Mifepristone + Misoprostol for Second Trimester Miscarriage

(MIST Trial)

Overseen By Katherine H Bligard, MD,MA

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Washington University School of Medicine

Disqualifiers: Contraindication to mifepristone, 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: 1

Duration: 24-48 hours

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug combination of Mifepristone and Misoprostol for second trimester miscarriage?

Research shows that using mifepristone before misoprostol is more effective than using misoprostol alone for second-trimester pregnancy termination, as it can lead to quicker delivery and fewer complications. This suggests that the combination may also be effective for managing second trimester miscarriages. ^{1 2 3 4 5}

Is the combination of Mifepristone and Misoprostol generally safe for use in humans?

The combination of Mifepristone and Misoprostol is generally considered safe for use in humans, with side effects like pelvic pain and malaise being rare. Serious complications are very uncommon, but careful medical monitoring is recommended after administration. ^{2 6 7 8 9}

How is the drug Mifepristone + Misoprostol unique for second trimester miscarriage?

The combination of Mifepristone and Misoprostol is unique because it effectively induces abortion in the second trimester with a short time to delivery and high success rate, without needing additional prostaglandin agents. This method is also flexible in administration routes, offering both oral and vaginal options. ^{2 10 11 12 13}

What is the purpose of this trial?

When time allows, administration of mifepristone prior to second trimester induction of labor decreases total labor time. However, in the setting of many pregnancy complications, decreasing time from diagnosis of nonviable pregnancy to delivery is of utmost importance to decrease risk of maternal complications. Previous data has shown that total abortion time is longer in the group receiving mifepristone owing to the delay between mifepristone administration and initiation of misoprostol induction of labor. Thus, the investigators aim to investigate whether simultaneous mifepristone and misoprostol has benefits over misoprostol alone when labor induction of a nonviable second trimester cannot be delayed.

Eligibility Criteria

This trial is for adults over 18 who are between 14 and 28 weeks pregnant with a single nonviable fetus, meaning the fetus has passed away or cannot survive due to its gestational age/weight or a fatal condition.

Inclusion Criteria

I am between 14 and 28 weeks pregnant.

You are pregnant with only one baby.

The baby in your womb is no longer alive or has a condition that makes survival impossible.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either misoprostol alone or simultaneous mifepristone and misoprostol for induction of labor

24-48 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after induction of labor

During admission

Treatment Details

Interventions

• Mifepristone
• Misoprostol

Trial Overview The study is testing if taking Mifepristone and Misoprostol at the same time offers any benefits compared to just Misoprostol alone in inducing labor when dealing with a nonviable second trimester pregnancy.

Participant Groups

Group I: Simulatenous mifepristone and misoprostol Experimental Treatment 2 Interventions

Participants will receive a dose of 200mg oral mifepristone at time of induction with misoprostol

Group II: Misoprostol alone Active Control 1 Intervention

Participants will have labor induced with misoprostol alone

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

Approved in United States as Mifeprex for:

• Abortion
• Cushing's Syndrome

Approved in European Union as Mifegyne for:

• Abortion
• Cushing's Syndrome

Approved in Canada as Mifeprex for:

• Abortion
• Cushing's Syndrome

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

Pretreatment with mifepristone significantly increases the likelihood of complete uterine evacuation within 15 hours compared to misoprostol alone, with a relative risk of 2.16 (79.8% vs. 36.9%).

The time from induction to abortion is shorter for women who received mifepristone (8.1 hours) compared to those who only received misoprostol (10.6 hours), while both treatments have similar side-effect profiles and high acceptability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial. Ngoc, NTN., Shochet, T., Raghavan, S., et al.[2021]

In a study of 99 patients, the method of using mifepristone and misoprostol for pregnancy termination or intrauterine fetal death resulted in a high delivery rate within 24 hours (96% for fetal death and 92% for termination).

The median duration of treatment was longer for intrauterine fetal death (10 hours) compared to pregnancy termination (8 hours), but overall complication rates and side effects were consistent with previous studies, indicating the method's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of pregnancy termination for foetal congenital or chromosomal disorders or intrauterine foetal death by oral mifepristone and/or intravaginal misoprostol; results of a retrospective study]. Verhulsdonk, MT., Papatsonis, DN., Heydanus, R.[2013]

In a study of 270 women, vaginal administration of misoprostol after mifepristone resulted in a higher success rate for abortion without surgical intervention (95% vs. 87% for oral administration), indicating greater efficacy of the vaginal route.

Vaginal misoprostol also led to faster abortions, with 93% of women aborting within four hours compared to 78% with the oral route, and it had fewer side effects like vomiting and diarrhea, making it a better-tolerated option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. el-Refaey, H., Rajasekar, D., Abdalla, M., et al.[2013]

A combined regimen of mifepristone and misoprostol is significantly more effective than misoprostol alone for inducing complete expulsion in first trimester abortions, with a risk ratio of 1.19 based on a meta-analysis of 9 studies involving 2,052 participants.

This combined treatment not only reduces the likelihood of incomplete abortions and ongoing pregnancies but also shows a lower incidence of fever, although it may lead to increased subjective bleeding experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mifepristone plus misoprostol with misoprostol alone for first trimester medical abortion: A systematic review and meta-analysis. Shimels, T., Getnet, M., Shafie, M., et al.[2023]

In a study of 133 samples of early abortions induced by mifepristone (RU486) and misoprostol (Miso), no significant differences were found in outcomes or pathological changes between different dosages of the drugs.

