Presentations from the 34th Clinical Meeting of the AAGL Advancing Minimally Invasive Gynecology Worldwide held November 2005 in Chicago, IL, USA
The Novasys Medical RenessaT System
Vincent Lucente, MD, MBA
Medical Director, Institute for Female Pelvic Medicine and Reconstructive
Surgery
http://www.fpminstitute.com/
Welcome to this online educational program regarding the Novasys Medical RenessaT System. I am Dr. Vincent Lucente, Medical Director for the Institute for Female Pelvic Medicine and Reconstructive Surgery in Allentown, Pennsylvania. I am also a Clinical Professor at Temple University in the Department of Obstetrics and Gynecology.
During this program, we will review the technology and the overview of the RenessaT system. We will also be reviewing the clinical trials and the recent publications and presentations regarding this treatment modality.
Stress incontinence occurs when bladder outlet hypermobility is often accompanied by inappropriate opening or funneling of the bladder neck and proximal urethra. The cure for stress urinary incontinence does not require necessarily the correction of proximal urethral hypermobility, but more it requires the prevention of bladder neck and proximal urethral opening or funneling.
The Novasys Medical RenessaT System has been recently FDA approved for the treatment of female stress urinary incontinence due to hypermobility. It is a non-surgical trans-urethral treatment and involves a single in-office treatment performed under local anesthesia with oral or conscious sedation. No cystoscopy is required. The procedure has demonstrated an excellent safety profile with the patients tolerating the procedure well. There are no incisions, bandages or dressings for the patient to deal with. The recovery is rapid with minimal limitations.
The system involves a trans-urethral probe with a balloon and four needle electrodes. Each of the needles over a 60-second cycle deliver radio-frequency energy and heat forms in four submucosal sites to a temperature of 65 degrees Celsius. The rate of frequency delivery occurs over nine sites denaturing the collagen, for a total of 36 microscopic submucosal sites within the bladder neck and proximal urethra. The automatic safety features allow continuous monitoring of tissue temperatures and tissue impedance.
The mechanism of action for the RenessaT treatment involves radio-frequency delivery, causing thermal collagen denaturization. The elongated collagen chains become uncoiled and then through a tissue remodeling process or healing phase, there is a reduction in the compliance of the micro-remodeled tissue sites. The micro-remodeling is performed circumferentially within both the bladder neck and proximal urethral submucosa. This again will reduce the regional, i.e. bladder neck and proximal urethral dynamic compliance. This results in a reduction or inhibition of the inappropriate bladder neck or proximal urethral opening or funneling associated with bladder descent during rises in inter-abdominal pressure during stress activity. The final result is either a reduction or a prevention in the symptom of stress urinary incontinence.
This slide demonstrates the histological changes seen in the animal models. There is a subnecrotic submucosal target resulting in local collagen denaturization. There is no effect on the overlying mucosa or the deeper urethral wall tissues. The healed submucosal site measures only 200 microns in diameter. Most importantly, there is no luminal narrowing or stricture of the urethra.
As a functional result, the reduction in bladder neck and proximal urethral dynamic compliance limits the inappropriate bladder neck and proximal urethral funneling during bladder descent associated with abrupt rises in inter-abdominal pressure during stress activity. This improves the continence mechanism without effecting normal outflow or urination.
When considering how RenessaT fits into our armamentarium for the management of stress urinary incontinence, it really needs to be placed within the spectrum of interventions, from the least invasive pelvic floor muscle exercises, or Kegels, to perhaps the most invasive open surgical slings and bladder neck suspensions. Within that continuum, decisions will be reached between you as a physician and the patient in terms of the effectiveness and therapeutic index of each modality. The RenessaT system falls into the area of the most least invasive to the most minimally invasive in that it is available in your office setting with an extremely high safety profile.
There are several pre-clinical or animal studies, totaling approximately 200 animals, over a five-year period.
