Uterine AtonyEarly Phase 1NCT03303235
Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections
A Early Phase 1 study testing Methylergonovine in people with Uterine Atony and Uterine Tone Disorders, run by Johns Hopkins University at 1 site in United States.
Trial summary
Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Uterine Atony, Uterine Tone Disorders, Postpartum Hemorrhage
- What is being tested?
- Methylergonovine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2020to Dec 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- All patients admitted for elective cesarean section
- All laboring patients for planned vaginal delivery as these women may have an unplanned cesarean delivery for maternal or for fetal indications
- Patients not in labor but admitted for non-elective cesarean section
- Administration of oxytocin prior to administration of methylergonovine, in accordance to the ACOG guideline for postpartum hemorrhage
- Obstetrician's request for methylergonovine intraoperatively to the anesthesiologist
Who cannot join
- Fetus not considered to be of viable gestational age by obstetrical team
- Patients with hypertension (either chronic or pregnancy-induced, including preeclampsia)
- Patients with coronary artery disease, established and diagnosed by medical internist or cardiologist
- Patients taking CYP3A4 inhibitors
- Patients taking beta blockers.
- Patients with contraindications to any of the uterotonic agents for whatever medical reason (allergies, for example)
Show all 9Show fewer
- Surgeon request for administration of methylergonovine earlier than per protocol due to clinical situation as abovementioned
- Maternal or obstetrician refusal
- Patients who require obstetrical intervention before 30 minutes has elapsed
Trial locations and contacts
1 site in 1 country.
About this study
Official title: How's the Tone? Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections
Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin.
Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.
Read the detailed description
The United States is one of the few modern countries in which maternal peripartum mortality continues to rise. One of the three most important causes of maternal mortality is severe hemorrhage. Controlling postpartum uterine tone remains an important role for the obstetric anesthesiologist. Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin.
Methylergonovine maleate is a semi-synthetic ergot alkaloid. Methylergonovine(200 mcg) is administered intramuscularly when oxytocin has been administered but has not contracted the uterus sufficiently. It is not without side effects, however. Due to its vasoconstrictive properties, methylergonovine has been shown to elevate blood pressures and is avoided in preeclamptic patients who may not tolerate abrupt increases in blood pressures. Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.
- Conditions
- Uterine Atony, Uterine Tone Disorders, Postpartum Hemorrhage
- Being tested
- Methylergonovine
- Keywords
- methylergonovine
- Medical subject headings
- Uterine Inertia, Postpartum Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylergonovineDrug
Also called methergine
IV vs IM
| Study group | Role | What they receive |
|---|---|---|
| IV Methergine | Experimental | IV methylergonovine group
-IM 0.9% NaCl (1 ml)) + IV methylergonovine (2 mcg/ml) infusion (100 ml) Receives: Drug: Methylergonovine |
| Conventional | Active comparator | IM methylergonovine group
-200 mcg IM methylergonovine (1 ml) + IV 0.9% NaCl infusion (100 ml) Receives: Drug: Methylergonovine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to achieve "adequate" uterine tone
Our primary objective is to determine the time to achieve "adequate" uterine tone with either intramuscular (IM) dose versus intravenous (IV) dose methylergonovine, when oxytocin has failed to do so in cesarean sections.
Measured: 10 minutes
Secondary outcomes (6)
Dose that achieves "adequate" uterine tone
Determining dose that achieves "adequate" uterine tone as defined by obstetricians on a qualitative numerical scale defined prior to the study (0 to 10 with 0 being inability of uterus to contract (i.e. uterine atony) to 10 being fully contracting uterus; "adequate" would be >5 on the scale)
Measured: 3 minutes
Need for additional uterotonic agents
Quantifying need for additional uterotonic agents as outlined by the postpartum hemorrhage guidelines set forth by ACOG
Measured: 3 minutes
Frequency of side effects of methylergonovine
Determining frequency of side effects of methylergonovine, including blood pressure changes, especially if elevated >20% preoperative level), headache, nausea, and vomiting
Measured: 30 minutes
Need for vasopressors
To determine if the patient requires a vasopressor (including phenylephrine, ephedrine, epinephrine, norepinephrine or vasopressin)?
