Sequential vs. Combined Letrozole and Methotrexate for Tubal Ectopic Pregnancy.

NCT07842796 | Active Not Recruiting Phase 2

• 1 other identifier: RC: 1/12/2024
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates two medical strategies designed to minimize surgical intervention and reduce methotrexate (MTX) exposure in women with undisturbed tubal ectopic pregnancy (TEP). Participants with undisturbed TEP and pre-treatment serum $\\beta$-hCG levels $\<3500\\text{ IU/L}$ are randomized to receive either a sequential regimen (initial letrozole monotherapy, reserving MTX only for treatment non-responders) or a combined regimen (simultaneous letrozole and single-dose MTX from day one). The study aims to compare the overall success rate of resolving TEP without emergency surgery, as well as the ability of the sequential approach to avoid MTX administration altogether.

Conditions

Ectopic Pregnancy

Outcome Measures

Primary Outcomes (1)

• Letrozole Standalone Success Rate

  Resolution of tubal ectopic pregnancy (confirmed by TVU and beta-hCG \< 15 IU/L) achieved via Letrozole monotherapy without requiring Methotrexate or surgical intervention

  19 days post-initiation oftreatment treatment.

Secondary Outcomes (1)

• Avoidance of Surgery

  19 days post-initiation oftreatment treatment.

Study Arms (2)

Sequential Protocol

ACTIVE COMPARATOR

Participants in this arm initially receive oral Letrozole at a dose of 5 mg daily (administered as two 2.5 mg film-coated tablets once daily) for 4 consecutive days. On Day 4, serum beta-hCG levels are evaluated to specify if rescue needed we will give a single intramuscular rescue injection of Methotrexate (50mg/m) while continuing Letrozole for an additional 7 days.

Drug: Letrozole; Drug: Methotrexate

Combined Protocol

ACTIVE COMPARATOR

Participants in this arm receive simultaneous dual drug therapy starting on Day 1

Drug: Letrozole; Drug: Methotrexate

Interventions

Letrozole DRUG

Oral Letrozole 5 mg/day (2 times 2.5{ mg} tablets daily) for 4 days. If serum beta-hCG drops by \>10% on Day 4, Letrozole is continued.

Combined Protocol; Sequential Protocol

Methotrexate DRUG

A single intramuscular injection of Methotrexate (50mg/m) is administered as rescue therapy, If beta-hCG drop is \<10 on Day 4,

Combined Protocol; Sequential Protocol

Eligibility Criteria

• Age: 24 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis: Confirmed undisturbed/intact unilateral tubal ectopic pregnancy (TEP) presenting with lower abdominal pain and absence of vaginal bleeding.
• Pre-treatment beta-hCG Level: Baseline serum beta-human chorionic gonadotropin (beta-hCG) level of less than 3,500 IU/L.
• Ectopic Mass Dimensions: Gestational mass with a maximum diameter of less than 3.5 cm measured on transvaginal ultrasonography (TVU).
• Ultrasound Integrity: Absence of transvaginal ultrasound features indicating hemoperitoneum or active intraperitoneal bleeding.
• Informed Consent: Willingness to comply with follow-up schedules and provision of written informed consent.

You may not qualify if:

• Disturbed Ectopic Pregnancy: Clinical, laboratory, or ultrasound evidence of tubal rupture, hemoperitoneum, or active intra-abdominal hemorrhage.
• Elevated beta-hCG: Serum beta-hCG levels equal to or exceeding 3,500 IU/L at baseline.
• Mass Size: Gestational mass diameter \> 3.5 cm.
• Contraindications to Methotrexate or Letrozole: Known hypersensitivity or contraindications to therapy (e.g., active hepatic, renal, or hematological dysfunctions).
• Non-compliance: Inability or unwillingness to comply with the serial post-treatment beta-hCG monitoring and follow-up protocol.

Sponsors & Collaborators

• Benha University: lead

Study Sites (1)

Benha university

Banhā, El Qalyoubia, 13511, Egypt

Location

MeSH Terms

Conditions

Pregnancy, Ectopic

Interventions

Letrozole; Methotrexate

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obstetrics & Gynecology, Faculty of Medicine, Benha University

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 25, 2026
• Study Start: December 15, 2024
• Primary Completion: July 10, 2026
• Study Completion (Estimated): December 12, 2026
• Last Updated: September 25, 2026

Record last verified: 2026-09

Locations

EG (1)