PreeclampsiaPhase 3VasopressorsNCT01451060
Maternal and Neonatal Outcomes of the Use of Vasopressors to Treat Hypotension During Spinal Anesthesia for Cesarean
A Phase 3 study testing Metaraminol and Ephedrine in people with Preeclampsia and Pregnancy Toxemias, run by Instituto Materno Infantil Prof. Fernando Figueira at 1 site in Brazil.
Trial summary
Anesthesia for cesarean section has been a great challenge for the anesthesiologist, for mother and fetus are closely related. So the challenge is to anesthetize the mother without interfering with the physiology of the fetus. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Preeclampsia, Pregnancy Toxemias
- What is being tested?
- Metaraminol and Ephedrine
- How many people
- 0 participants
- Where
- 1 siteBrazil
- Study dates
- Jun 2011to Jul 2014
- Phase
- Phase 3
- 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Severe preeclampsia with indication of cesarean section
- Informed consent for study participation
- Age above 34 weeks gestational
- Single Pregnancy
Who cannot join
- Hemorrhagic syndromes of pregnancy (placenta previa, DPPNI)
- Help Syndrome
- Eclampsia
- Cardiovascular or Cerebrovascular Disease
- Fetal distress Absolute contraindications to spinal anesthesia (coagulopathy, sepsis and hypovolemia)
- Pregnant unable to decide on participation in the study (unconscious, confused, coma, mental retardation)
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Instituto de Medicina Integral Professor Fernando Figueira
Recife, Pernambuco, 52050050
About this study
Official title: Maternal and Neonatal Outcomes After the Use of Vasopressors to Correct Hypotension During Cesarean Section Under Spinal Anesthesia in Pregnant Women With Severe Preeclampsia: Randomized Clinical Trial
Anesthesia for cesarean section has been a great challenge for the anesthesiologist, for mother and fetus are closely related. So the challenge is to anesthetize the mother without interfering with the physiology of the fetus. The spinal block, although safe, are not free of complications if not treated properly, may be responsible for increased fetal morbidity. Among the major side effects, there is hypotension, with potentially serious consequences for the maternal-fetal dyad. Hypotension in pregnant women at low risk may not lead to major damage, but a pregnant woman with low reserves, as is the case of pregnant women with pre-eclampsia, any drop in blood pressure of the mother can bring harm to the welfare of mother and fetus. Based on the above, the purpose of this study is to compare the effects of maternal and perinatal treatment of hypotension with ephedrine or metaraminol in pregnant women with severe preeclampsia undergoing cesarean section under spinal anesthesia. There will be a randomized, double-blind, which will be included pregnant women with severe preeclampsia with indication of cesarean section, gestational age above 34 weeks gestation and only.Will be Excluded women with hemorrhagic syndromes of pregnancy, HELLP syndrome, eclampsia, cardiovascular or cerebrovascular disease, fetal distress and absolute contraindications to spinal anesthesia.
All patients are fully informed of the research objectives and will only be included in the study if they agree to participate and sign the Instrument of Consent. The project was designed following the recommendations of Resolution 196/96 of the National Health and the Declaration of Helsinki for research involving human subjects (2000). In addition, the project was submitted to the Ethics Committee in Research of the Institute of Integrative Medicine Professor Fernando Figueira, is approved. The study will be conducted from June 2011 to July 2012. The study variables are: consumption of metaraminol and ephedrine before and after birth, the occurrence of nausea and vomiting, incidence of maternal hypotension, the occurrence of reactive hypertension, occurrence of bradycardia, pH of umbilical cord, Apgar score 5 minutes, need for face mask ventilation and ICU admission.
Read the detailed description
Ephedrine, a long time was considered the safest drug for both mother and fetus during the treatment of hypotension in Caesarean section. However, recent evidence shows that contrary to what was thought, ephedrine appears to increase fetal metabolism, decreasing the pH and excess base.
Recently, phenylephrine has been used in the treatment of hypotension during cesarean delivery with better results in relation to acid-base parameters in umbilical cord blood. However, few data are available on the use of phenylephrine in high-risk pregnancy, the majority of studies in healthy pregnant women for elective caesarean section.
Although little scientific evidence regarding the use of metaraminol for treatment of hypotension in Caesarean section, recent study demonstrated superiority of this drug compared to ephedrine, checking a lower incidence of neonatal acidosis and better control of blood pressure. The researchers also found differences in blood gases from the umbilical cord between the ephedrine and metaraminol groups larger than those already found in previous studies comparing ephedrine and phenylephrine.
The pathophysiological changes in patients with pre-eclampsia can lead to intrauterine growth restriction with chronic fetal distress, due to the limited uteroplacental flow, which, in certain situations, may be reduced by 50% to 70%. Added to this, spinal anesthesia may cause sudden hypotension and fetal acidosis more often, even in elective operations, compared to epidural or general anesthesia, and that these changes may not have clinical significance in healthy fetuses at term, but may be critical in situations where arterial insufficiency uteroplacental and fetal distress already to present. It is believed, therefore, important that treat or prevent hypotension in patients with severe preeclampsia under spinal anesthesia.