Measured: 3 minutes
Estimated blood loss
Utilizing estimated blood loss by suction canister + estimated weight of blood on surgical lap
Measured: 2 hours
Computed blood loss
Calculating changes in hematocrit (Hct preop - Hct postop)
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2017
- Study startJul 2020 (estimated)
- Primary completionOct 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: Collaborators left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uterine AtonyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Karen Lindeman, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03303235
- Sponsor's protocol ID
- IRB00120873
- Status last verified
- Jul 2020
- First submitted
- 26 Sep 2017
- Last updated
- 3 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- How's the Tone? Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections
- ClinicalTrials.gov ID
- NCT03303235
- Acronym / sponsor ID
- IRB00120873
- Conditions
- Uterine Atony, Uterine Tone Disorders, Postpartum Hemorrhage
- Keywords
- methylergonovine
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Collaborators left the institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jul 2020 (estimated)
- Primary completion
- Oct 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 5 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin.
Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.
Detailed description
The United States is one of the few modern countries in which maternal peripartum mortality continues to rise. One of the three most important causes of maternal mortality is severe hemorrhage. Controlling postpartum uterine tone remains an important role for the obstetric anesthesiologist. Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin.
Methylergonovine maleate is a semi-synthetic ergot alkaloid. Methylergonovine(200 mcg) is administered intramuscularly when oxytocin has been administered but has not contracted the uterus sufficiently. It is not without side effects, however. Due to its vasoconstrictive properties, methylergonovine has been shown to elevate blood pressures and is avoided in preeclamptic patients who may not tolerate abrupt increases in blood pressures. Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV Methergine | Experimental | Drug: MethylergonovineIV methylergonovine group -IM 0.9% NaCl (1 ml)) + IV methylergonovine (2 mcg/ml) infusion (100 ml) |
| Conventional | Active comparator | Drug: MethylergonovineIM methylergonovine group -200 mcg IM methylergonovine (1 ml) + IV 0.9% NaCl infusion (100 ml) |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- All patients admitted for elective cesarean section
- All laboring patients for planned vaginal delivery as these women may have an unplanned cesarean delivery for maternal or for fetal indications
- Patients not in labor but admitted for non-elective cesarean section
- Administration of oxytocin prior to administration of methylergonovine, in accordance to the ACOG guideline for postpartum hemorrhage
- Obstetrician's request for methylergonovine intraoperatively to the anesthesiologist
Key exclusion criteria (9 listed)
- Fetus not considered to be of viable gestational age by obstetrical team
- Patients with hypertension (either chronic or pregnancy-induced, including preeclampsia)
- Patients with coronary artery disease, established and diagnosed by medical internist or cardiologist
- Patients taking CYP3A4 inhibitors
- Patients taking beta blockers.
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: methergineIV vs IM | Drug | Conventional, IV Methergine |
Primary outcome
Time to achieve "adequate" uterine tone
Time frame: 10 minutes
Our primary objective is to determine the time to achieve "adequate" uterine tone with either intramuscular (IM) dose versus intravenous (IV) dose methylergonovine, when oxytocin has failed to do so in cesarean sections.
6 secondary outcomes
Dose that achieves "adequate" uterine tone
Time frame: 3 minutes
Need for additional uterotonic agents
Time frame: 3 minutes
Frequency of side effects of methylergonovine
Time frame: 30 minutes
Need for vasopressors
Time frame: 3 minutes
Estimated blood loss
Time frame: 2 hours
Computed blood loss
Time frame: 2 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Individual participant dataSharing planned: Undecided
Related trials for Uterine Atony
Not yet recruiting
Comparison of Effect of Two Different Doses of Intravenous Oxytocin on Patients Undergoing Elective Cesarean Section
Postpartum Hemorrhage, Uterine Atony
RecruitingPhase 4
Carbetocin Monotherapy Versus Carbetocin Plus Oxytocin Infusion in Elective Cesarean Delivery: A Non-Inferiority Trial
Postpartum Hemorrhage, Uterine Atony
Not yet recruitingPhase 4
Oxytocin Bolus Versus Infusion in High-Risk Patients Undergoing Elective Cesarean Section (INBOX-HR)
Postpartum Hemorrhage, Uterine Atony
RecruitingPhase 2
Prophylactic Intravenous Calcium Gluconate to Decrease Blood Loss at Time of Cesarean Delivery in Pregnant Patients at High Risk for Uterine Atony
Blood Loss, Surgical, Blood Loss, Postoperative
Recruiting
Administration Of Calcium Gluconate for The Reduction of Blood Loss During Vaginal Delivery
Postpartum Hemorrhage
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.
Karen Lindeman, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Methylergonovine in people with Uterine Atony and Uterine Tone Disorders, run by Johns Hopkins University 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 5 inclusion and 9 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: withdrawn, as of the sponsor's last update on 3 Aug 2020. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Time to achieve "adequate" uterine tone (time frame: 10 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Aug 2020.