Letrozole in Tubal Ectopic Pregnancy

NCT ID: NCT04341545

Last Updated: 2023-04-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-01

Study Completion Date

2025-03-31

Brief Summary

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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.

Detailed Description

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Tubal ectopic pregnancies occur in around 1-2% of all pregnancies. Traditionally, surgery with salpingectomy was the mainstay of treatment; however, it comes with anaesthetic and operatives risks in addition to an increased cost for operative procedures. In recent years, systemic methotrexate (MTX), a dihydrofolate reductase inhibitor, has been a widely used alternative for management for unruptured tubal ectopic pregnancies. The success rate of systemic MTX at a doses of 50mg/m2 body surface area is around 70% which ranges from 65 to 95%, depending greatly on the level of human chorionic gonadotrophin (hCG), the size of adnexal mass and presence of fetal heart pulsation.

Use of systemic MTX as the first-line management has been proposed for women with unruptured ectopic pregnancy where the adnexal mass is smaller than 35mm, serum hCG level is less than 5000 IU/l and fetal heartbeat is absent.

Letrozole is a third generation non-steroidal reversible aromatase inhibitor. It can suppress oestradiol level up to 95% to 99% after administration according to pharmacodynamics and pharmacokinetics studies. Oestrogen is important in the support of early pregnancy, other than progesterone with well-known pivotal effect on the maintenance of early pregnancy.

Animal studies showed the combination of mifepristone and letrozole worked synergistically and induced almost 100% termination of pregnancies in rats. Letrozole induced 50% miscarriage rate in pregnant baboons. Letrozole combined with vaginal misoprostol regimen was associated with a higher complete abortion rate than misoprostol alone in pregnancies up to 63 days.

The use of letrozole in ectopic pregnancy has never been explored. It is hypothesized that letrozole can suppress serum oestradiol level, which in turn, may cause failure of pregnancy in ectopic pregnancy. The aim of this study is to investigate the clinical effectiveness of letrozole in addition to MTX in the medical treatment of ectopic pregnancy.

Conditions

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Tubal Pregnancy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomized into either receive letrozole or placebo capsules.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Letrozole

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.

Group Type EXPERIMENTAL

Letrozole tablets

Intervention Type DRUG

Letrozole 10mg daily for one week.

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type OTHER

Placebo 4 tablets a day for one week.

Interventions

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Placebos

Placebo 4 tablets a day for one week.

Intervention Type OTHER

Letrozole tablets

Letrozole 10mg daily for one week.

Intervention Type DRUG

Other Intervention Names

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Letrozole

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Kwong Wah Hospital

OTHER

Sponsor Role collaborator

Princess Margaret Hospital, Hong Kong

OTHER_GOV

Sponsor Role collaborator

Pamela Youde Nethersole Eastern Hospital, Hong Kong

UNKNOWN

Sponsor Role collaborator

Queen Elizabeth Hospital, Hong Kong

OTHER

Sponsor Role collaborator

Prince of Wales Hospital, Shatin, Hong Kong

OTHER

Sponsor Role collaborator

Queen Mary Hospital, Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Evelyn Wong

Associate consultant

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ernest H.Y. Ng, MD

Role: STUDY_DIRECTOR

The University of Hong Kong

Locations

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Department of Obstetrics and Gynaecology, Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status RECRUITING

Countries

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Hong Kong

Central Contacts

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Evelyn Wong, MBBS

Role: CONTACT

Facility Contacts

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Karen Chan, Prof

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 28620520 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27813249 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27940397 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 14668001 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10694348 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21252745 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21134505 (View on PubMed)

Other Identifiers

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UW 20-005

Identifier Type: -

Identifier Source: org_study_id

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