HypotensionNCT02654847
Norepinephrine To Prevent Hypotension After Spinal Anesthesia For Cesarean Delivery: A Dose Finding Study
A study testing Norepinephrine and Normal Saline in people with Hypotension, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
Spinal anesthesia is the most common anesthetic technique for elective Cesarean delivery (CD), but the most frequent unwanted side effect is hypotension, which can cause nausea and vomiting, as well as effects on the fetus. Prevention and treatment of maternal hypotension includes intravenous fluids and vasopressors. 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
- Hypotension
- What is being tested?
- Norepinephrine and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2016to Apr 2016
- Phase
- Interventional
- 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 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Elective CD under spinal anesthesia
- Normal singleton pregnancy beyond 36 weeks gestation
- ASA physical status II/III
- Weight 50-100 kg, height 150-180 cm
- Age over 18 years
- Informed consent
Who cannot join
- Patient refusal
- Allergy or hypersensitivity to norepinephrine or sulfite
- Preexisting or pregnancy-induced hypertension
- Cardiovascular or cerebrovascular disease
- Fetal abnormalities
- History of diabetes, excluding gestational diabetes
- Use of monoamine oxidase inhibitors, triptyline or imipramine antidepressants
Trial locations and contacts
1 site in 1 country.
About this study
Spinal anesthesia is the most common anesthetic technique for elective Cesarean delivery (CD), but the most frequent unwanted side effect is hypotension, which can cause nausea and vomiting, as well as effects on the fetus. Prevention and treatment of maternal hypotension includes intravenous fluids and vasopressors. Phenylephrine is the most common vasopressor used for this purpose. However, it has been shown to reduce maternal heart rate and cardiac output, which may be a concern in an already compromised fetus. Norepinephrine is commonly used in high concentrations in intensive care and recent studies have suggested that in low concentrations it may be a better alternative to phenylephrine in elective CD, as it does not reduce the maternal heart rate or cardiac output. The optimum bolus dose of norepinephrine to prevent hypotension after spinal anesthesia in elective CD has not been elucidated. The investigators propose this study to determine the dose that would be effective in 90% of patients (ED90).
A previous study by Ngan Kee et al, using continuous infusion of norepinephrine to prevent hypotension in elective CD, suggested a potency ratio for norepinephrine to phenylephrine of approximately 16:1. Hence, the investigators hypothesise that the ED90 will be approximately 6 µg, given that the current phenylephrine bolus dose at the investigators' institution is approximately 100 µg.
Read the detailed description
The use of norepinephrine to prevent and treat hypotension during cesarean delivery (CD) is new and data in the literature are scarce. A recent randomised controlled trial by Ngan Kee et al compared continuous infusions of norepinephrine and phenylephrine to prevent hypotension during CD. They showed that norepinephrine was effective at maintaining blood pressure, with a greater cardiac output and heart rate compared to phenylephrine. However, the effective bolus dose of norepinephrine needed to prevent maternal hypotension was not determined, and since this is a relatively new arena, no dose-response studies are available in the literature either. Therefore, it would be logical to establish the effective bolus dose of norepinephrine TO PREVENT HYPOTENSION during elective CD.
- Conditions
- Hypotension
- Being tested
- Norepinephrine, Normal Saline
- Keywords
- vasopressor, blood pressure, Cesarean section, spinal anesthesia
- Medical subject headings
- Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NorepinephrineDrug
Also called Norepinephrine bitartrate
Normal SalineDrug
Also called sodium chloride
0.9% sodium chloride solution, used as a diluent.
| Study group | Role | What they receive |
|---|---|---|
| Norepinephrine 3 micrograms/mL | Active comparator | 1mL of a solution of norepinephrine, containing 3 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. Receives: Drug: Norepinephrine; Drug: Normal Saline |
| Norepinephrine 4 micrograms/mL | Active comparator | 1mL of a solution of norepinephrine, containing 4 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. Receives: Drug: Norepinephrine; Drug: Normal Saline |
| Norepinephrine 5 micrograms/mL | Active comparator | 1mL of a solution of norepinephrine, containing 5 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. Receives: Drug: Norepinephrine; Drug: Normal Saline |
| Norepinephrine 6 micrograms/mL | Active comparator | 1mL of a solution of norepinephrine, containing 6 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. Receives: Drug: Norepinephrine; Drug: Normal Saline |
| Norepinephrine 7 micrograms/mL | Active comparator | 1mL of a solution of norepinephrine, containing 7 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. Receives: Drug: Norepinephrine; Drug: Normal Saline |
| Norepinephrine 8 micrograms/mL | Active comparator | 1mL of a solution of norepinephrine, containing 8 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. Receives: Drug: Norepinephrine; Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic blood pressure
The primary outcome of this study will be the success/response of the norepinephrine dose to maintain the systolic blood pressure at or above 80% of baseline, from induction of spinal anesthesia to delivery of the fetus.
