Monotherapy With Letrozole in Tubal Pregnancy

Study Overview
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Brief Summary
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It is hypothesized that the inhibition of estradiol production by letrozole may interfere with physiological effects of progesterone necessary to maintain the pregnancy. Treatment of tubal pregnancy with letrozole would allow to avoid the adverse effects of methotrexate (MTX) in women refusing surgery. The aim was to compare the effectiveness of letrozole with MTX in the management of tubal pregnancy.

Detailed Description
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A prospective cohort study is conducted among women with tubal pregnancy. Women with increasing B-human chorionic gonadotropin (B-hCG) concentrations are included. Two study arms were planned: i) women treated with MTX: MTX in a single dose of 100 mg intravenously on day 0; ii) women treated with letrozole: letrozole at a daily dose of 5 mg orally for 10 days from day 0. The inclusion criteria included B-hCG concentration up to 3000 mIU/ml and no contraindications to conservative treatment. Women who did not meet criteria for conservative treatment were excluded. Blood parameters (B-hCG, hemoglobin, creatinine, urea, alanine/aspartate transaminase, gamma-glutamyltransferase, bilirubin) were tested on days 0,4,7. Cases of treatment failure were counted, i.e. the need to perform laparoscopy due to tubal pregnancy rupture, pain, increase in B-hCG concentration. 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.

Official Title
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Management of Tubal Pregnancy With Off-label Use of Letrozole in Monotherapy

Conditions
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Tubal Pregnancy Unruptured

Intervention / Treatment
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* Drug: Letrozole as monotherapy
* Drug: MTX as monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: tubal pregnancy confirmed on pelvic ultrasound increasing serum B-hCG concentrations in at least two subsequent measures serum B-hCG concentration ≤ 3000 mIU/ml Exclusion Criteria: free fluid in lesser pelvis on pelvic ultrasound positive fetal heartbeat on pelvic ultrasound abdominal pain heterotopic pregnancy contraindications to MTX

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tubal pregnancy treated with MTX<br>MTX in a single dose of 100 mg intravenously on day 0 | Drug: MTX as monotherapy<br>* MTX in a single dose of 100 mg intravenously on day 0<br>|
| Active Comparator: Tubal pregnancy treated with letrozole<br>Letrozole in a daily dose of 5 mg (2 x 2.5 mg) orally for 10 days from day 0 | Drug: Letrozole as monotherapy<br>* Letrozole 5 mg daily orally for 10 days from day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effectiveness of the treatment | Conversion rate to laparoscopy due to tubal rupture, pain, serum B-hCG increase in the course of treatment | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of treatment on bone marrow function (hemoglobin) | Changes in hemoglobin concentration (g/dl) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on bone marrow function (red blood cells) | Changes in red blood cell 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) | Changes 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) | Changes 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 (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 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 kidney 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 kidney function (creatinine) | Changes in the concentrations of serum creatinine (mg/dl) in the course of treatment (day 0,4,7) | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tubal pregnancy, Methotrexate, Letrozole