Letrozole + Misoprostol for Miscarriage

(LeMi Trial)

Overseen By Arden McAllister, MPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Disqualifiers: Incomplete abortion, Allergy to letrozole, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

30 Participants Needed

Trial Summary

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}

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.

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.

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

Treatment Details

Interventions

• Letrozole
• Misoprostol

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

In a study of 438 women, the addition of letrozole to misoprostol significantly improved the success rate of complete miscarriage and reduced the time from treatment to expulsion compared to placebo (p < 0.001).

While letrozole enhanced efficacy, it was associated with a higher incidence of nausea and vomiting, indicating a trade-off between improved outcomes and increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole vs. Placebo Pretreatment in the Medical Management of First Trimester Missed Miscarriage: a Randomized Controlled Trial. Torky, HA., Marie, H., ElDesouky, E., et al.[2022]

This study is a randomized controlled trial involving 294 women with first-trimester missed miscarriage, comparing the effectiveness of letrozole and mifepristone pretreatment followed by misoprostol in achieving complete abortion rates.

The trial aims to determine if letrozole is non-inferior to mifepristone in terms of complete abortion rates, potentially offering a less invasive medical treatment option for missed miscarriage.

NCBI (Pubmed)

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. Du, L., Li, RHW., Gemzell-Danielsson, K., et al.[2022]

Letrozole pre-treatment is shown to be non-inferior to mifepristone pre-treatment for complete evacuation in the medical treatment of first-trimester missed miscarriage, with complete evacuation rates of 97.8% for letrozole and 97.2% for mifepristone among 294 women studied.

Women in the letrozole group experienced less heavy post-treatment bleeding and returned to menses earlier, indicating potential benefits in terms of safety and recovery, while overall satisfaction rates were high in both treatment groups.

NCBI (Pubmed)

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. Du, L., Li, HWR., Gemzell-Danielsson, K., et al.[2023]

In a study involving 120 women with missed abortion, the addition of letrozole to a misoprostol regimen did not significantly increase the rate of complete abortion compared to misoprostol alone, with 80% success in the letrozole group versus 75% in the control group (P=0.80).

The mean time to complete abortion was similar between the two groups, indicating that misoprostol alone is as effective as the combination treatment for managing first-trimester missed abortions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of misoprostol with and without letrozole on the induction of abortion for women with first-trimester missed abortion. Allameh, Z., Goharian, M., Eslamian, M.[2020]

In a study of 168 women seeking medical termination of early pregnancy, the combination of letrozole and misoprostol resulted in a significantly higher complete abortion rate (86.9%) compared to misoprostol alone (72.6%).

The letrozole group also experienced fewer side effects, with only 8.3% reporting vomiting compared to 19.0% in the placebo group, indicating a better tolerability profile for the combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. Lee, VCY., Ng, EHY., Yeung, WSB., et al.[2022]

In a study of 128 women undergoing first-trimester abortion for non-viable pregnancies, the combination of letrozole and misoprostol resulted in a significantly higher complete abortion rate of 93.7% compared to 68.7% with misoprostol alone.

The intervention group experienced lower abdominal pain and shorter bleeding duration, indicating that letrozole pretreatment not only enhances efficacy but also improves the overall experience of the procedure without increasing side effects.

NCBI (Pubmed)

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. Abbasalizadeh, F., Sahhaf, F., Sadeghi-Shabestari, P., et al.[2020]

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]

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]

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]

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]

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

Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. [2022]

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]