The villi from the RU486-Miso group exhibited more severe degeneration compared to control samples from vacuum aspiration, suggesting a potential impact of RU486 on trophoblasts, although the exact mechanism remains unclear and requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The pathological investigations on termination of early pregnancy with mifepristone]. Liu, B., Sun, J., Tao, W.[2013]

RU486 (mifepristone) combined with a prostaglandin analogue has a high efficacy rate of 95.3% for early pregnancy termination, with a slight increase to 96.9% when followed by misoprostol, indicating it is a reliable medical alternative to surgical procedures.

While the treatment is generally safe, there are potential side effects and serious adverse events, including a fatality, which necessitate careful medical monitoring for several hours after administration of the prostaglandin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RU486: the French experience. Ulmann, A., Silvestre, L.[2019]

Combining mifepristone with misoprostol significantly shortens the induction-abortion interval in second-trimester abortions, as shown in a study of 60 patients, which helps reduce side effects and hospital stay duration.

The study supports the safety and efficacy of this combination treatment, making it a reliable and cost-effective option for elective abortions between 13 and 20 weeks of gestation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-induction with Mifepristone for Second Trimester Termination of Pregnancy. Kulkarni, KK.[2021]

In a study involving 35 patients, mifepristone (RU486) was safely administered for therapeutic interruption of pregnancy, with no recorded toxicity or maternal morbidity.

Mifepristone effectively modified cervical consistency, improving cervical calibration regardless of the dose used (150 mg or 450 mg), which may facilitate the labor process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone (RU486) and therapeutic late pregnancy termination: a double-blind study of two different doses. Frydman, R., Fernandez, H., Pons, JC., et al.[2019]

In a study of 62 patients undergoing medical termination of early pregnancy with mifepristone (RU 486) and a prostaglandin analogue, the method achieved a high success rate of 97%.

The procedure had rare side effects, although about half of the patients required strong analgesics, indicating that while effective, pain management is an important consideration during the process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Reintroduction of medical abortion in Denmark]. Olsen, CD., Wittendorff, HE., Jørgensen, JJ.[2014]

In a study of 70 women, the combination of mifepristone and misoprostol achieved a 97% success rate for inducing second trimester abortion, demonstrating high efficacy without the need for additional prostaglandin agents.

The average time from induction to abortion was 6.4 hours, and no significant differences were found between vaginal and combined vaginal/oral administration routes, suggesting flexibility in how misoprostol can be administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens. el-Refaey, H., Templeton, A.[2019]

In a study of 50 women undergoing second trimester pregnancy termination, misoprostol was found to be as effective as gemeprost when used with mifepristone, with no significant difference in the time it took for the abortion to occur (8.7 hours for misoprostol vs. 10.8 hours for gemeprost).

Both medications resulted in similar side effects, indicating that misoprostol is a safe alternative to gemeprost for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial. Ho, PC., Chan, YF., Lau, W.[2014]

Mifepristone combined with misoprostol (MM) has a lower failure rate for second-trimester abortion (2.0% to 5.9%) compared to ethacridine lactate (EL) (7.4% to 20.7%), indicating higher efficacy for MM.

The MM method also results in shorter labor and hospitalization times, although it is associated with more gastrointestinal side effects, while EL is linked to a higher incidence of cervical injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Termination of second-trimester pregnancy by mifepristone combined with misoprostol versus intra-amniotic injection of ethacridine lactate (Rivanol®): a systematic review of Chinese trials. Hou, SP., Fang, AH., Chen, QF., et al.[2018]

A case study of a 30-year-old woman who had a second-trimester abortion after a previous cesarean delivery revealed a rare but serious complication: vesicouterine rupture, where the fetus escaped into the bladder.

The case emphasizes the need for close monitoring of patients with prior cesarean sections during medical abortions, as early detection of complications can lead to successful conservative surgical management and preservation of fertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined vesicouterine rupture during second-trimester medical abortion for fetal abnormality after prior cesarean delivery: A case report. Caruso, G., Paladini, V., D'ambrosio, V., et al.[2022]

References

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

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Results of pregnancy termination for foetal congenital or chromosomal disorders or intrauterine foetal death by oral mifepristone and/or intravaginal misoprostol; results of a retrospective study]. [2013]

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

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of mifepristone plus misoprostol with misoprostol alone for first trimester medical abortion: A systematic review and meta-analysis. [2023]

5. China pubmed.ncbi.nlm.nih.gov

[The pathological investigations on termination of early pregnancy with mifepristone]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

RU486: the French experience. [2019]

7. India pubmed.ncbi.nlm.nih.gov

Pre-induction with Mifepristone for Second Trimester Termination of Pregnancy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Mifepristone (RU486) and therapeutic late pregnancy termination: a double-blind study of two different doses. [2019]

9. Denmark pubmed.ncbi.nlm.nih.gov

[Reintroduction of medical abortion in Denmark]. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens. [2019]

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

Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial. [2014]

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

Termination of second-trimester pregnancy by mifepristone combined with misoprostol versus intra-amniotic injection of ethacridine lactate (Rivanol®): a systematic review of Chinese trials. [2018]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Combined vesicouterine rupture during second-trimester medical abortion for fetal abnormality after prior cesarean delivery: A case report. [2022]