Prevention of hypotension in patients with severe preeclampsia does not require large amounts of intravenous fluids, but careful prophylaxis of postural hypotensive syndrome. Despite the care, if hypotension occurs, aggressive treatment is mandatory in these patients and fast in order to avoid worsening fetal distress and neonatal depression. Such patients are more sensitive to vasopressors, therefore, small doses should be administered.
However, the biggest challenge of the anesthesiologist is to determine the ideal vasopressor in pregnant women at high risk, able to adequately restore blood pressure levels without determining deterioration of fetal status.
30 Reynolds and Seed in 2005 showed that ephedrine, administered in large doses, has contributed to the adverse effects of spinal anesthesia (greater degree of fetal metabolic acidosis), supporting the idea that ephedrine is not the vasopressor of choice for treatment of maternal hypotension during cesarean section.
As a result, this study is to fill this knowledge gap, taking on great importance to evaluate maternal and perinatal outcomes of pregnant women with severe preeclampsia to receive ephedrine or metaraminol for treatment of maternal hypotension during caesarean section under spinal anesthesia. Considering the importance of creating a protocol, since the metaraminol, unlike phenylephrine, is widely available at our facility.
- Conditions
- Preeclampsia, Pregnancy Toxemias
- Being tested
- Metaraminol, Ephedrine
- Keywords
- vasopressors, cesarean anesthesia, hypotension
- Medical subject headings
- Pre-Eclampsia, Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetaraminolDrug
Also called Aramin
It will be used a dose of 0.5 mg to any fall in blood pressure of the fetus until birth
EphedrineDrug
Also called Ephedrin
It will be used at any one dose de1mg fall in blood pressure of the fetus until birth
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of maternal hypotension
Participants are accompanied throughout their cesarean section an average of 30 minutes, where they will be measured blood pressure and heart rate every three minutes until the end of cesarean section.
Measured: During the caesarean, on average during the first 30 minutes after spinal anesthesia
Secondary outcomes (1)
Maternal and Neonatal outcomes
After the birth of neonatal up to the high infant, an average of 30 days
Measured: During the cesarean section and postpartum until discharge (an average of 24 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2011 (estimated)
- Study startJun 2011
- Primary completionJun 2014 (estimated)
- Study completionJul 2014 (estimated)
Why it stopped: We didn't have enough financial support
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PreeclampsiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Materno Infantil Prof. Fernando Figueira
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flavia orange, Instituto Materno Infantil Prof. Fernando Figueira
- Investigators
- Antonio Monteiro, MD, Study director, Instituto de Medicina integral Professor Fernando Figueira
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451060
- Sponsor's protocol ID
- 2300-11
- Acronym
- Vasopressors
- Status last verified
- Oct 2011
- First submitted
- 1 Aug 2011
- Last updated
- 7 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: We don't have data to share
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal and Neonatal Outcomes After the Use of Vasopressors to Correct Hypotension During Cesarean Section Under Spinal Anesthesia in Pregnant Women With Severe Preeclampsia: Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT01451060
- Acronym / sponsor ID
- Vasopressors / 2300-11
- Conditions
- Preeclampsia, Pregnancy Toxemias
- Keywords
- vasopressors, cesarean anesthesia, hypotension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: We didn't have enough financial support
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Instituto Materno Infantil Prof. Fernando FigueiraUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Jul 2014 (estimated)
- First posted
- 13 Oct 2011 (estimated)
- 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.
Anesthesia for cesarean section has been a great challenge for the anesthesiologist, for mother and fetus are closely related. So the challenge is to anesthetize the mother without interfering with the physiology of the fetus. The spinal block, although safe, are not free of complications if not treated properly, may be responsible for increased fetal morbidity. Among the major side effects, there is hypotension, with potentially serious consequences for the maternal-fetal dyad. Hypotension in pregnant women at low risk may not lead to major damage, but a pregnant woman with low reserves, as is the case of pregnant women with pre-eclampsia, any drop in blood pressure of the mother can bring harm to the welfare of mother and fetus. Based on the above, the purpose of this study is to compare the effects of maternal and perinatal treatment of hypotension with ephedrine or metaraminol in pregnant women with severe preeclampsia undergoing cesarean section under spinal anesthesia. There will be a randomized, double-blind, which will be included pregnant women with severe preeclampsia with indication of cesarean section, gestational age above 34 weeks gestation and only.Will be Excluded women with hemorrhagic syndromes of pregnancy, HELLP syndrome, eclampsia, cardiovascular or cerebrovascular disease, fetal distress and absolute contraindications to spinal anesthesia.
All patients are fully informed of the research objectives and will only be included in the study if they agree to participate and sign the Instrument of Consent. The project was designed following the recommendations of Resolution 196/96 of the National Health and the Declaration of Helsinki for research involving human subjects (2000). In addition, the project was submitted to the Ethics Committee in Research of the Institute of Integrative Medicine Professor Fernando Figueira, is approved. The study will be conducted from June 2011 to July 2012. The study variables are: consumption of metaraminol and ephedrine before and after birth, the occurrence of nausea and vomiting, incidence of maternal hypotension, the occurrence of reactive hypertension, occurrence of bradycardia, pH of umbilical cord, Apgar score 5 minutes, need for face mask ventilation and ICU admission.
