Spinal AnesthesiaPhase 4NCT01243970
Ephedrine vs Phenylephrine - ECG Changes
A Phase 4 study testing Phenylephrine and Ephedrine in people with Spinal Anesthesia and Pregnancy, run by University College London Hospitals at 1 site in United Kingdom.
Trial summary
ECG changes during caesarean section are common. Incidence of ST depression on the ECG is up to 81% in some studies. Although this may indicate inadequate oxygen supply to the heart muscle (myocardial ischaemia) many other theories have been suggested including air entering the circulation from the placental bed, high… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Spinal Anesthesia, Pregnancy
- What is being tested?
- Phenylephrine and Ephedrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2012to Jan 2016
- Phase
- Phase 4
- 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 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Able to give written informed consent
- >37/40 weeks gestation
- Singleton pregnancy
- Elective caesarean section under spinal anaesthesia
- In good general health (American Society of Anesthesiology Category 1 or 2, fit and well or with mild systemic disease that has no impact on physical activity )
Who cannot join
- Circulatory disease (eg pre-existing hypertension)
- Cardiac disease/medications (e.g. angina, cardiomyopathy, B Blocker medication)
- Pregnancy related disease (eg pre-eclampsia)
- Diabetes pre-existing the pregnancy
- Hyperthyroidism
- Renal Disease
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- Closed-angle glaucoma
- Patients on monoamine oxidase inhibitors
- In active labour
- Emergency caesarean section
- Fetal abnormalities
- Contraindications to spinal anaesthesia
- Height >6 feet/180cm / Height <5 feet/150cm
- Body mass index (BMI) <19 or >35
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University College London Hospital
London, NW1 2BU
About this study
Official title: Randomised, Double-blind, Phase IV Study to Compare the Incidence of ECG Changes During Elective Caesarean Section Under Spinal Anaesthesia When Using Phenylephrine or Ephedrine Infusion to Maintain Baseline Systolic Blood Pressure
ECG changes during caesarean section are common. Incidence of ST depression on the ECG is up to 81% in some studies. Although this may indicate inadequate oxygen supply to the heart muscle (myocardial ischaemia) many other theories have been suggested including air entering the circulation from the placental bed, high heart rate, hormone or nervous system influences and spasm of the coronary blood supply. Perioperative ST depression often reflects an imbalance between heart muscle oxygen supply and demand. At the time of delivery, high heart rate is common and there is a further increase in the amount of blood the heart has to pump every minute due to blood coming back to the circulation from the placental bed. This increases oxygen demand and most ST changes are seen at the time of delivery or within 30 minutes. The clinical significance of these changes is much debated, and apart from a few case reports do not appear to be associated with poor heart muscle function or ischaemia (lack of oxygen supply). Management of the mother's blood pressure during caesarean section has changed greatly in recent years. Intermittent boluses of ephedrine, given when blood pressure is low, have been replaced with prevention of low blood pressure and phenylephrine has become the drug of choice. Ephedrine increases heart rate and contractility of the heart muscle and is likely to increase oxygen demand. Phenylephrine reduces heart rate while maintaining blood pressure which may result in a more favorable oxygen supply demand ratio.
The investigators aim to compare the incidence of ECG changes if the mother's blood pressure is maintained with phenylephrine as compared to ephedrine. To see if these ECG changes are associated with myocardial ischaemia, the investigators will perform troponin T analysis after delivery. Troponin T is a molecule released by ischaemic heart muscle.
- Conditions
- Spinal Anesthesia, Pregnancy
- Being tested
- Phenylephrine, Ephedrine
- Keywords
- Spinal anaesthesia, phenylephrine, ephedrine, ECG changes, Caesarean delivery, Myocardial ischaemia, Cardiac output, hypotension
- Medical subject headings
- Coronary Artery Disease, Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenylephrineDrug
Infusion dose 50 mcg / minute. On/off regimen in response to blood pressure (BP) readings every minute. Approximative 30 minutes treatment duration. Total dose 50 mcg - 1500 mcg *
- We will start the infusion after the spinal anaesthetic (see trial design), and while we will monitor cardiac output and BP (for 20 minutes) the surgeons will prep the patient (surgery not started yet). Birth should occur more or less 10-15 minutes after beginning surgery, so this is approximatively 30 minutes after spinal anaesthetic. It is very unlikely that the infusion will run continuously and exceed 1500 mcg.
EphedrineDrug
Infusion dose 4mg / minute. On/off regimen in response to blood pressure readings every minute. Approximative 30 minutes treatment duration. Total dose 4 mg - 120 mg. *
- We will start the infusion after the spinal anaesthetic(see trial design), and while we will monitor cardiac output and BP (for 20 minutes) the surgeons will prep the patient (surgery not started yet). Birth should occur more or less 10-15 minutes after beginning surgery, so this is approximatively 30 minutes after spinal anaesthetic. It is very unlikely that the infusion will run continuously and exceed 120mg.
| Study group | Role | What they receive |
|---|---|---|
| phenylephrine infusion | Active comparator | Not described Receives: Drug: Phenylephrine |
| Ephedrine infusion | Active comparator | Not described Receives: Drug: Ephedrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
ST segment changes on Holter monitoring
Measured: 30 minutes pre spinal anaesthesia to 4 hours post delivery
Secondary outcomes (3)
Troponin levels
Measured: 24h post delivery
Incidence of maternal low systolic blood pressure
Measured: 20 minutes post spinal and 30 minutes post delivery
Maternal cardiac output
Measured: 20 minutes post spinal and one measure at 5 minutes post delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2010 (estimated)
- Study startApr 2012
- Primary completionJan 2016
- Study completionJan 2016
Why it stopped: Change in clinical practice since the start of the trial in 2011 (phenylephrine superior)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal AnesthesiaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College London Hospitals
- Sponsor type
- University, hospital or other
- Collaborators
- Obstetric Anaesthetists' Association United Kingdom
- Responsible party
- Principal investigator, Roshan Fernando, University College London Hospitals
- Investigators
- Roshan Fernando, FRCA, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01243970
- Sponsor's protocol ID
- 08/0182
- Status last verified
- Oct 2016
- First submitted
- 18 Nov 2010
- Last updated
- 26 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Double-blind, Phase IV Study to Compare the Incidence of ECG Changes During Elective Caesarean Section Under Spinal Anaesthesia When Using Phenylephrine or Ephedrine Infusion to Maintain Baseline Systolic Blood Pressure
- ClinicalTrials.gov ID
- NCT01243970
- Acronym / sponsor ID
- 08/0182
- Conditions
- Spinal Anesthesia, Pregnancy
- Keywords
- Spinal anaesthesia, phenylephrine, ephedrine, ECG changes, Caesarean delivery, Myocardial ischaemia, Cardiac output, hypotension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Change in clinical practice since the start of the trial in 2011 (phenylephrine superior)
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University College London HospitalsUniversity, hospital or other
- Collaborators
- Obstetric Anaesthetists' Association United Kingdom
- Study start
- Apr 2012
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 19 Nov 2010 (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.
ECG changes during caesarean section are common. Incidence of ST depression on the ECG is up to 81% in some studies. Although this may indicate inadequate oxygen supply to the heart muscle (myocardial ischaemia) many other theories have been suggested including air entering the circulation from the placental bed, high heart rate, hormone or nervous system influences and spasm of the coronary blood supply. Perioperative ST depression often reflects an imbalance between heart muscle oxygen supply and demand. At the time of delivery, high heart rate is common and there is a further increase in the amount of blood the heart has to pump every minute due to blood coming back to the circulation from the placental bed. This increases oxygen demand and most ST changes are seen at the time of delivery or within 30 minutes. The clinical significance of these changes is much debated, and apart from a few case reports do not appear to be associated with poor heart muscle function or ischaemia (lack of oxygen supply). Management of the mother's blood pressure during caesarean section has changed greatly in recent years. Intermittent boluses of ephedrine, given when blood pressure is low, have been replaced with prevention of low blood pressure and phenylephrine has become the drug of choice. Ephedrine increases heart rate and contractility of the heart muscle and is likely to increase oxygen demand. Phenylephrine reduces heart rate while maintaining blood pressure which may result in a more favorable oxygen supply demand ratio.
The investigators aim to compare the incidence of ECG changes if the mother's blood pressure is maintained with phenylephrine as compared to ephedrine. To see if these ECG changes are associated with myocardial ischaemia, the investigators will perform troponin T analysis after delivery. Troponin T is a molecule released by ischaemic heart muscle.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| phenylephrine infusion | Active comparator | Drug: Phenylephrine |
| Ephedrine infusion | Active comparator | Drug: Ephedrine |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Able to give written informed consent
- >37/40 weeks gestation
- Singleton pregnancy
- Elective caesarean section under spinal anaesthesia
- In good general health (American Society of Anesthesiology Category 1 or 2, fit and well or with mild systemic disease that has no impact on physical activity )
Key exclusion criteria (14 listed)
- Circulatory disease (eg pre-existing hypertension)
- Cardiac disease/medications (e.g. angina, cardiomyopathy, B Blocker medication)
- Pregnancy related disease (eg pre-eclampsia)
- Diabetes pre-existing the pregnancy
- Hyperthyroidism
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 |
|---|---|---|
| PhenylephrineInfusion dose 50 mcg / minute. On/off regimen in response to blood pressure (BP) readings every minute. Approximative 30 minutes treatment duration. Total dose 50 mcg - 1500 mcg * * We will start the infusion after the spinal anaesthetic (see trial design), and while we will monitor cardiac output and BP (for 20 minutes) the surgeons will prep the patient (surgery not started yet). Birth should occur more or less 10-15 minutes after beginning surgery, so this is approximatively 30 minutes after spinal anaesthetic. It is very unlikely that the infusion will run continuously and exceed 1500 mcg. | Drug | phenylephrine infusion |
| EphedrineInfusion dose 4mg / minute. On/off regimen in response to blood pressure readings every minute. Approximative 30 minutes treatment duration. Total dose 4 mg - 120 mg. * * We will start the infusion after the spinal anaesthetic(see trial design), and while we will monitor cardiac output and BP (for 20 minutes) the surgeons will prep the patient (surgery not started yet). Birth should occur more or less 10-15 minutes after beginning surgery, so this is approximatively 30 minutes after spinal anaesthetic. It is very unlikely that the infusion will run continuously and exceed 120mg. | Drug | Ephedrine infusion |
Primary outcome
ST segment changes on Holter monitoring
Time frame: 30 minutes pre spinal anaesthesia to 4 hours post delivery
3 secondary outcomes
Troponin levels
Time frame: 24h post delivery
Incidence of maternal low systolic blood pressure
Time frame: 20 minutes post spinal and 30 minutes post delivery
Maternal cardiac output
Time frame: 20 minutes post spinal and one measure at 5 minutes post delivery
Results and safety
The study was stopped early (reason given: Change in clinical practice since the start of the trial in 2011 (phenylephrine superior)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
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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.
Roshan Fernando, FRCA principal investigator
University College London Hospitals
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 Phenylephrine and Ephedrine in people with Spinal Anesthesia and Pregnancy, run by University College London Hospitals at 1 site in United Kingdom.
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 14 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: stopped early, as of the sponsor's last update on 26 Oct 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 United Kingdom. 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 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?
The study was stopped early (reason given: Change in clinical practice since the start of the trial in 2011 (phenylephrine superior)). Results are not available in the source record.
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?
ST segment changes on Holter monitoring (time frame: 30 minutes pre spinal anaesthesia to 4 hours post delivery). 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 26 Oct 2016.