Use of Letrozole for Ectopic Pregnancy

Ectopic Pregnancy Clinical Trial

— EcZOL  

Official title:

Use of Letrozole in the Treatment of Early Ectopic Pregnancy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06354439
• Other study ID #: 77015224.6.1001.5327
• Status: Recruiting
• Phase: Phase 4
• Start date: March 27, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Hospital de Clinicas de Porto Alegre
• Contact: Ricardo F Savaris, MD, PhD
• Phone: +55 51 997781966
• Email: rsavaris[@]hcpa.edu.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized clinical trial using oral letrozole 10mg/day for 7 days, for treating early cases of ectopic pregnancy, compared to intramuscular methotrexate

Description:

This is a multicenter randomized clinical trial on the use of letrozole in the medical treatment of tubal ectopic pregnancy. Tubal ectopic pregnancy is an abnormal pregnancy in the fallopian tube. They occurred in about 8% of all pregnancies presenting to the emergency department. Methotrexate (MTX), administered systemically (intramuscularly), is a widely used medication for the treatment of unruptured tubal ectopic pregnancies and has been recommended as first-line treatment for early cases of ectopic pregnancy.

Letrozole is an aromatase inhibitor and can suppress estradiol levels. Some recent studies have shown that its use can be applied in cases of ectopic pregnancy.

The aim of this non-inferiority clinical trial is to verify that letrozole treatment is non-inferior to methotrexate treatment in women with early ectopic pregnancy who are hemodynamically stable.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years or older

• Diagnosis of ectopic pregnancy

• Desire for reproduction

• Ease of return

• Undetermined pregnancy location with abnormal hCG growth

• Presence of a heterogeneous adnexal mass on pelvic ultrasound suggestive of a tubal ectopic pregnancy with an hCG level = 3000 mIU/ml

• Absence of fetal cardiac activity

• Average diameter of the adnexal mass = 3.5 cm

• Hemodynamically stable

• No significant abdominal pain (i.e, < 6 on a visual analog scale)

Exclusion Criteria:

• Presence of a significant amount of free fluid in the pelvis (as assessed by the ultrasound technician)

• Allergy to methotrexate or letrozole

• A reduction in ß-hCG = 50% in 2 measurements with 48 hours between them or

= 85% in 4 days, or = 95% in 7 days before randomization

• Abnormal liver function test (Alanine transaminase (ALT) = 2 times the upper limit of normal)

• Abnormal renal function test (glomerular filtration rate = 45 ml/min)

• Hemoglobin <10 g/dl

• Platelets <120.000/ml

• Presence of heterotopic pregnancy

• Do not wish to participate in the study.

Related Conditions & MeSH terms

• Ectopic Pregnancy
• Pregnancy, Ectopic

Intervention

Drug:
• Letrozole tablets
10 mg of letrozole PO for 7 days
• Methotrexate Sodium
100 mg of methotrexate IM, single dose

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

References & Publications (12)

Alabiad MA, Said WMM, Gad AH, Sharaf ElDin MTA, Khairy DA, Gobran MA, Shalaby AM, Samy W, Abdelsameea AA, Heraiz AI. Evaluation of Different Doses of the Aromatase Inhibitor Letrozole for the Treatment of Ectopic Pregnancy and Its Effect on Villous Trophoblastic Tissue. Reprod Sci. 2022 Oct;29(10):2983-2994. doi: 10.1007/s43032-022-00993-0. Epub 2022 Jun 14. — View Citation

Auger N, Ayoub A, Wei SQ. Letrozole: future alternative to methotrexate for treatment of ectopic pregnancy? Fertil Steril. 2020 Aug;114(2):273-274. doi: 10.1016/j.fertnstert.2020.04.063. Epub 2020 Jul 1. No abstract available. — View Citation

Bouyer J, Coste J, Fernandez H, Pouly JL, Job-Spira N. Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod. 2002 Dec;17(12):3224-30. doi: 10.1093/humrep/17.12.3224. — View Citation

Casper RF, Mitwally MF. Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clin Obstet Gynecol. 2011 Dec;54(4):685-95. doi: 10.1097/GRF.0b013e3182353d0f. — View Citation

Diagnosis and Management of Ectopic Pregnancy: Green-top Guideline No. 21. BJOG. 2016 Dec;123(13):e15-e55. doi: 10.1111/1471-0528.14189. Epub 2016 Nov 3. No abstract available. Erratum In: BJOG. 2017 Dec;124(13):e314. — View Citation

Farquhar CM. Ectopic pregnancy. Lancet. 2005 Aug 13-19;366(9485):583-91. doi: 10.1016/S0140-6736(05)67103-6. — View Citation

Link CA, Maissiat J, Mol BW, Barnhart KT, Savaris RF. Diagnosing ectopic pregnancy using Bayes theorem: a retrospective cohort study. Fertil Steril. 2023 Jan;119(1):78-86. doi: 10.1016/j.fertnstert.2022.09.016. Epub 2022 Oct 26. — View Citation

Lipscomb GH, Gomez IG, Givens VM, Meyer NL, Bran DF. Yolk sac on transvaginal ultrasound as a prognostic indicator in the treatment of ectopic pregnancy with single-dose methotrexate. Am J Obstet Gynecol. 2009 Mar;200(3):338.e1-4. doi: 10.1016/j.ajog.2008.12.006. — View Citation

Mitwally MF, Hozayen WG, Hassanin KMA, Abdalla KA, Abdalla NK. Aromatase inhibitor letrozole: a novel treatment for ectopic pregnancy. Fertil Steril. 2020 Aug;114(2):361-366. doi: 10.1016/j.fertnstert.2020.04.001. Epub 2020 Jul 1. — View Citation

Qian X, Li Z, Ruan G, Tu C, Ding W. Efficacy and toxicity of extended aromatase inhibitors after adjuvant aromatase inhibitors-containing therapy for hormone-receptor-positive breast cancer: a literature-based meta-analysis of randomized trials. Breast Cancer Res Treat. 2020 Jan;179(2):275-285. doi: 10.1007/s10549-019-05464-w. Epub 2019 Oct 12. — View Citation

Rezaei Z, Ghaemi M, Feizabad E, Ghavami B, Akbari Asbagh F, Davari Tanha F, Ebrahimi M, Khalaj Sereshki Z. The Effective Role of Adding Letrozole to Methotrexate in the Management of Tubal Ectopic Pregnancies, a Randomized Clinical Trial. Iran J Pharm Res. 2021 Fall;20(4):378-384. doi: 10.22037/ijpr.2021.115659.15461. — View Citation

van Mello NM, Mol F, Ankum WM, Mol BW, van der Veen F, Hajenius PJ. Ectopic pregnancy: how the diagnostic and therapeutic management has changed. Fertil Steril. 2012 Nov;98(5):1066-73. doi: 10.1016/j.fertnstert.2012.09.040. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	levels of beta fraction of human chorionic gonadotropin (beta-hCG)	On day 4 (D4) and 7(D7), beta-hCG levels will be measured. If a reduction equal or above 15% between D4 and D7 were observed, serum beta-hCG will be measured until reach levels < 5 milli-International unit per milliliter (mIU/ml).	weekly after the first day of intervention until reaching levels of beta-hCG below 5 milli-International unit per milliliter (assessed up to 5 months)"