The human trials involved the pilot clinical trial, a prospective open-labeled, non-controlled five-arm design with 57 women over a two-year period. The US clinical trial was a prospective randomized sham-controlled design with 110 patients treated and 63 sham-treated subjects over a one-year period. A pilot in-office anesthesia clinical trial, also a prospective open-labeled five-arm design with 16 women with only a one-month follow-up. Finally, the US clinical trial was a prospective open-label single-arm design with 33 women over a 12-month follow-up, which is on-going.
The US clinical trial, again prospective randomized sham-controlled, involved ten sites across the US. Investigators consisted of urologists, urogynecologists and gynecologists. Both academic and private practice settings were involved. A 12-month follow-up with an extension to 36 months is underway. It was for the purpose of demonstrating the safety and effectiveness of the treatment in the outpatient setting with intravenous conscious sedation.
This slide demonstrates the baseline characteristics between the treatment arm and the sham treatment arm. There are no differences in any of the categories, including the mean age in years, the mean stress urinary incontinence duration also measured in years, body mass index, pre-menopausal incidence, mean Valsalva leak point pressure and mean I-QOL score.
The 12-month treatment effectiveness outcomes are demonstrated in this slide. The objective outcome measures in terms of Valsalva leak point pressure show that the treated women experienced an elevation in the mean Valsalva leak point pressure. The sham-treated women, however, experienced a reduction in the mean Valsalva leak point pressure consistent with on-going and/or progressive disease. This difference was statistically significant. Subject of outcome measure defined as a greater than 10 point I-QOL score demonstrated that treated women with moderate to severe baseline stress urinary incontinence experienced a statistically significantly greater incidence of at least a 10 point I-QOL score improvement relative to the sham arm. All women, mild, moderate and severe, experienced a greater incidence of at least a 10 point I-QOL score.
Here we see a bar graph demonstrating the 12-month treatment effective outcomes. Fewer daily episodes, n of 75, was experienced in 76% of the patients; fewer daily pad use for an n of 60 demonstrated 68% of the patients achieved a fewer daily pad use; zero pad use was also demonstrated in 58% of the patients; reduction in leak severity, 73% of the patients; I-QOL score improvement, 67% of the patients; and, finally, complete continence cure was experienced in 35% of the patients.
In terms of safety outcomes, there were no device-related serious adverse events. The prevalence rates for a non-serious device-related adverse event were statistically no different for subjects who received treatment and subjects who received the sham treatment, which consisted of a brief bladder catherization with the RenessaT probe. In brief, the safety profile of the RenessaT treatment was not statistically different than that of the brief bladder catherization.
The office anesthesia regimen in the US trial consisted or oral antibiotics, quinolone, either Ciprofloxacin or Levofloxacin, a 10 mg oral dose of diazepam as a sedative, 10 cc of 2% lidocaine with epinephrine, with 5 cc injected bilaterally using a 1.25 inch 25-gauge needle.
The bilateral periurethral injection is easily performed based solely on visualization.
An in-office anesthesia trial demonstrated an overall feasibility with 33 out of 33 women successfully completing the treatment. Routine post-operative recovery time averaged 15 to 20 minutes. Safety was demonstrated with no serious adverse events or no device or procedure-related adverse events. In terms of patient comfort, patients demonstrated a pre-discharge mean visual analogue score of 1.4, plus or minus 1.8, and 42% of the patients selected zero or no pain on pre-discharge visual analogue score.
Numerous abstracts have been accepted and presented at national and international meetings regarding continence and pelvic floor disorders beginning with the International Incontinence Society Meeting in 2002, as well as the more recent meeting in 2005.
There have been several peer-reviewed publications in both the International Urogynecology Journal, as well as the American Journal for Obstetrics and Gynecology. Other publications are pending.
In summary, the Novasys Medical RenessaT System is a less invasive treatment option for the management of female stress urinary incontinence. RenessaT has been shown to improve symptoms with 78% of the women showing measurable improvement in stress urinary incontinence and 35% achieving total dryness. The RenessaT system has also been shown to be extremely safe with no significant adverse events. The procedure can be performed effectively in the office under local anesthesia.
In conclusion, RenessaT is a new safe and effective option for women who are seeking a minimally invasive treatment for problematic stress urinary incontinence.