Indomethacin vs Ibuprofen for Preterm Labor

(TOCO Trial)

Overseen By Pamela Simmons, DO

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Woman's

Must not be taking: Ibuprofen, Indomethacin

Disqualifiers: Fetal anomaly, Prior cerclage, others

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

Compensation: Varies

Number of Visits: 1

Duration: 24 hours

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is comparing ibuprofen and indomethacin to see which one is better at helping pregnant women with cervical insufficiency keep their pregnancy longer when a stitch is placed in the cervix. Indomethacin and ibuprofen are both used to help prevent early labor, but ibuprofen has fewer side effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken ibuprofen or indomethacin in the 7 days before joining the study.

What data supports the effectiveness of the drug indomethacin for preterm labor?

Research shows that indomethacin is effective in delaying preterm labor, similar to other drugs like sulindac, and can help postpone delivery for up to 7 days, allowing time for necessary medical interventions. ^{1 2 3 4 5}

Is indomethacin safe for use in preterm labor?

Indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause fetal side effects such as constriction of the ductus arteriosus (a vital fetal blood vessel) and potential kidney function impairment. These side effects raise concerns about its safety for use in preterm labor. ^{6 7 8 9 10}

How does the drug indomethacin differ from other treatments for preterm labor?

Indomethacin is unique in its ability to delay preterm labor by inhibiting prostaglandin synthesis, which reduces uterine contractions. It is often compared to other drugs like nifedipine and sulindac, and while it is effective, it may have more fetal side effects compared to sulindac. ^{1 2 5 7 11}

Research Team

Pamela Simmons, DO

Principal Investigator

Woman's Hospital, Louisiana

Eligibility Criteria

This trial is for pregnant women between 16 and nearly 24 weeks along, with a single baby and intact membranes needing emergency cerclage to prevent early labor. They must be over 18, planning to deliver at Woman's Hospital, and not have used ibuprofen or indomethacin recently.

Inclusion Criteria

Intact membranes at time of enrollment

You are pregnant with only one baby and it is healthy.

I am 18 years old or older.

Exclusion Criteria

You have a significant birth defect in your baby.

Temperature greater than 100.4

I have had a stitch placed in my cervix to prevent early labor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either ibuprofen or indomethacin as perioperative prophylactic treatment following emergent cerclage placement

24 hours

1 visit (in-person)

Follow-up

Participants are monitored for gestational latency and preterm birth until delivery

Up to 26 weeks

Treatment Details

Interventions

• Ibuprofen
• Indomethacin

Trial Overview The study compares two drugs—ibuprofen (2400mg) and indomethacin (150mg)—to see which one better prolongs pregnancy after an emergency stitch (cerclage) is placed in the cervix due to premature dilation.

Participant Groups

Group I: Ibuprofen Active Control 1 Intervention

Ibuprofen 600 mg q6 hours for 24 hours- total dose of 2400mg- after emergent cerclage placement

Group II: Indomethacin Active Control 1 Intervention

Indomethacin 50 mg q8 hours for 24 hours- total dose of 150mg- after emergent cerclage placement

Ibuprofen is already approved in United States, Canada, European Union, Japan, China, Switzerland for the following indications:

Approved in United States as Advil for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Canada as Motrin for:

• Pain relief
• Fever reduction
• Inflammation

Approved in European Union as Nurofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Japan as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in China as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Switzerland as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Who Is Running the Clinical Trial?

Woman's

Lead Sponsor

Trials

18

Recruited

1,400+

References

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

Comparison of the efficacy and adverse effects of nifedipine and indomethacin for the treatment of preterm labor. [2016]

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

Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study. [2019]

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

The effectiveness of nifedipine/indomethacin combination therapy and nifedipine monotherapy for postponing preterm birth (25-34 weeks of gestation) in Sudanese women: a randomized clinical trial study protocol. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Prenatal use of indomethacin for preterm labor and renal function among very low birth weight infants. [2023]

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

Randomized comparative trial of indomethacin and sulindac for the treatment of refractory preterm labor. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of effects of cyclooxygenase inhibitors on myometrial contraction and constriction of ductus arteriosus in rats. [2019]

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

The antagonism by anti-inflammatory analgesics of prostaglandin f 2 alpha-induced contractions of human and rabbit myometrium in vitro. [2019]

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

OBE022, an Oral and Selective Prostaglandin F2α Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor. [2019]

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

Developmental toxicity evaluation of ibuprofen and tolmetin administered in triple daily doses to Wistar CRL:(WI)WUBR rats. [2013]

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

A prospective randomized safety trial of celecoxib for treatment of preterm labor. [2019]

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

The effects of a number of non-steroidal anti-inflammatory compounds on parturition in the rat. [2019]