with sudden increases in abdominal pressure, but never in bed at night
- Grade 2: Patient's incontinence worsens with lesser degrees of stress, such as walking, standing erect from a sitting position, or sitting up in bed
Grade 3: Patient has total incontinence and urine is lost without any relation to physical activity or position
The primary endpoint in the study was the percentage of patients demonstrating improvement of at least one Stamey Grade from baseline to 12 months after last treatment. The primary endpoint was analyzed using a non-inferiority hypothesis with a 15% delta for Macroplastique versus Control. Pad weight, dryness, and quality of life (I-QoL) were assessed as secondary endpoints at 12 months.
All adverse events associated with the clinical study were summarized and classified according to severity, duration, and relationship to the device and/or the treatment. In order to minimize potential bias, all genitourinary adverse events were conservatively classified as treatment related.
All study objectives were met in the Macroplastique trial. Tables 1 through 4 present data from the multicenter clinical trial for the Intent-to-Treat and Per Protocol patient populations. The Intent-to-Treat population includes all 260 subjects enrolled in the study (130 Macroplastique and 130 Control); the Per Protocol population excludes those subjects who were neither implanted nor followed and also excludes 1 subject treated contrary to her randomization for 122 Macroplastique and 125 Control subjects. Patients whose outcomes were unknown at 12 months are automatically analyzed as failures using both the Intent-to-Treat and Per Protocol analysis methods.
Table 1: Patient Baseline Information
|Patient Baseline Information||Macroplastique||Control|
|Mean age (range)||60.5 years (27-85)||61.6 years (34-90)|
|Mean duration of incontinence||11.3 years||11.0 years|
|Patients with baseline Stamey grade = 1||30%||39%|
|Patients with baseline Stamey grade = 2||68%||54%|
|Patients with baseline Stamey grade = 3||2%||7%|
|Baseline pad weight||28 grams||28 grams|
|Baseline I-QoL score||49.3||48.2|
Table 2: Treatment Information
|Mean number of treatments per patient during study||1.5||1.6|
|Patients receiving a single treatment||47.5%||41.3%|
|Patients receiving two treatments||52.55||58.7%|
|Mean initial volume injected per patient||4.6ml||4.6ml|
|Mean re-treatment volume injected per patient||4.3ml||4.5ml|
|Mean total volume injected per patient||6.8ml||7.2ml|
Analysis of the primary endpoint demonstrated that Macroplastique was statistically non-inferior to the Control bulking agent for the endpoint of improvement in Stamey Grade at 12 months, where "non-inferior" is defined statistically as the study arm is not worse than the control arm (with a tolerable margin of 15%).
Table 3: Key Effectiveness Results at 12 Months (Intent-to-Treat)
|Dry||34.6% (45/130)||23.8% (31/130)|
|Improvement of ≥ 1 grade||57.7% (75/130)||46.9% (61/130)|
|Same||19.2% (25/130)||24.6% (32/130)|
|Worse / Unable to assess||23.1% (30/130)||28.5% (37/130)|
|≥ 50% improvement||60.0% (78/130)||53.1% (69/130|
|0-49% improvement||6.9% (9/130)||7.7% (10/130)|
|Worse / Unable to assess*||33.1% (43/130)||39.2% (51/130)|
*No 12-month data was available for the Unable to assess group; these subjects were analyzed as failures.
Table 4: Key Effectiveness Results at 12 Months (Per Protocol)
|Dry||36.9% (45/122)||24.8% (31/125)|
|Improvement of ≥ 1 grade||61.5% (75/122)||48.8% (60/125)|
|Same||20.5% (25/122)||25.6% (32/125)|
|Worse / Unable to assess||18.0% (22/122)||26.4% (33/125)|
|≥ 50% improvement||63.9% (78/122)||54.4% (68/125|
|0-49% improvement||7.4% (9/122)||8.0% (10/125)|
|Worse / Unable to assess*||28.7% (35/122)||37.6% (47/125)|
|Quality of life (as followed)|
|Mean improvement in I-QoL||28.7||26.7|
*No 12-month data was available for the Unable to assess group; these subjects were analyzed as failures.
Twenty-four month follow-up Stamey Grade data were available on 84 Macroplastique subjects. Of these 84 subjects, 63 had improvement in Stamey Grade at 24 months, 28 of whom were dry.