Detailed description
Ephedrine, a long time was considered the safest drug for both mother and fetus during the treatment of hypotension in Caesarean section. However, recent evidence shows that contrary to what was thought, ephedrine appears to increase fetal metabolism, decreasing the pH and excess base.
Recently, phenylephrine has been used in the treatment of hypotension during cesarean delivery with better results in relation to acid-base parameters in umbilical cord blood. However, few data are available on the use of phenylephrine in high-risk pregnancy, the majority of studies in healthy pregnant women for elective caesarean section.
Although little scientific evidence regarding the use of metaraminol for treatment of hypotension in Caesarean section, recent study demonstrated superiority of this drug compared to ephedrine, checking a lower incidence of neonatal acidosis and better control of blood pressure. The researchers also found differences in blood gases from the umbilical cord between the ephedrine and metaraminol groups larger than those already found in previous studies comparing ephedrine and phenylephrine.
The pathophysiological changes in patients with pre-eclampsia can lead to intrauterine growth restriction with chronic fetal distress, due to the limited uteroplacental flow, which, in certain situations, may be reduced by 50% to 70%. Added to this, spinal anesthesia may cause sudden hypotension and fetal acidosis more often, even in elective operations, compared to epidural or general anesthesia, and that these changes may not have clinical significance in healthy fetuses at term, but may be critical in situations where arterial insufficiency uteroplacental and fetal distress already to present. It is believed, therefore, important that treat or prevent hypotension in patients with severe preeclampsia under spinal anesthesia.
Prevention of hypotension in patients with severe preeclampsia does not require large amounts of intravenous fluids, but careful prophylaxis of postural hypotensive syndrome. Despite the care, if hypotension occurs, aggressive treatment is mandatory in these patients and fast in order to avoid worsening fetal distress and neonatal depression. Such patients are more sensitive to vasopressors, therefore, small doses should be administered.
However, the biggest challenge of the anesthesiologist is to determine the ideal vasopressor in pregnant women at high risk, able to adequately restore blood pressure levels without determining deterioration of fetal status.
30 Reynolds and Seed in 2005 showed that ephedrine, administered in large doses, has contributed to the adverse effects of spinal anesthesia (greater degree of fetal metabolic acidosis), supporting the idea that ephedrine is not the vasopressor of choice for treatment of maternal hypotension during cesarean section.
As a result, this study is to fill this knowledge gap, taking on great importance to evaluate maternal and perinatal outcomes of pregnant women with severe preeclampsia to receive ephedrine or metaraminol for treatment of maternal hypotension during caesarean section under spinal anesthesia. Considering the importance of creating a protocol, since the metaraminol, unlike phenylephrine, is widely available at our facility.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Severe preeclampsia with indication of cesarean section
- Informed consent for study participation
- Age above 34 weeks gestational
- Single Pregnancy
Key exclusion criteria (6 listed)
- Hemorrhagic syndromes of pregnancy (placenta previa, DPPNI)
- Help Syndrome
- Eclampsia
- Cardiovascular or Cerebrovascular Disease
- Fetal distress Absolute contraindications to spinal anesthesia (coagulopathy, sepsis and hypovolemia)
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 |
|---|---|---|
| MetaraminolAlso: AraminIt will be used a dose of 0.5 mg to any fall in blood pressure of the fetus until birth | Drug | – |
| EphedrineAlso: EphedrinIt will be used at any one dose de1mg fall in blood pressure of the fetus until birth | Drug | – |
Primary outcome
Incidence of maternal hypotension
Time frame: During the caesarean, on average during the first 30 minutes after spinal anesthesia
Participants are accompanied throughout their cesarean section an average of 30 minutes, where they will be measured blood pressure and heart rate every three minutes until the end of cesarean section.
1 secondary outcome
Maternal and Neonatal outcomes
Time frame: During the cesarean section and postpartum until discharge (an average of 24 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 7 Sep 2016.
- Individual participant dataSharing planned: Yes. We don't have data to share
Related trials for Preeclampsia
Recruiting
Exercise to Improve Heart and Metabolic Health After Childbirth in Women at High Risk for Preeclampsia
Postpartum Exercise, Cardiometabolic Health
RecruitingObservational study
Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Preeclampsia
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruitingPhase 2
Furosemide vs Placebo in Severe Preeclampsia Postpartum
Severe Preeclampsia
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.
Antonio Monteiro, MD study director
Instituto de Medicina integral Professor Fernando Figueira
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metaraminol and Ephedrine in people with Preeclampsia and Pregnancy Toxemias, run by Instituto Materno Infantil Prof. Fernando Figueira at 1 site in Brazil.
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 4 inclusion and 6 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 7 Sep 2016. 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 Brazil. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Incidence of maternal hypotension (time frame: During the caesarean, on average during the first 30 minutes after spinal anesthesia). 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 7 Sep 2016.