Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Liver Safety Assessment During Ulipristal Acetate Treatment for Uterine Fibroids (LISA) (LISA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04004884
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : July 9, 2019
Sponsor:
Information provided by (Responsible Party):
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Brief 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.


Condition or disease Intervention/treatment
Leiomyoma, Uterine Liver Injury Treatment Side Effects Drug: Ulipristal Acetate

Detailed 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

Layout table for study information
Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Liver Safety Assessment During Ulipristal Acetate Treatment for Uterine Fibroids
Actual Study Start Date : May 23, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
UPA Treatment
Women who had completed a full 12-week treatment course of Ulipristal Acetate for symptomatic uterine fibroids since September 2018
Drug: Ulipristal Acetate
Assess the variations of liver blood test parameters during UPA treatment for symptomatic uterine fibroids
Other Name: Esmya




Primary Outcome Measures :
  1. Transaminase levels [ Time Frame: 12 weeks ]
    Variations on AST or ALT blood levels during UPA treatment course.


Secondary Outcome Measures :
  1. Gamma Glutamyl Transferase (GGT) levels [ Time Frame: 12 weeks ]
    Variations on GGT blood levels during UPA treatment course.

  2. Bilirubin levels [ Time Frame: 12 weeks ]
    Variations on bilirubin blood levels during UPA treatment course.

  3. Alkaline phosphatase (AF) levels [ Time Frame: 12 weeks ]
    Variations on AF blood levels during UPA treatment course.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All women who had completed a full 12-week treatment course of UPA for symptomatic uterine fibroids since September 2018.
Criteria

Inclusion Criteria:

  • Age 18-55 years
  • Symptomatic uterine fibroids
  • Being prescribed UPA as a treatment for symptomatic uterine fibroids according to regular practice.

Exclusion Criteria:

  • Pregnancy
  • Breastfeeding
  • Previous or active hepatic disease
  • Transaminase (AST,ALT) blood levels higher than 3 times the upper normal limit.
  • Bilirubin blood levels higher than 3 times the upper normal limit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04004884


Contacts
Layout table for location contacts
Contact: Josep Estadella 0034 935537041 jestadella@santpau.cat

Locations
Layout table for location information
Spain
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08027
Contact: Josep Estadella    0034 935537041    jestadella@santpau.cat   
Principal Investigator: Josep Estadella         
Sponsors and Collaborators
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Investigators
Layout table for investigator information
Principal Investigator: Josep Estadella Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Layout table for additonal information
Responsible Party: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier: NCT04004884    
Other Study ID Numbers: IIBSP-ULI-2019-05
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:
Ulipristal Acetate
Selective Progesterone Receptor Modulators
Leiomyoma
Liver injury
Additional relevant MeSH terms:
Layout table for MeSH terms
Leiomyoma
Myofibroma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Connective Tissue Diseases
Ulipristal acetate
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs