Letrozole in Tubal Ectopic Pregnancy

NCT04341545 | Unknown Phase 3 DMC

• 1 other identifier: UW 20-005
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-centred randomized controlled trial on the addition of letrozole in the medical management of tubal ectopic pregnancies. Tubal ectopic pregnancies are abnormal pregnancies in the Fallopian tube, rather than in the womb. They occurred in around 1-2% of all pregnancies. Methotrexate (MTX) given by the intramuscular route i.e. systemic, a commonly used drug for cancer , was a widely used alternative for management for unruptured tubal ectopic pregnancies and was recommended as first line treatment for selected women. Letrozole, aromatase inhibitor, can suppose oestradiol level. Combination of letrozole with misprostol has shown to improve the complete abortion rate in miscarriage. As a result, addition of letrozole may cause a higher success rate in the medical treatment of ectopic pregnancy. As the evidence of combination of MTX and letrozole in tubal ectopic pregnancies is not available, the objective of the present study is to evaluate the efficacy of combination of MTX and letrozole compared to MTX alone in women with tubal ectopic pregnancies.

Conditions

Tubal Pregnancy

Keywords

Tubal ectopic pregnancy; Methotrexate; Letrozole

Outcome Measures

Primary Outcomes (1)

• Treatment success

  Proportion of women with treatment success defined as normalization of serum hCG level \<10IU/L without additional medical or surgical intervention

  2 months

Secondary Outcomes (4)

• hCG normalization duration

  2 months

• Number of participants experienced side effects

  2 months

• Duration of hospitalization

  2 months

• Participant satisfaction: proportion of women who would recommend this treatment to a friend

  2 months

Study Arms (2)

Letrozole

EXPERIMENTAL

Participants will be given letrozole 10mg daily for one week after standard medical management for tubal ectopic pregnancy by methotrexate injection. Subsequently they will receive the standard management for medical management of tubal ectopic prengnacies.

Drug: Letrozole tablets

Placebo

PLACEBO COMPARATOR

Participants will be given identical looking placebo for one week and receive the same standard management for medical management of tubal ectopic pregnancies.

Other: Placebos

Interventions

Placebos OTHER

Placebo 4 tablets a day for one week.

Placebo

Letrozole tablets DRUG

Letrozole 10mg daily for one week.

Also known as: Letrozole

Letrozole

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Ectopic pregnancies studied
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of heterogenous adnexal mass on USG suggestive of tubal ectopic pregnancy with hCG level \>=1500 IU/L and \<= 5000 IU/L
• Absence of fetal heart pulsation
• Mean diameter of adnexal mass \<= 3.5cm
• Haemodynamically stable
• No significant abdominal pain

You may not qualify if:

• Presence of significant amount of free fluid in pelvis
• Allergic to MTX
• Deranged liver function test (AST/ ALT or GGT \>= 2 upper limit of normal)
• Deranged renal function test (eGFR \<= 45ml/min)
• Heterotopic pregnancies

Sponsors & Collaborators

• Queen Mary Hospital, Hong Kong: lead
• Kwong Wah Hospital: collaborator
• Princess Margaret Hospital, Hong Kong: collaborator
• Pamela Youde Nethersole Eastern Hospital, Hong Kong: collaborator
• Queen Elizabeth Hospital, Hong Kong: collaborator
• Prince of Wales Hospital, Shatin, Hong Kong: collaborator

Study Sites (1)

Department of Obstetrics and Gynaecology, Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (8)

• Panelli DM, Phillips CH, Brady PC. Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review. Fertil Res Pract. 2015 Oct 15;1:15. doi: 10.1186/s40738-015-0008-z. eCollection 2015.

  PMID: 28620520 BACKGROUND

• 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.

  PMID: 27813249 BACKGROUND

• Odejinmi F, Huff KO, Oliver R. Individualisation of intervention for tubal ectopic pregnancy: historical perspectives and the modern evidence based management of ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:69-75. doi: 10.1016/j.ejogrb.2016.10.037. Epub 2016 Oct 29.

  PMID: 27940397 BACKGROUND

• National Collaborating Centre for Ws, Children's H. National Institute for Health and Clinical Excellence: Guidance. Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. London: Rcog National Collaborating Centre for Women's and Children's Health.; 2012.

  BACKGROUND

• Shi L, Shi SQ, Given RL, von Hertzen H, Garfield RE. Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy. Steroids. 2003 Nov;68(10-13):1077-84. doi: 10.1016/j.steroids.2003.09.002.

  PMID: 14668001 BACKGROUND

• Albrecht ED, Aberdeen GW, Pepe GJ. The role of estrogen in the maintenance of primate pregnancy. Am J Obstet Gynecol. 2000 Feb;182(2):432-8. doi: 10.1016/s0002-9378(00)70235-3.

  PMID: 10694348 BACKGROUND

• Lee VCY, Ng EHY, Yeung WSB, Ho PC. Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. Obstet Gynecol. 2011 Feb;117(2 Pt 1):317-323. doi: 10.1097/AOG.0b013e3182073fbf.

  PMID: 21252745 BACKGROUND

• Lee VC, Tang OS, Ng EH, Yeung WS, Ho PC. A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days. Contraception. 2011 Jan;83(1):62-7. doi: 10.1016/j.contraception.2010.05.014. Epub 2010 Jun 23.

  PMID: 21134505 BACKGROUND

MeSH Terms

Conditions

Pregnancy, Tubal

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Pregnancy, Ectopic; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ernest H.Y. Ng, MD

  The University of Hong Kong

  STUDY DIRECTOR

Central Study Contacts

Evelyn Wong, MBBS

CONTACT

22554517; evelynwong.ew@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The identical looking placebo will be given. A computer generated sequence will be created. The sequence will be sealed in consecutively concealed opaque envelopes. Both the participant/ care provider/ investigator and outcomes assessor will blinded to the group assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate consultant

Model Details: Participants will be randomized into either receive letrozole or placebo capsules.

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 10, 2020
• Study Start: December 1, 2020
• Primary Completion: December 30, 2024
• Study Completion: March 31, 2025
• Last Updated: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)