Uterine Atony With HemorrhagePhase 4NCT03904446
Multimodal Uterotonics at the Time of Cesarean Section in Laboring Patients
A Phase 4 study testing Methylergonovine in people with Uterine Atony With Hemorrhage, run by Cynthia Wong at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Uterine Atony With Hemorrhage
- What is being tested?
- Methylergonovine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2019to 15 Feb 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18 years of age
- Laboring patients who undergo a cesarean section
Who cannot join
- Placenta/Uterine Abnormalities
- Chronic Hypertension, Gestational Hypertension, Preeclampsia
- HIV/AIDS on protease inhibitors
- History of Coronary Artery Disease
- History of Hypersensitivity to Methylergonovine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial to Assess the Effectiveness of Multimodal Prophylactic Uterotonics in Patients Undergoing Non-Elective Cesarean Sections After a Trial of Labor
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.
Read more
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).
Read the 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
- Being tested
- Methylergonovine, Normal Saline (placebo)
- Keywords
- Methergine, Uterine Atony
- Medical subject headings
- Uterine Inertia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylergonovineDrug
Also called Methergine
0.2 mg of intramuscular methylergonovine at the time of cesarean section following standard IV oxytocin infusion.
Normal Saline (placebo)Drug
Also called Saline
1 ml of normal saline intramuscular at the time of cesarean section following standard IV oxytocin infusion
| Study group | Role | What they receive |
|---|---|---|
| Methylergonovine 0.2 mg | Experimental | Standard Oxytocin Infusion at the time of Cesarean Section plus 0.2 mg of Intramuscular Methergine Receives: Drug: Methylergonovine |
| Placebo (Normal Saline) | Placebo comparator | Standard Oxytocin Infusion at the time of Cesarean Section plus 1 milliliter (mL)of normal saline given intramuscular Receives: Drug: Normal Saline (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Need for Additional Uterotonics (Methylergonovine, Carboprost, Misoprostol)
Categorical Variable (Yes/No) - Depending on whether patients required additional uterotonic agents the outcome measure will be yes or no.
Measured: Assessed from the time of cesarean section until 24 hours postdelivery
Secondary outcomes (4)
Quantitative Blood Loss
As per protocol, nurses will measure the quantitative blood loss by measuring the blood in the canisters used during the cesarean section and by weighing the sponges used in the surgery.
Measured: Quantitative Blood Loss is measured at the completion of the cesarean delivery, an average of 2 hours
The Difference Between the Preoperative and Postoperative (Postpartum Day 1) Hemoglobin Values
As per standard protocol, preoperative and postoperative day one hemoglobin levels will be evaluated. the difference between the preoperative and postoperative day 1 hemoglobin values will be calculated.
Measured: Preoperative hemoglobin level is collected on arrival to labor and delivery prior to the cesarean section, postoperative hemoglobin is collected on postoperative day one.
Number of Patients With Unsatisfactory Uterine Tone 4 Min Following Delivery as Assessed by the Obstetrician
Nursing will notify the obstetrical provider 4 minutes following delivery of the infant and the obstetrical provider will determine whether the uterine tone is noted to be satisfactory (uterus is contracted) or unsatisfactory (uterus boggy)
Measured: Obstetricians will assess the uterine tone 4 minutes following delivery of the infant
The Number of Patients Who Required a Blood Transfusion During the Delivery Hospitalization
The number of patients who required a blood transfusion
Measured: The need for a blood transfusion during the cesarean section up until hospital discharge (which is typically postpartum day number 3 for patients undergoing cesarean delivery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study start8 Jun 2019
- Primary completion15 Feb 2021
- Study completion15 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Uterine Atony With HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cynthia Wong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Cynthia Wong, University of Iowa
- Investigators
- Nicole M Masse, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03904446
- Sponsor's protocol ID
- 201904756
- Status last verified
- Jul 2022
- First submitted
- 3 Apr 2019
- Last updated
- 1 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26449959Lavoie 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.
PubMed 25902327Masse 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.
PubMed 35852267
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial to Assess the Effectiveness of Multimodal Prophylactic Uterotonics in Patients Undergoing Non-Elective Cesarean Sections After a Trial of Labor
- ClinicalTrials.gov ID
- NCT03904446
- Acronym / sponsor ID
- 201904756
- Conditions
- Uterine Atony With Hemorrhage
- Keywords
- Methergine, Uterine Atony
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Cynthia WongUniversity, hospital or other
- Study start
- 8 Jun 2019 (actual)
- Primary completion
- 15 Feb 2021 (actual)
- Study completion
- 15 Feb 2021 (actual)
- First posted
- 5 Apr 2019 (actual)
- Results
- Posted 27 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylergonovine 0.2 mg | Experimental | Drug: MethylergonovineStandard Oxytocin Infusion at the time of Cesarean Section plus 0.2 mg of Intramuscular Methergine |
| Placebo (Normal Saline) | Placebo comparator | Drug: Normal Saline (placebo)Standard Oxytocin Infusion at the time of Cesarean Section plus 1 milliliter (mL)of normal saline given intramuscular |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 18 years of age
- Laboring patients who undergo a cesarean section
Key exclusion criteria (5 listed)
- Placenta/Uterine Abnormalities
- Chronic Hypertension, Gestational Hypertension, Preeclampsia
- HIV/AIDS on protease inhibitors
- History of Coronary Artery Disease
- History of Hypersensitivity to Methylergonovine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylergonovineAlso: Methergine0.2 mg of intramuscular methylergonovine at the time of cesarean section following standard IV oxytocin infusion. | Drug | Methylergonovine 0.2 mg |
| Normal Saline (placebo)Also: Saline1 ml of normal saline intramuscular at the time of cesarean section following standard IV oxytocin infusion | Drug | Placebo (Normal Saline) |
Primary outcome
Number of Participants With Need for Additional Uterotonics (Methylergonovine, Carboprost, Misoprostol)
Time frame: Assessed from the time of cesarean section until 24 hours postdelivery
Categorical Variable (Yes/No) - Depending on whether patients required additional uterotonic agents the outcome measure will be yes or no.
4 secondary outcomes
Quantitative Blood Loss
Time frame: Quantitative Blood Loss is measured at the completion of the cesarean delivery, an average of 2 hours
The Difference Between the Preoperative and Postoperative (Postpartum Day 1) Hemoglobin Values
Time frame: Preoperative hemoglobin level is collected on arrival to labor and delivery prior to the cesarean section, postoperative hemoglobin is collected on postoperative day one.
Number of Patients With Unsatisfactory Uterine Tone 4 Min Following Delivery as Assessed by the Obstetrician
Time frame: Obstetricians will assess the uterine tone 4 minutes following delivery of the infant
The Number of Patients Who Required a Blood Transfusion During the Delivery Hospitalization
Time frame: The need for a blood transfusion during the cesarean section up until hospital discharge (which is typically postpartum day number 3 for patients undergoing cesarean delivery)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26449959Senturk 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.
- Background: PubMed 25902327Lavoie 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.
- Derived from this study: PubMed 35852267Masse 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicole M Masse, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylergonovine in people with Uterine Atony With Hemorrhage, run by Cynthia Wong at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Need for Additional Uterotonics (Methylergonovine, Carboprost, Misoprostol) (time frame: Assessed from the time of cesarean section until 24 hours postdelivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03904446, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2022.