Letrozole + Misoprostol for Miscarriage

(LeMi Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Pennsylvania

Disqualifiers: Incomplete abortion, Allergy to letrozole, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

A pilot cohort study to preliminarily investigate the efficacy of pretreatment with letrozole 10 mg daily for three consecutive days followed by treatment with misoprostol 800 mcg vaginally for medical management of early pregnancy loss in a US population. Patients will be followed to assess efficacy of this treatment regimen, as well as additional interventions needed, side effects, adverse events, and patient acceptability.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug combination of Letrozole and Misoprostol for miscarriage?

Research suggests that adding letrozole to misoprostol can increase the success rate of complete abortion in early pregnancy compared to using misoprostol alone. Letrozole is thought to enhance the effectiveness of misoprostol by preparing the body for the treatment.

^{1 2 3 4 5}

How is the drug combination of Letrozole and Misoprostol unique for treating miscarriage?

The combination of Letrozole and Misoprostol is unique because Letrozole, which has an anti-estrogen effect, is used as a pretreatment to enhance the effectiveness of Misoprostol, leading to a higher complete abortion rate and fewer side effects like abdominal pain and bleeding compared to using Misoprostol alone.

^{1 2 3 5 6}

Eligibility Criteria

This trial is for English-speaking adults over 18 who have had an early pregnancy loss, as confirmed by ultrasound. Participants must be willing to follow the study's procedures, have a working mobile phone, and can sign a consent form. It's not for those with incomplete abortion, allergies to the drugs being tested, unable to return for follow-up, or having multiple pregnancies.

Inclusion Criteria

Confirmed diagnosis of intrauterine embryonic/fetal demise or anembryonic gestation (ultrasound examination demonstrates a fetal pole without cardiac activity measuring between 5.3 and 40 mm or an abnormal growth pattern diagnostic of early pregnancy failure)

I am willing and able to follow the study rules and attend all required visits.

I have a working mobile phone.

Exclusion Criteria

Incomplete or inevitable abortion

I am not allergic to letrozole or misoprostol.

I cannot come back to the clinic for follow-up visits.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Pretreatment

Participants receive letrozole 10 mg orally daily for three consecutive days

3 days

Treatment

Participants receive misoprostol 800 mcg vaginally within 24 hours of final letrozole dose

1 day

Follow-up

Participants are monitored for efficacy, additional interventions, side effects, adverse events, and patient acceptability

30 days

Participant Groups

The study tests if taking letrozole (10 mg daily) for three days before using misoprostol (800 mcg vaginally) helps manage early pregnancy loss. Researchers will check how well this works and note any additional treatments needed, side effects or adverse events.

Group I: Letrozole & Misprostol Experimental Treatment 2 Interventions

Letrozole 10 mg orally daily for three consecutive days followed by misoprostol 800 mcg vaginally within 24 hours of final letrozole dose

Letrozole is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

🇪🇺 Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

🇨🇦 Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

PEACE / Penn Medicine Philadelphia, PA

Who Is Running the Clinical Trial?

University of Pennsylvania Lead Sponsor

References

1. Germany pubmed.ncbi.nlm.nih.gov

Letrozole vs. Placebo Pretreatment in the Medical Management of First Trimester Missed Miscarriage: a Randomized Controlled Trial. [2022] Misoprostol is used for the medical management of miscarriage as it is more effective in the early stages of pregnancy. Letrozole has an anti-estrogen effect and is used for the pretreatment of miscarriage with misoprostol.

2. England pubmed.ncbi.nlm.nih.gov

Prospective open-label non-inferiority randomised controlled trial comparing letrozole and mifepristone pretreatment in medical management of first trimester missed miscarriage: study protocol. [2022] Medical treatment is a less invasive alternative to surgical management of missed miscarriage. Studies have shown that pretreatment with mifepristone can increase the complete abortion rate in management of first-trimester missed miscarriage compared with misoprostol alone. Two studies have also shown that pretreatment with letrozole could increase the efficacy compared with misoprostol alone. So far, there is no trial comparing letrozole and mifepristone pretreatment for missed miscarriage. We designed this randomised controlled trial to test the hypothesis that for first-trimester missed miscarriage, letrozole pretreatment is non-inferior to mifepristone pretreatment followed by misoprostol in terms of complete abortion rate.

3. England pubmed.ncbi.nlm.nih.gov

Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial. [2023] To investigate whether letrozole pre-treatment is non-inferior to mifepristone pre-treatment, followed by misoprostol, for complete evacuation in the medical treatment of first-trimester missed miscarriage.

4. United States pubmed.ncbi.nlm.nih.gov

Effect of misoprostol with and without letrozole on the induction of abortion for women with first-trimester missed abortion. [2020] To determine whether addition of letrozole to a misoprostol-based abortion regimen can increase the rate of complete abortion.

5. United States pubmed.ncbi.nlm.nih.gov

Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. [2022] To compare the success rate and side effects of letrozole and misoprostol versus misoprostol alone for medical termination of early pregnancy.

6. Iran pubmed.ncbi.nlm.nih.gov

Comparison Between Effect of Letrozole Plus Misoprostol and Misoprostol Alone in Terminating Non-Viable First Trimester Pregnancies: A Single Blind Randomized Trial. [2020] Objective: To evaluate the effect of letrozole plus misoprostol to terminate non-viable pregnancies in first trimester compared with the use of misoprostol alone. Materials and methods: In a single-blind clinical trial, 128 women over 18 years old referred to Educational-Medical centers of Tabriz University of Medical Science (Tabriz, Iran), for abortion in first trimester of non-viable pregnancies, were randomly selected in two intervention and control groups using Rand list (version 1.2) software. To complete abortion both groups received 600 mcg of misoprostolorally. The intervention group received letrozole 10 mg daily for 3 days before receiving misoprostolorally. Complete abortion rate and the side effects of both groups were recorded. Results: Mean pregnancy age based on LMP in intervention group and control group were 7.74 ± 0.95 and 8.52 ± 1.29 weeks respectively. Complete abortion rate in the intervention group was 93.7%, and in control group was 68.7% which was significantly higher in intervention group (p = 0.001). Abdominal pain in the intervention group is also significantly lower than that of the control group (p = 0.013). Intervention group also had significantly lower duration of bleeding rather than control group (p = 0.006). Conclusion: Based on the findings of this study, letrozole pretreatment with misoprostol for first-trimester medical abortion can increase complete abortion rate significantly without increasing side effects compared to use of misoprostol alone.