Letrozole add-on in the Treatment of Cesarean Scar Pregnancy

Evaluation of the Therapeutic Effect of Adding Letrozole to the Protocol of Combined Treatment of Cesarean Scar Pregnancy

It is hypothesized that the inhibition of estradiol production by letrozole may interfere with physiological effects of progesterone necessary to maintain the pregnancy. There is no reference treatment of cesarean scar pregnancy (CSP) as the limited number of cases precludes the extrapolation of results. In our center we successfully use two-step treatment with methotrexate (MTX) followed by hysteroscopic removal of products of conception (POC). The time in between is needed to achieve a decrease in the trophoblast's vital potential (B-hCG fall) and its vascularization. Additional administration of letrozole could further reduce the vital potential of the pregnancy, eliminating the need for another dose of MTX, resulting in faster healing and lower rate of complications.

Study Overview

• Status: Completed
• Conditions: Cesarean Scar Pregnancy
• Intervention / Treatment: Drug: MTX monotherapy; Drug: MTX + letrozole add-on

Detailed Description

A prospective cohort study is conducted among women with cesarean scar pregnancy (CSP). Women with increasing B-human chorionic gonadotropin (B-hCG) concentrations are included.

Two study arms were planned:

• women treated with a single dose of 100 mg MTX intravenously and 50 mg MTX in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH)
• women treated with a single dose of 100 mg MTX intravenously and 50 mg MTX in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH) with additional use of letrozole 5 mg orally (from day 0) for 10 days.

Blood parameters (B-hCG, hemoglobin, total blood count, creatinine, urea, alanine/aspartate transaminase, gamma-glutamyltransferase, bilirubin) were tested on days 0,4,7, followed by B-hCG concentration measurement every 7 days until surgery. After obtaining satisfactory decrease in B-hCG and POC vascularization, women underwent hysteroscopic evacuation of POC. Blood loss parameters, frequency of conversion from hysteroscopy to laparoscopy and laparotomy were measured.

The women were given the option to choose the treatment used in the study. All enrolled women gave informed written consent to participate in the study.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Krakow, Poland, 31-501
    • Jagiellonian University Medical College, Department of Gynecology and Obstetrics, Clinic of Gynecological Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• CSP confirmed on pelvic ultrasound
• consent of the Bioethics Committee for termination of CSP
• increasing B-hCG concentrations

Exclusion Criteria:

• heterotopic pregnancy
• decreasing B-hCG concentrations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MTX in monotherapy; Combined treatment with MTX followed by hysteroscopic evacuation of POC	Drug: MTX monotherapy; MTX in a single dose of 100 mg intravenously and 50 mg in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH), and subsequent hysteroscopic evacuation of products of conception (POC)
Active Comparator: MTX + letrozole add-on; Combined treatment with MTX + letrozole add-on followed by hysteroscopic evacuation of POC	Drug: MTX + letrozole add-on; MTX in a single dose of 100 mg intravenously and 50 mg in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH) + Letrozole in a daily dose of 5 mg (2 x 2.5 mg) orally for 10 days from day 0, and subsequent hysteroscopic evacuation of products of conception (POC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood loss during the procedure expressed as a decrease in hemoglobin concentration	Decrease in hemoglobin concentration in g/dl on day 1 after the procedure compared to the pre-procedure concentration	up to 6 months
Blood loss volume during the procedure expressed in volume units	The volume of blood lost during the procedure in ml	up to 6 months
Conversion rate from hysteroscopy to laparoscopy or laparotomy due to due to hemorrhage	Percentage (%) of conversion from hysteroscopy to laparoscopy or laparotomy due to hemorrhage	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of treatment on liver function (alanine transaminase)	Changes in the concentrations of alanine transaminase (IU/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on liver function (aspartate transaminase)	Changes in the concentrations of aspartate transaminase (IU/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on liver function (gamma-glutamyltransferase)	Changes in the concentrations of gamma-glutamyltransferase (IU/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on bone marrow function (red blood cells)	Change in red blood count (T/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on bone marrow function (white blood cells)	Change in white blood count (G/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on bone marrow function (platelets)	Change in platelet count (G/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on liver function (serum total bilirubin)	Changes in the concentrations of serum total bilirubin (mg/dl) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on kidneys function (urea)	Changes in the concentrations of serum urea (mmol/l) in the course of treatment (day 0,4,7)	up to 6 months
The effect of treatment on kidneys function (creatinine)	Changes in the concentrations of serum and creatinine (mg/dl) in the course of treatment (day 0,4,7)	up to 6 months

Collaborators and Investigators

• Sponsor: Jagiellonian University
• Investigators: Study Chair: Robert Jach, Prof., Ph.D., Jagiellonian University; Principal Investigator: Iwona M. Gawron, M.D., Ph.D., Jagiellonian University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: April 15, 2023
• First Submitted That Met QC Criteria: April 29, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: operative hysteroscopy; cesarean scar pregnancy
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: 1072.6120.46.2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No