The Macroplastique clinical trial involved 186 Macroplastique treatments in 122 subjects. A total of 303 treatment related adverse events (including transient symptoms) in 96 patients were reported in the Macroplastique arm. In order to reduce potential bias, all genitourinary adverse events were analyzed as treatment related regardless of time period reported (i.e., a urinary tract infection occurring at either 1 month or 12 months post treatment was considered a treatment related adverse event). The severity of treatment related adverse events was noted as "serious" or "not serious"; there were no serious treatment related adverse events reported in the Macroplastique arm. There was one death of a Macroplastique patient due to respiratory failure secondary to cancer, which was determined to be not related to the treatment.
In the randomized trial comparing Macroplastique to a control urethral bulking agent, the proportion of patients experiencing treatment related and/or genitourinary adverse events were similar across treatment groups with no significant differences found either overall or for any specific event. The incidence for the most prevalent treatment related adverse events reported in the multicenter evaluation is listed in Table 5.
Table 5: Number (%) of Subjects Reporting Treatment Related Adverse Events
|Event Category||(n = 122)|
|Post-procedure catheterization (see paragraph below)||53 (43.4%)|
|Urinary tract infection (UTI) (including bladder infection)||31 (25.4%)|
|Urinary retention||26 (21.3%)|
|Hematuria (including transient hematuria)||19 (15.6%)|
|Pain at implantation site||16 (13.1%)|
|Slowed urine stream||9 (7.4%)|
|Incomplete bladder emptying||7 (5.7%)|
|Urge incontinence||7 (5.7%)|
|Vaginal bleeding||4 (3.3%)|
|Yeast infection||4 (3.3%)|
|Bladder pain||3 (2.5%)|
|Increased/worsening nocturia||3 (2.5%)|
|Overactive bladder (OAB)||3 (2.5%)|
|Number of Other Events1||29 (N/A)|
1 "Other" treatment related adverse events in Macroplastique subjects, occurring at frequencies of < 2%, were as follows (listed alphabetically): abdominal pain, allergic reaction - control bulking agent skin test, bolus ruptured, change in urine stream, diarrhea, dizziness, filling defect, headache, increased AM urge incontinence, joint pain during urination, nausea, partial urethral closure, pelvic tenderness, perineal discomfort/pain, sleep disturbance, spotting between periods, tiredness, urethral erosion, uterine polyp, vaginal discharge, vaginal itching, visible product, and vulvar lesion.
Placement of an in/out catheter immediately post-procedure is commonly performed and was included in the clinical trial protocol as a way to drain the bladder at the end of the procedure. The duration of placement was brief and did not disrupt the newly placed bulking agent bolus. Five subjects (4 Macroplastique, 1 Control) were sent home with an indwelling catheter, which was removed the next day. An additional Macroplastique subject had a Foley catheter placed for 48 hours to address her retention. While the proportion of Macroplastique patients with in/out catheters was statistically higher when compared with Control, this event is not clinically significant, particularly since the protocol allowed for this practice.
Two cases of urethral erosion were observed in the Macroplastique arm. Neither case was reported due to patient complaint, but rather was observed during regular patient follow-up visit by study-related cystoscopy. One of the cases resolved spontaneously while the other case's resolution status was not specifically evaluated on follow-up cystoscopy and is listed as unknown. The patient in each case received subsequent reimplantation with Macroplastique.
Excluding transient symptoms reported during treatment, a total of 154 treatment related/genitourinary adverse events reported for Macroplastique subjects were analyzed for time-to-onset and resolution. This information was not typically reported for transient symptoms. Of these 154 events, 89 (57.8%) occurred within 30 days of the most recent treatment date, 35 (22.7%) occurred more than 30 days from the most recent treatment date and 30 (19.5%) had an unknown onset date. The resolution status at the time of database closure of the 154 treatment related events was as follows: 124 resolved (80.5%), 15 were reported as ongoing (9.7%) and 15 had unknown resolution status (9.7%). ; Of those reported as resolved, 73 resolved within 30 days of onset, 30 resolved after more than 30 days from onset and 21 had unknown onset dates/resolution dates. The 30 events reported as ongoing or unresolved at closure are: abdominal pain (1), bladder infection (1), bladder infection symptoms (1), change in urine stream (2), dysuria (2), filling defect (1), frequency (1), hesitancy (2), incomplete bladder emptying (2), overactive bladder (1), pelvic tenderness (1), spotting between periods (1), sleep disturbance (1), slowed urine stream (2), tenderness at implant site (1), transient hematuria (2), urethral erosion (1), urgency (3), urge incontinence (3), vaginal discharge (1).