Measured: 30 minutes
Secondary outcomes (15)
Presence of Nausea
Presence of nausea in patients from induction of spinal anesthesia to delivery of the fetus.
Measured: 30 minutes
Presence of Vomiting
Presence of vomiting in patients from induction of spinal anesthesia to delivery of the fetus.
Measured: 30 minutes
Hypertension: Systolic blood pressure at or above 120% of baseline
Systolic blood pressure at or above 120% of baseline, from induction of spinal anesthesia to delivery of the fetus.
Measured: 30 minutes
Bradycardia: Heart rate less than 50 bpm
Heart rate less than 50 bpm, from induction of spinal anesthesia
Measured: 30 minutes
Upper sensory level of anesthetic block, assessed by pinprick upon delivery
Upper sensory level of anesthesia, assessed by pinprick upon delivery
Measured: 30 minutes
Umbilical artery pH
Umbilical artery pH
Measured: 24 hours
Umbilical artery partial pressure of carbon dioxide
Umbilical artery partial pressure of carbon dioxide
Measured: 24 hours
Umbilical artery partial pressure of oxygen
Umbilical artery partial pressure of oxygen
Measured: 24 hours
Umbilical artery bicarbonate
Umbilical artery bicarbonate
Measured: 24 hours
Umbilical artery base excess
Umbilical artery base excess
Measured: 24 hours
Umbilical vein pH
Umbilical vein pH
Measured: 24 hours
Umbilical vein partial pressure of carbon dioxide
Umbilical vein partial pressure of carbon dioxide
Measured: 24 hours
Umbilical vein partial pressure of oxygen
Umbilical vein partial pressure of oxygen
Measured: 24 hours
Umbilical vein bicarbonate
Umbilical vein bicarbonate
Measured: 24 hours
Umbilical vein base excess
Umbilical vein base excess
Measured: 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 Jan 2016 (estimated)
- Study startJan 2016
- Primary completionMar 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypotensionStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jose CA Carvalho, MD, PhD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654847
- Sponsor's protocol ID
- 16-02
- Status last verified
- Aug 2016
- First submitted
- 5 Jan 2016
- Last updated
- 31 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.
PubMed 28248702
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Norepinephrine To Prevent Hypotension After Spinal Anesthesia For Cesarean Delivery: A Dose Finding Study
- ClinicalTrials.gov ID
- NCT02654847
- Acronym / sponsor ID
- 16-02
- Conditions
- Hypotension
- Keywords
- vasopressor, blood pressure, Cesarean section, spinal anesthesia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 13 Jan 2016 (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.
Spinal anesthesia is the most common anesthetic technique for elective Cesarean delivery (CD), but the most frequent unwanted side effect is hypotension, which can cause nausea and vomiting, as well as effects on the fetus. Prevention and treatment of maternal hypotension includes intravenous fluids and vasopressors. Phenylephrine is the most common vasopressor used for this purpose. However, it has been shown to reduce maternal heart rate and cardiac output, which may be a concern in an already compromised fetus. Norepinephrine is commonly used in high concentrations in intensive care and recent studies have suggested that in low concentrations it may be a better alternative to phenylephrine in elective CD, as it does not reduce the maternal heart rate or cardiac output. The optimum bolus dose of norepinephrine to prevent hypotension after spinal anesthesia in elective CD has not been elucidated. The investigators propose this study to determine the dose that would be effective in 90% of patients (ED90).
A previous study by Ngan Kee et al, using continuous infusion of norepinephrine to prevent hypotension in elective CD, suggested a potency ratio for norepinephrine to phenylephrine of approximately 16:1. Hence, the investigators hypothesise that the ED90 will be approximately 6 µg, given that the current phenylephrine bolus dose at the investigators' institution is approximately 100 µg.
Detailed description
The use of norepinephrine to prevent and treat hypotension during cesarean delivery (CD) is new and data in the literature are scarce. A recent randomised controlled trial by Ngan Kee et al compared continuous infusions of norepinephrine and phenylephrine to prevent hypotension during CD. They showed that norepinephrine was effective at maintaining blood pressure, with a greater cardiac output and heart rate compared to phenylephrine. However, the effective bolus dose of norepinephrine needed to prevent maternal hypotension was not determined, and since this is a relatively new arena, no dose-response studies are available in the literature either. Therefore, it would be logical to establish the effective bolus dose of norepinephrine TO PREVENT HYPOTENSION during elective CD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Norepinephrine 3 micrograms/mL | Active comparator | Drug: Norepinephrine, Drug: Normal Saline1mL of a solution of norepinephrine, containing 3 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. |
| Norepinephrine 4 micrograms/mL | Active comparator | Drug: Norepinephrine, Drug: Normal Saline1mL of a solution of norepinephrine, containing 4 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. |
| Norepinephrine 5 micrograms/mL | Active comparator | Drug: Norepinephrine, Drug: Normal Saline1mL of a solution of norepinephrine, containing 5 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. |
| Norepinephrine 6 micrograms/mL | Active comparator | Drug: Norepinephrine, Drug: Normal Saline1mL of a solution of norepinephrine, containing 6 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. |
| Norepinephrine 7 micrograms/mL | Active comparator | Drug: Norepinephrine, Drug: Normal Saline1mL of a solution of norepinephrine, containing 7 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. |
| Norepinephrine 8 micrograms/mL | Active comparator | Drug: Norepinephrine, Drug: Normal Saline1mL of a solution of norepinephrine, containing 8 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Elective CD under spinal anesthesia
- Normal singleton pregnancy beyond 36 weeks gestation
- ASA physical status II/III
- Weight 50-100 kg, height 150-180 cm
- Age over 18 years
Key exclusion criteria (7 listed)
- Patient refusal
- Allergy or hypersensitivity to norepinephrine or sulfite
- Preexisting or pregnancy-induced hypertension
- Cardiovascular or cerebrovascular disease
- Fetal abnormalities
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 |
|---|---|---|
| NorepinephrineAlso: Norepinephrine bitartrate | Drug | Norepinephrine 3 micrograms/mL, Norepinephrine 4 micrograms/mL, Norepinephrine 5 micrograms/mL, Norepinephrine 6 micrograms/mL, Norepinephrine 7 micrograms/mL, Norepinephrine 8 micrograms/mL |
| Normal SalineAlso: sodium chloride0.9% sodium chloride solution, used as a diluent. | Drug | Norepinephrine 3 micrograms/mL, Norepinephrine 4 micrograms/mL, Norepinephrine 5 micrograms/mL, Norepinephrine 6 micrograms/mL, Norepinephrine 7 micrograms/mL, Norepinephrine 8 micrograms/mL |
Primary outcome
Systolic blood pressure
Time frame: 30 minutes
The primary outcome of this study will be the success/response of the norepinephrine dose to maintain the systolic blood pressure at or above 80% of baseline, from induction of spinal anesthesia to delivery of the fetus.
15 secondary outcomes
Presence of Nausea
Time frame: 30 minutes
Presence of Vomiting
Time frame: 30 minutes
Hypertension: Systolic blood pressure at or above 120% of baseline
Time frame: 30 minutes
Bradycardia: Heart rate less than 50 bpm
Time frame: 30 minutes
Upper sensory level of anesthetic block, assessed by pinprick upon delivery
Time frame: 30 minutes
Umbilical artery pH
Time frame: 24 hours
Umbilical artery partial pressure of carbon dioxide
Time frame: 24 hours
Umbilical artery partial pressure of oxygen
Time frame: 24 hours
Umbilical artery bicarbonate
Time frame: 24 hours
Umbilical artery base excess
Time frame: 24 hours
Umbilical vein pH
Time frame: 24 hours
Umbilical vein partial pressure of carbon dioxide
Time frame: 24 hours
Umbilical vein partial pressure of oxygen
Time frame: 24 hours
Umbilical vein bicarbonate
Time frame: 24 hours
Umbilical vein base excess
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2016.
- Derived from this study: PubMed 28248702Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.
- 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.
Jose CA Carvalho, MD, PhD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Norepinephrine and Normal Saline in people with Hypotension, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
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 6 inclusion and 7 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 31 Aug 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 Canada. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Systolic blood pressure (time frame: 30 minutes). 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 NCT02654847, which also lists 1 linked publication.
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 31 Aug 2016.