Clinical trial NCT05837624: Estetrol/Drospirenone to Reduce the Average Size of Endometriomas
Official title: Estetrol/Drospirenone to Reduce the Average Size of Endometriomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Ovarian Endometrioma
Endometrioma
Keywords: Estetrol/drospirenone
Nextstellis
Endometriosis
volume reduction
ultrasound
Estetrol-drospirenone
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2023-05-01
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Endometriosis, a chronic gynecological disorder associated with pain and infertility, is a common condition affecting approximately one in ten women. Up to 50% of patients with endometriosis have ovarian endometriomas (or "chocolate cysts"). These cysts directly impact fertility and ovarian reserve (ie. ability to have children) and can cause additional symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture, or more rarely twisting). While endometriomas tend to require surgical excision as a solution, medical management with a variety of medications has been shown to be effective in reducing their size.

Medical management (ie. medications and treatments that don't involve surgery) to reduce cyst size can help relieve symptoms either as a long term solution, before fertility treatments, or temporarily until surgery can be offered. Because the COVID-19 pandemic caused significantly reduced access to surgery and resources, medical management has become important for relief of the overburdened healthcare network.

The purpose of this study is to see how effective Estetrol/drospirenone, a combined oral contraceptive (COC), is in the reduction of ovarian endometriomas after a 3- and 6-month period of treatment.

This single arm interventional study will recruit women 18 years or older with an ovarian endometrioma of at least 3cm, who are seeking a hormonal treatment for their endometrioma(s). Consenting participants of the study will take Estetrol/drospirenone once daily, orally, for a 6 month duration. An ultrasound assessment of ovarian endometrioma(s) will be performed before starting the drug (0 months), and will be repeated at 3-months and 6-months time. At each of these hospital visits (0, 3 \& 6 months), participants will have their weight and blood pressure measured, and they will complete questionnaires regarding their endometriosis symptoms, incidence of amenorrhea, compliance and incidence of any adverse effects.

Detailed description: Ovarian endometriomas (or "chocolate cysts") are present in up to 50% of patients with endometriosis - a chronic gynecological disorder associated with pain and infertility. These cysts directly impact fertility and ovarian reserve and can cause additional symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture, or more rarely torsion).

While endometriomas tend to require surgical excision for definitive resolution, medical management with a variety of agents has been shown to be effective in reducing their size; these agents include combined oral contraceptives (COC), aromatase inhibitors, progestins, androgens, cabergoline, and gonadotropin-releasing hormone agonists (GnRH-a). Medical management to reduce their size can help alleviate symptoms indefinitely without damaging ovarian reserve prior to fertility treatments, or to temporize until surgical management can be offered. Medical management has become particularly important in light of the COVID-19 pandemic, with significantly reduced access to surgery, and resource allocation to alleviate an overburdened healthcare network.

Estetrol/drospirenone (Nextstellis™) is a prescription-only COC available in Canada containing two hormones: a progestin (drospirenone - well known as both a standalone contraceptive and in other combined formulations), and an estrogen (estetrol - newly introduced with this product). While ethinyl estradiol (EE) is the most common estrogen currently used in COC, estetrol (E4) has proven safety and tolerability, and emerging evidence points towards a lower risk of thrombosis than traditional EE used in other COC. Studies have documented efficacy and safety for the combination estetrol/drospirenone, with a favourable bleeding profile, and very low rates of adverse reactions. While there exists already encouraging data on drospirenone and drospirenone containing products on alleviating symptoms of endometriosis and reducing the size of endometriomas, there are no studies to date evaluating this novel combination of estetrol/drospirenone in managing ovarian endometriomas.

The primary objective of this study is to determine the effectiveness of Estetrol/drospirenone, a combined oral contraceptive (COC), in the reduction of ovarian endometriomas after a 3- and 6-month period of treatment.

This is a single-center, open label, single arm interventional study that will be performed at the McGill University Health Centre (MUHC) Royal Victoria Hospital (RVH). Women 18 years of age or older with at least one ovarian endometrioma, of at least 3cm, who are seeking a hormonal treatment for their endometrioma(s), will be recruited. The study will aim to recruit 21 women.

Consenting participants will be given a 6-month course of oral estetrol/drospirenone (15 mg estetrol monohydrate / 3 mg drospirenone) once daily for the study duration. An ultrasound assessment of ovarian endometrioma(s) will be performed prior to drug initiation (baseline), and will be repeated at 3-months and 6-months time. All ultrasounds will be performed by the same ultrasonographer using a standardized technique and 3-D volumetric assessment. At each of these hospital visits, participants will have their weight and blood pressure measured and they will complete questionnaires regarding their endometriosis symptoms with a research coordinator. Safety, tolerability, and the incidence of adverse effects will also be monitored at the same time intervals.

Eligibility criteria: Inclusion Criteria:

* Equal to or greater than 18 years old
* Has at least one ovarian endometrioma, of at least 3 cm
* Seeking a hormonal treatment for their endometrioma(s)

Exclusion criteria:

* Any allergy or contraindication to the study drug
* Inability to provide informed consent
* Any hormone use, from the following list, within last 3 months (excluding hormones used for ovarian stimulation for fertility treatments): Estrogen (agonist or antagonist), Progestogen (agonist or antagonist), Androgen (agonist or antagonist), GnRH (agonist or antagonist), Cabergoline

Primary outcomes:
measure: Change in ovarian endometrioma volume at 6-months (from baseline)
timeFrame: pre-study, 6-months of treatment
Secondary outcomes:
measure: Change in endometrioma volume at 3-months (from baseline)
timeFrame: pre-study, 3-months of treatment
measure: change in endometrioma maximal diameter at 6-months (from baseline)
timeFrame: pre-study, 6-months of treatment
measure: change in endometrioma maximal diameter at 3-months (from baseline)
timeFrame: pre-study, 3-months of treatment
measure: Incidence of amenorrhea
timeFrame: pre-study, 3-months of treatment, 6-months of treatment
measure: Change in patient reported endometriosis symptoms
timeFrame: pre-study, 3-months of treatment, 6-months of treatment
measure: Change in weight
timeFrame: pre-study, 3-months of treatment, 6-months of treatment
measure: Change in blood pressure
timeFrame: pre-study, 3-months of treatment, 6-months of treatment
measure: Incidence of adverse effects (safety, tolerability)
timeFrame: 3-months of treatment, 6-months of treatment
measure: Compliance
timeFrame: 3-months of treatment, 6-months of treatment
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Andrew Zakhari, M.D.
role: PRINCIPAL_INVESTIGATOR
References: