Clinical trial NCT05203562: Letrozole as a Prophylaxis From GTN for Complete Mole Patients
Official title: The Prophylactic Role of Aromatase Inhibitor Letrozole in Decreasing the Incidence of Gestational Trophoblastic Neoplasia in Patients With Complete Hydatidiform Mole
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Gestational Trophoblastic Disease
Keywords: Aromatase Inhibitor; Letrozole; GTN; Complete Mole
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2022-01-24
Enrollment: 200
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Prophylactic use of aromatase inhibitor is effective in decreasing the incidence of Gestational Trophoblastic Neoplasia (GTN) in patients with complete hydatidiform mole (CHM)

Detailed description: Management of hydatidiform mole is usually evacuation followed by β-hcg surveillance to early detect cases of GTN . The risk of developing GTN is reported to be 16% to 20% in women with CHM . GTN is a potentially life-threatening malignancy but has an excellent cure rate. Trials were conducted to assess the role of prophylactic chemotherapy to prevent the development of GTN. In addition to their side effects, a meta-analysis concluded that there is insufficient evidence to support the use of prophylactic chemotherapy in clinical practice. Third-generation aromatase inhibitors such as letrozole have been shown to successfully block estrogen production in women of reproductive age. Their safety, high tolerability, low cost, and associated minimal adverse effects have all been established over several decades of clinical use and recently used successfully alone in the medical treatment of ectopic pregnancy making marked degenerative effects on the placenta.

The study hypothesizes that by inhibiting the estrogen synthetase (the aromatase enzyme) progesterone would not exert its physiological role in maintaining early pregnancy including complete hydatidiform mole. Thus, using a prophylactic aromatase inhibitor after CHM may have a role in the prevention of GTN and more effective clearance of β-hcg.

Rational GTN is a potentially life-threatening malignancy. The risk of progression of CHM to GTN is 20%. Prophylactic use of aromatase inhibitor may decrease the incidence of GTN.

Research question:

Is prophylactic use of aromatase inhibitor effective in decreasing the incidence of GTN in patients with CHM

Hypothesis Prophylactic use of aromatase inhibitor is effective in decreasing the incidence of GTN in patients with CHM

Aim of this work The study aims at figuring out whether prophylactic use of aromatase inhibitor is effective in decreasing the incidence of GTN in patients with CHM.

OBJECTIVES

* To assess the incidence of GTN after the evacuation of CHM without prophylactic use of aromatase inhibitor.
* To assess the incidence of GTN after the evacuation of CHM without prophylactic use of aromatase inhibitor.
* To assess the side effects of aromatase inhibitor when used as a prophylaxis against GTN development in CHM cases.

PATIENTS AND METHODS

Technical design:

* Setting: Department of Obstetrics and Gynecology
* Sample size: 200 patients diagnosed to have CHM by ultrasound and confirmed by histopathological examination.

Operational design:

* Type of the study: a randomized controlled trial.
* Steps of performance and techniques that will be used

women included in the study will be subjected to the following

Preoperative

1. Complete history taking.
2. General and abdominal examination.
3. Routine preoperative laboratory investigations.
4. Ultrasound to diagnose complete hydatidiform mole.
5. Measurement of β-hcg level. Intraoperative

   * Evacuation of CHM using Suction curettage.
   * Tissues obtained during an evacuation will be sent for histological assessment. Post-operative
   * Women will be randomized classified into two groups
   * Control group I: Conservative follow up
   * Prophylactic letrozole group II 5-mg Letrozole will be administered as two 2.5-mg tablets every day for 10 days.
   * All Patients will receive instruction to return for β-hcg follow up which will be done weekly till complete resolution then monthly for 6 months.
   * Participants will be advised to receive contraception during the follow-up period.
   * The patients who will develop GTN in either group will be picked up and the incidence of GTN will be calculated in each group.

Eligibility criteria: Inclusion Criteria:

* Women were diagnosed to have CHM by ultrasound and confirmed by histopathological examination

Exclusion Criteria:

* Metastatic disease associated with HM at presentation, in which situation chemotherapy, rather than prophylactic treatment, as prescribed,
* Late diagnosis of CHM made only by histological examination of curetted material
* Uterine evacuation at another hospital and patient seen at the optimum patient care only for follow up

Primary outcomes:
measure: (β-hCG) level
timeFrame: at the first day of evacuation
measure: (β-hCG) level
timeFrame: one month after evacuation
measure: (β-hCG) level
timeFrame: two months after evacuation
measure: (β-hCG) level
timeFrame: three months after evacuation
measure: (β-hCG) level
timeFrame: four months after evacuation
measure: (β-hCG) level
timeFrame: Five months after evacuation
measure: (β-hCG) level
timeFrame: Six months after evacuation
Secondary outcomes:
Other outcomes:
Locations:
city: Zagazig
country: Egypt
facility: Mohamed ALI Alabiad
state: Sharkia
Study officials:
affiliation: Zagazig University
name: Mohamed A Alabiad, MD
role: PRINCIPAL_INVESTIGATOR
References: