Ulipristal Use in Chinese Population

Study Overview
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Brief Summary
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Uterine leiomyomas is the commonest benign tumour of the female genital tract. It lead to menorrhagia, anaemia, pain and pressure symptoms. Due to the enlarged uterus, the use of minimal invasive surgery is limited. There is also increase risk of intraoperative blood transfusion. Ulipristal acetate (UPA) is a selective progesterone-receptor modulator (SPRM). Preoperative use of Ulipristal for 12 weeks has been shown to decrease uterine bleeding, fibroid volume, pre-operative anaemia and symptoms severity. However there is still lacking evidence in terms of long term safety and efficacy, especially in Chinese population. The aim of the present study is to evaluate the effect and safety on preoperative use of Ulipristal on fibroid.

Detailed Description
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Uterine leiomyomas is the commonest benign tumour of the female genital tract. It is often asymptomatic, but can also lead to anaemia, pain and pressure symptoms. It is the commonest indication for hysterectomy, especially abdominal hysterectomy. Currently, the use of hormonal treatment is associated with side effects including gastrointestinal upset, bloating, weight gain and thromboembolic risks. The main stay for treatment relies on surgery. Furthermore, the use of minimal invasive surgeries is limited by the size of the fibroids. Preoperative use of Gonadotrophic Releasing Hormone analogues (GnRHa) is effective in shrinkage of the uterine leiomyomas and reduction of uterine bleeding. However, postmenopausal symptoms including hot flushes, vaginal dryness are profound. Ulipristal acetate (UPA), previously named CDB-2914, is a selective progesterone-receptor modulator (SPRM). It binds to the progesterone receptors with high affinity. It inhibits follicular development and ovulation, while it has no significant effects on estradiol levels and antiglucocorticoid activity. Preoperative use of Ulipristal for symptomatic uterine fibroids has been investigated in randomized controlled study with improvement in terms of uterine bleeding, fibroids volume, pre-operative anaemia and symptoms severity. However there is still lacking evidence in terms of long term safety and efficacy. Also there is lack of evidence in Chinese population. The aim of the present study is to evaluate the effect and safety on preoperative use of Ulipristal on fibroid.

Official Title
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Pilot Study on the Pre-operative Use of Ulipristal on Fibroid in Chinese Population

Conditions
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Fibroid

Intervention / Treatment
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* Drug: Ulipristal acetate
* Other: Placebo pills
* Drug: Ferrous sulphate
* Drug: Tranexamic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for hysterectomy for symptomatic fibroid Be a Chinese Pre-menopausal With a Pictorial bleeding assessment chart score > 100 during menstruation at the preceding month Non-pregnant With a body-mass index between 18 to 30. Exclusion Criteria: History of uterine surgery (apart from Caesarean section or cervical conization), endometrial ablation or uterine artery embolization History of gynaecological malignancies History of endometrial hyperplasia Known haemoglobinopathy (e.g. thalassaemia) Known severe coagulation disorder Has one or more ovarian cysts >= 4 cm in diameter diagnosed by ultrasound History of use of Selective Progesterone Receptor Modulator (SPRM) Current (within 12 months) problem with alcohol or drug abuse. Known allergy to SPRM or ferrous sulphate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ulipristal<br>Patients will be prescribed Ulipristal acetate 5mg daily for 12 weeks before operation. If the patients have anaemia with haemoglobin less than 10g/dL, ferrous sulphate 300mg three times a day will be prescribed as well. Tranexamic Acid 500mg four times a day will be prescribed on request basis. | Drug: Ulipristal acetate<br>* Ulipristal acetate 5mg daily will be prescribed<br>* Other names: Esyma;Drug: Ferrous sulphate<br>* Ferrous sulphate 300mg three times a day will be prescribed if haemoglobin level is less than 10g/dL.<br>* Other names: Ferasul;Drug: Tranexamic Acid<br>* Tranexamic Acid 500mg four times a day on request basis will be prescribed if patient complained of menorrhagia.<br>* Other names: Transamin;|
| Placebo Comparator: Placebo<br>Patients will be prescribed placebo pills daily for 12 weeks before operation. If the patients have anaemia with haemoglobin less than 10g/dL, ferrous sulphate 300mg three times a day will be prescribed as well. Tranexamic Acid 500mg four times a day will be prescribed on request basis. | Other: Placebo pills<br>* Placebo pills will be prescribed<br>Drug: Ferrous sulphate<br>* Ferrous sulphate 300mg three times a day will be prescribed if haemoglobin level is less than 10g/dL.<br>* Other names: Ferasul;Drug: Tranexamic Acid<br>* Tranexamic Acid 500mg four times a day on request basis will be prescribed if patient complained of menorrhagia.<br>* Other names: Transamin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of uterine bleeding | Pictorial bleeding assessment chart will be used for assessment of uterine bleeding. Patients will be assessed before the start of treatment, after completion of 6 weeks course and after completion of 12 weeks course. The change of uterine bleeding after completion of 12 weeks course of treatment will be recorded. | Through study completion, an average of 14weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of haemoglobin level | The change of haemoglobin level after completion of 12 weeks course will be recorded. | Through study completion, an average of 14weeks | 
| Change of fibroid volume | The fibroid volume will be measured using ultrasonography before start of treatment, after 6 weeks course of treatment and after completion of 12 weeks course of treatment. | Through study completion, an average of 14weeks | 
| Intraoperative blood loss | The amount of blood loss at hysterectomy will be recorded. | After completion of 12 weeks course, the intraoperative blood loss at the time of performance of hysterectomy will be assessed. | 
| Conversion to less invasive intervention options | 2 weeks before scheduled operation, patients will be assessed by the operation team and the most suitable route of hysterectomy will be discussed again. The possibility of conversion to less invasive intervention options including from laparotomy to laparoscopy will be recorded. | After completion of 12 weeks course of treatment and before the scheduled operation | 
| Side effects | The side effects including nausea, vomiting, headache, dyspepsia will be recorded. | Through study completion, an average of 14weeks | 
| Histology of the operative specimen | Presence of malignancy or hyperplasia in the operative specimen will be recorded. | After completion of 12 weeks course of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibroid, Ulipristal, Selective progesterone receptor modulator, Chinese