Evaluation of a Personalizable Pessary for Pelvic Organ Prolapse

Purpose: Pelvic organ prolapse (POP) impacts 50% of Canadian women in their lifetime. POP can be associated with voiding dysfunction, bowel dysfunction, and sexual dysfunction, thereby impacting quality of life. Pessaries are insertable devices used to conservatively manage POP, avoiding surgery. While surgery is effective for managing POP is effective in the short term, recurrence is common and occurs in at least 30% of patients. Traditional pessaries have not undergone any design changes in the last 50 years, and up to 30% of patients can not find a pessary that fits them well. Of the patients who do find a well fitting pessary, not all patients are independent with pessary care and up to 50% will discontinue their use in the first year either due to this lack of independence with care or due to complications associated with their use. With the advent of 3D printing technology, the possibility for a personalizable and easier to use design has become a reality. The investigators have designed a novel personalizable pessary (NPP) to address the shortcomings of traditional vaginal pessaries.

Hypothesis: The NPP will be non-inferior to standard pessaries with regards to efficacy and safety.

Null Hypothesis: The mean difference score (μ study pessary-control) between baseline and study pessary on the Pelvic Floor Distress Inventory 20 (PFDI-20) is greater than 18.3, the upper equivalence limit, or lower than -18.3, the lower equivalence limit.

Justification: Pelvic organ prolapse (POP) is the descent of pelvic organs into the vagina. It is an overlooked, stigmatized, and growing women's health issue, affecting up to 50% of Canadian women. POP contributes to other pelvic floor disorders such as urinary and/or fecal incontinence, and sexual dysfunction. POP significantly affects mental health, contributing to diminished quality of life (QoL), social isolation, and increased risks of depression and anxiety. The prevalence and burden of POP are growing rapidly, tied to the growth of our aging population.

POP treatment encompasses surgical and non-surgical options. While surgery proves effective, POP recurrence rates are up to 70% within 5 years, requiring reoperation and increasing surgical complications to patients and imposing a substantial economic burden on healthcare. Moreover, wait times for POP surgery in Canada are increasing up to 50%, which further exacerbates the challenges faced by women in need of care. Vaginal pessaries are a non-surgical option to treat POP that can be very effective and are offered as first-line therapy by 75% of physicians. However, pessaries have several limitations. These include a trial-and-error fitting process, an inability to find the right fit for all patients, and difficulty in self-care (i.e., remove, clean, and reinsert). These issues can lead to complications and high discontinuation rates (up to 53% in one year). This underscores a significant predicament for patients grappling with the inability to secure an optimal pessary fit, compelling them to resort to surgery - an undesirable outcome despite the prevalent preference for non-surgical alternatives.

While pessaries have not undergone many changes over the last half century, recent advancements in 3D printing for medical applications offer an unprecedented level of control over structure geometry. Recently, initiatives to innovate personalized pessaries through 3D printing have begun by our team and others and are increasingly garnering attention. A recent editorial in the journal Urogynecology issued a "call to action" for "disruptive innovations" in pessaries to better serve this overlooked patient population. There is a significant unmet need for improved pessary treatment options to ensure inclusive non-surgical care for patients with POP.

To address the critical gap in POP treatment in the current paradigm, our team has developed a novel expansible personalized pessary by leveraging 3D printing, enabling the development of more complex shapes. This novel pessary design, inspired by the anatomical shape of the vagina, addresses challenges related to the fitting process, finding the optimal fit, performing self-care, and ultimately improving the QoL for women experiencing POP. The objective of this research is to evaluate the safety and efficacy of this novel pessary in treating the symptoms of POP in patients impacted by this condition. optimize the design of this novel pessary and demonstrate its feasibility in patients with POP. Success of this research could unlock the potential for an improved non-surgical treatment option for POP, the impact of which extends beyond Canada, offering a global impact on the well-being of women.

The study pessary is made of biocompatible silicone similar to commercially available pessaries. The material and production processes are identical to Cosm Medical's Gynethotics Pessaries, currently approved by Health Canada (Medical Device License 110149) and available on the market.

Objectives: To assess the safety and efficacy of the NPP compared to traditional pessaries. Additional areas of assessment include proportion of patients able to be fit with the NPP and proportion of patients able to self-manage use of the NPP.

Research Method/Procedures: This is a single site, prospective, open label, non-inferiority study of a medical device. This study focuses on optimizing the sizing and personalization of the NPP using physical assessment and provides an opportunity to optimize the design for improved outcomes through patient and provider feedback. Study participants will act as their own controls. Forty-three patients with varying pessary histories will be recruited. The study participants will use a standard pessary for one month. Participants will then use the NPP for 3 months. The primary endpoint is the change in PFDI-20 score when comparing the participant's use of a standard pessary, as well as a comparison of prevalence and severity of adverse events. Secondary outcomes include changes in patient-reported symptoms, sexual function, and quality of life, as well as visual analogue score ratings on ease of NPP insertion/removal and comfort. Application to Health Canada of the NPP is pending.

Plan for Data Analysis: Data will be analysed with the assistance of a statistician. The primary outcome, assessed by PFDI-20 scores, will be reported as means and standard deviations or medians and interquartile ranges (IQR), based on the normality of the distribution. Scores will be matched and compared between the traditional and study pessary devices. In instances where the distribution is normal, a two-tailed matched t-test will be utilized; conversely, the Wilcoxon Signed-Rank Test will be implemented for non-normal distributions. Furthermore, to evaluate adverse events between matched groups, McNemar's Test will be employed. Sensitivity analyses will be conducted as exploratory analyses to compare outcomes across intention-to-treat (ITT), per protocol, and as-treated subgroups.

As success criterion for the analysis, Wiegersma et al identified the minimal important change for the PFDI-20 in women opting for conservative management of prolapse as 13.5-18.3 points. The investigators will conduct two one-sample equivalence t-tests, each with an alpha of .05, to test the composite null hypothesis that the mean difference score (μStudyPessary-control) between baseline (current pessary) and study pessary is either greater than 18.3 or less than -18.3:

The investigators will reject the null hypothesis if the maximum p-value from both tests is less than 0.05.

All continuous variables will be described using means and standard deviations or medians and interquartile ranges as appropriate. For categorical variables, frequencies and percentages will be reported. Specific assessments include the Pelvic Floor Impact Questionnaire Short Form 7, Pelvic Organ Prolapse / Urinary Incontinence Sexual Questionnaire (International Urogynecological Association Revised), and objective assessments of ability to support prolapse, all treated as continuous variables. Pain associated with insertion and removal will be assessed using Visual Analog Scale scores. Success and ease of fitting, as well as ease of insertion and removal, will be categorized, while the frequency of self-management will be reported as a count or numeric variable.