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Letrozole in Tubal Ectopic Pregnancy

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ClinicalTrials.gov Identifier: NCT04341545
Recruitment Status : Not yet recruiting
First Posted : April 10, 2020
Last Update Posted : April 14, 2020
Sponsor:
Information provided by (Responsible Party):
Lui Man Wa, Queen Mary Hospital, Hong Kong

Brief Summary:

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 efficacy of combination of MTX and letrozole in women with tubal ectopic pregnancies


Condition or disease Intervention/treatment Phase
Tubal Pregnancy Other: Placebos Drug: Letrozole tablets Phase 3

Detailed Description:

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 the medical treatment of ectopic pregnancy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized into either receive letrozole or placebo capsules.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial on Use of Letrozole in the Medical Management of Tubal Ectopic Pregnancies
Estimated Study Start Date : July 1, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: 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.
Drug: Letrozole tablets
Letrozole 10mg daily for one week.
Other Name: Letrozole

Placebo Comparator: Placebo
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
Placebo 4 tablets a day for one week.




Primary Outcome Measures :
  1. Treatment success [ Time Frame: 2 months ]
    Proportion of women with treatment success defined as normalization of serum hCG level <10IU/L without additional medical or surgical intervention


Secondary Outcome Measures :
  1. hCG normalization duration [ Time Frame: 2 months ]
    Duration of time until hCG normalization measured in days

  2. Mass resolution [ Time Frame: 2 months ]
    Duration of resolution of adnexal mass

  3. Number of participants experienced side effects [ Time Frame: 2 months ]
    Side effects after letrozole

  4. Duration of hospitalization [ Time Frame: 2 months ]
    Duration of hospitalization

  5. Participant satisfaction: proportion of women who would recommend this treatment to a friend [ Time Frame: 2 months ]
    Treatment satisfaction measured as proportion of women who would recommend this treatment to a friend



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Ectopic pregnancies studied
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Tubal ectopic pregnancy suggested by presence of a heterogenous adnexal mass with suboptimal rise of hCG i.e. <= 63% rise over 48 hours
  • hCG level <= 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04341545


Contacts
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Contact: Man Wa Lui, MBBS 22553400 lmw632@ha.org.hk

Locations
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Hong Kong
Department of Obstetrics and Gynaecology, Queen Mary Hospital
Hong Kong, Hong Kong
Sponsors and Collaborators
Queen Mary Hospital, Hong Kong
Investigators
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Study Director: Ernest H.Y. Ng, MD The University of Hong Kong
Publications:
Elson CJ SR, Potdar N, Chetty M, Ross JA, Kirk EJ on behalf of the Royal College of Obstetricians and Gynaecologists. Diagnosis and Management of Ectopic Pregnancy. BJOG: An International Journal of Obstetrics & Gynaecology. 2016;123(13):e15-e55.
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.

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Responsible Party: Lui Man Wa, Associate consultant, Queen Mary Hospital, Hong Kong
ClinicalTrials.gov Identifier: NCT04341545    
Other Study ID Numbers: UW 20-005
First Posted: April 10, 2020    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Other researchers may contact the chief investigator for the request of individual participant data.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Lui Man Wa, Queen Mary Hospital, Hong Kong:
Tubal ectopic pregnancy
Methotrexate
Letrozole
Additional relevant MeSH terms:
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Pregnancy, Ectopic
Pregnancy, Tubal
Cardiac Complexes, Premature
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Pathologic Processes
Pregnancy Complications
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs