Multimodal Uterotonics at the Time of Cesarean Section in Laboring Patients

NCT ID: NCT03904446

Last Updated: 2022-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-08
• Study Completion Date: 2021-02-15

Brief Summary

Postpartum hemorrhage remains a leading cause of maternal morbidity and mortality worldwide, even in high income countries. Uterine atony is estimated to cause 70-80% of postpartum hemorrhage. Prolonged labor and augmented labor are known risk factors for postpartum hemorrhage. In attempts to reduce the incidence of postpartum hemorrhage, particularly in patients with known risks factors, it is essential to optimize preventative practices in order to reduce the rates postpartum hemorrhage.

Although oxytocin is considered the first line therapy for preventing and treating uterine atony, early consideration of additional prophylactic uterotonic agents may be indicated in women with prior oxytocin exposure given oxytocin receptor desensitization and down regulation.

As such, investigators sought to examine whether multimodal prophylactic uterotonics (standard oxytocin + methylergonovine), in patients who are increased risk of developing postpartum hemorrhage (specifically laboring patients who ultimately require a cesarean section) would benefit from the addition of prophylactic uterotonics. The clinical rational for administration of multimodal prophylactic uterotonics at the time of cesarean delivery in laboring patients is three-fold: to decrease the incidence of uterine atony, to decrease the incidence of postpartum hemorrhage, decrease the number of uterotonics required at the time of cesarean section.

The primary outcome will be to evaluate the need for additional uterotonic agents (Methylergonovine, Carboprost, Misoprostol) at the time of delivery.

Secondary outcomes will include the incidence of postpartum hemorrhage (quantitative blood loss >1 liter), surgical assessment of uterine tone four minutes following delivery of the placenta, preoperative and postoperative hemoglobin, the need for a blood transfusion, intensive care unit admission, uterine infection (endometritis).

Detailed Description

All patients who meet eligibility for the study will be consented during their clinic visit or upon arrival to labor and delivery. If patients elect to participate in the study, enrollment in the study will be noted in their sticky note in EPIC (electronic medical record) which will be ready available to all members of the health care team. If patients during the labor process require a cesarean section, the anesthesiologist will pick up a sealed envelope (which will contain the allocation sequence and group assignment). A randomization block design with mixed block sizes will be used to generate the allocation sequence by using the nQuery Advisor computer software.

The sealed envelopes will be readily available to the anesthesiologist and kept in the anesthesia workroom. Following delivery of the infant, the patient will receive the standard oxytocin infusion. Following administration of the oxytocin infusion, the patient will be given either methylergonovine 0.2 mg IM (intramuscular) or placebo (1 ml of normal saline, intramuscular). This will be drawn up and administered by the anesthesiologist. The obstetrician (delivering provider performing the cesarean section) will be blinded to the group assignment. Documentation of the drug will be recorded in epic in the medication administration record.

The delivering provider will be responsible for determining and relaying to the anesthesiologist whether additional uterotonics are needed throughout the procedure. Additional uterotonics will be given in accordance to the current guidelines outlined by the American Congress of Obstetricians and Gynecologists (ACOG). The delivery provider will assess uterine tone at 4 minutes (satisfactory versus unsatisfactory). The registered nurse will be responsible for setting up a timer to let the OB provider know when 4 minutes have passed. Nursing will call out once the 4 minutes have passed and the OB provider will state whether adequate tone was noted. The anesthesiologist will be responsible for documenting whether a placebo/study drug was given and uterine tone after 4 minutes. This documentation will be placed back into the sealed envelope by the anesthesiologist and placed in the anesthesia workroom. Nicole Masse (primary investigator) will be responsible for storing folders in a secured, locked file cabinet within the Maternal Fetal Medicine offices.

As routinely done at the time of cesarean delivery, the registered nurse will be responsible for measuring and documenting the quantitative blood loss. As routinely performed on all are patients who undergo a vaginal or cesarean delivery, preoperative hemoglobin and postoperative day one hemoglobin levels will be collected.

In the event a postpartum hemorrhage was to occur, the obstetrician will then be un-blinded as management of a postpartum hemorrhage will be driven by whether normal saline or methergine was given as part of the study.

The primary outcome, the need for additional uterotonics, will be assessed in the operating room. Other outcome which will be assessed in the operating room include uterine tone and quantitative blood loss. Outcomes which will be assessed in the immediate postpartum period include: postpartum hemoglobin values, need for a blood transfusion, admission to the intensive care unit, endometritis).

No long-term follow will be needed.

Conditions

Uterine Atony With Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Methylergonovine 0.2 mg

Standard Oxytocin Infusion at the time of Cesarean Section plus 0.2 mg of Intramuscular Methergine

Group Type: EXPERIMENTAL

Methylergonovine

Intervention Type: DRUG

0.2 mg of intramuscular methylergonovine at the time of cesarean section following standard IV oxytocin infusion.

Placebo (Normal Saline)

Standard Oxytocin Infusion at the time of Cesarean Section plus 1 milliliter (mL)of normal saline given intramuscular

Group Type: PLACEBO_COMPARATOR

Normal Saline (placebo)

Intervention Type: DRUG

1 ml of normal saline intramuscular at the time of cesarean section following standard IV oxytocin infusion

Interventions

Methylergonovine

0.2 mg of intramuscular methylergonovine at the time of cesarean section following standard IV oxytocin infusion.

Intervention Type: DRUG

Normal Saline (placebo)

1 ml of normal saline intramuscular at the time of cesarean section following standard IV oxytocin infusion

Intervention Type: DRUG

Other Intervention Names

Methergine; Saline

Eligibility Criteria

Inclusion Criteria

• 18 years of age
• Laboring patients who undergo a cesarean section

Exclusion Criteria

• Placenta/Uterine Abnormalities
• Chronic Hypertension, Gestational Hypertension, Preeclampsia
• HIV/AIDS on protease inhibitors
• History of Coronary Artery Disease
• History of Hypersensitivity to Methylergonovine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Cynthia Wong

OTHER

Sponsor Role: lead

Responsible Party

Cynthia Wong

Physician-Professor-DEO

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nicole M Masse, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

References

Senturk S, Kagitci M, Balik G, Arslan H, Kir Sahin F. The Effect of the Combined Use of Methylergonovine and Oxytocin during Caesarean Section in the Prevention of Post-partum Haemorrhage. Basic Clin Pharmacol Toxicol. 2016 May;118(5):338-43. doi: 10.1111/bcpt.12500. Epub 2015 Nov 15.

Reference Type: BACKGROUND

PMID: 26449959 (View on PubMed)

Lavoie A, McCarthy RJ, Wong CA. The ED90 of prophylactic oxytocin infusion after delivery of the placenta during cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study. Anesth Analg. 2015 Jul;121(1):159-164. doi: 10.1213/ANE.0000000000000781.

Reference Type: BACKGROUND

PMID: 25902327 (View on PubMed)

Masse N, Dexter F, Wong CA. Prophylactic Methylergonovine and Oxytocin Compared With Oxytocin Alone in Patients Undergoing Intrapartum Cesarean Birth: A Randomized Controlled Trial. Obstet Gynecol. 2022 Aug 1;140(2):181-186. doi: 10.1097/AOG.0000000000004857. Epub 2022 Jul 6.

Reference Type: DERIVED

PMID: 35852267 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

201904756

Identifier Type: -

Identifier Source: org_study_id