Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04004884 |
| Other study ID # |
IIBSP-ULI-2019-05 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 23, 2019 |
| Est. completion date |
December 31, 2019 |
Study information
| Verified date |
July 2019 |
| Source |
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Uterine fibroids are are the most common gynecological tumor. Among the pharmacological
treatment options, ulipristal acetate (UPA) has proven to be effective in control of bleeding
and reduction of size of fibroids.
Due to the appearance of some cases of subacute severe hepatic insufficiency in patients
undergoing UPA treatment and the possible idiosyncratic effect of the drug, the European
Medicine Agency (EMA) recommended performing liver function tests before, during and after
each UPA treatment course as a minimization risk strategy to prevent drug induced liver
injury (DILI).
The aim of the present study is to evaluate whether changes in transaminase levels or other
DILI markers occur in patients receiving UPA in our center.
Description:
INTRODUCTION Fibroids are benign monoclonal tumors originated from genetically predisposed
uterine smooth muscular cells in a proper hormonal environment. Fibroid growth is dependent
on the ovarian steroids estrogen and progesterone. In vivo models have shown that
progesterone and the presence of its receptor are the main key points for fibroid growth,
being PR stimulation the primary action of estrogens.
Multiple treatment options are currently available, including surgery (hysterectomy or
myomectomy), uterine artery embolization, cryomyolysis, radiofrequency myolysis,
high-intensity focused ultrasound, and pharmacological treatment. Proper counseling about all
therapeutic approaches should be discussed with the patient, explaining pros and cons of
every treatment and taking into consideration several clinical factors such as number,
location and fibroid size, age and desire for future pregnancies. Final decision of the best
treatment should be taken according to the patient's desire.
Uterine fibroids still represent the most frequent indication for hysterectomy, which
associates a low but significant risk of vascular, intestinal and urinary complications.
Non-surgical treatments represent a good option for those young patients in order to avoid
surgical scars on uterine surface and the risk of hysterectomy. Due to the Es and Prog
dependent status, fibroid-related symptoms often cease once menopause status is achieved, so
selected perimenopausal patients could also benefit from those therapies and avoid a surgery.
Among the pharmacological treatment options, gonadotropin-releasing hormone agonists (GnRHa)
are effective in reducing bleeding and uterine volume, but with considerable side-effects due
to the estrogen-suppression status. Ulipristal acetate (UPA) have been shown to be effective
in bleeding control, induction of amenorrhea and fibroid reduction when compared to GnRHa,
with fewer side effects as it maintains estradiol at mid-follicular phase levels.
Pre-surgical UPA treatment allows recovery of Hb levels and reduction in fibroid size,
allowing better minimally invasive surgery procedures. On selected patients, long-term
intermittent treatment with UPA offers an alternative to surgery allowing patients to reach
menopause status without surgery.
In February 2018, the European Medicines Agency (EMA) announced temporary restrictive
measures to UPA treatment as 8 cases of severe liver injury were potentially linked to UPA
administration. After the Pharmacovigilance Risk Assessment Committee (PRAC) evaluation
concluded, the association between UPA and drug induced liver injury (DILI) was neither
confirmed nor excluded. As a conclusion, the EMA stated that the benefits of UPA for the
treatment of symptomatic uterine fibroids clearly outweigh the risks, but risk-minimization
measures were needed in order to avoid the rare but serious possible liver injury.
In this work, the investigators evaluated evaluate whether changes in transaminase levels or
other DILI markers occur in patients receiving UPA in the study center.
MATERIAL AND METHODS Retrospective observational study to assess the variations of liver
blood test parameters during UPA treatment for symptomatic uterine fibroids. The study is
approved by the ethics committee of the study site and will be conducted in accordance with
the principles of the International Conference on Harmonization-Good Clinical Practice
(ICH-GCP) guidelines Investigators will include all women who had completed a full 12-week
treatment course of UPA for symptomatic uterine fibroids since September 2018. All patients
will provide written informed consent. As stated by EMA recommendations, all patients will
perform a blood test including liver parameters (AST, ALT, AF, GGT, bilirubin) before
initiating the treatment, monthly during the 12-week treatment course, and an additional test
2-4 weeks after ending treatment. All data will be collected in an anonymized database with
restricted access to investigators
