Healthy VolunteersNCT02252627
The Effect of Phenylephrine and Ephedrine on Microvascular Blood Flow
An observational study of Healthy Volunteers, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
During operations to treat abdominal problems the blood pressure can fall, resulting in falls in blood flow to the vital organs. This fall can be treated by the administration of drugs that cause constriction of blood vessels. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Administration of phenylephrine, Measurement of stroke volume and Contrast enhanced ultrasound scan
- Type of treatment
- Injection or infusion
- How many people
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2014to Aug 2015
- Phase
- Observational
- 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 60 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: Healthy male volunteers
Who may be able to join
- Aged 18-60 years
- Male
- Able to consent in English by themselves
- Absence of any exclusion criteria
Who cannot join
- A BMI < 20 or > 28 kg•m2
- Active cardiovascular disease: uncontrolled hypertension (BP > 140/90), angina, heart failure (class III/IV), arthymia, right to left cardiac shunt or recent cardiac event
- Individuals taking alpha or beta-adrenergic blocking agents, monoamine oxidase inhibitors, tricyclic antidepressants, serotonin or noradrenaline selective reuptake inhibitors, quinidine, cardiac glycosides or buspirone (or who have ceased taking them in the previous 14 days¬)
- Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)
- Peripheral vascular disease
- Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes
Show all 16Show fewer
- Active inflammatory bowel disease, or renal disease
- Known prostatic hypertrophy
- Malignancy
- Clotting dysfunction
- Previous oesophageal surgery
- Individuals with a known history of oesophageal varices
- Individuals with a known history of epistaxis
- Family history of early (<55y) death from cardiovascular disease
- Known sensitivity to SonoVue, ephedrine or phenylephrine
- Participants who have taken part in any other research study in the last three months which involved: taking a drug; being paid a disturbance allowance; having an invasive procedure (eg blood sample >50ml, muscle biopsies) or exposure to ionising radiation.
Trial locations and contacts
1 site in 1 country.
John P Williams, PhD contact
United Kingdom1 site, 1 recruiting
- Recruiting
University of Nottingham, School of Medicine, Division of Medical Sciences and Graduate Entry Medicine
Derby, Derbyshire, DE22 3DT
David Read, BMBS, dread1@nhs.net
John P Williams, PhD
About this study
Official title: An Observational Study to Test the Effect of the Vasoactive Drugs Phenylephrine and Ephedrine on the Stroke Volume and Microvascular Blood Flow of Healthy Volunteers
During operations to treat abdominal problems the blood pressure can fall, resulting in falls in blood flow to the vital organs. This fall can be treated by the administration of drugs that cause constriction of blood vessels. Although these drugs correct falls in blood pressure, it is unclear what effect they have on blood flow from the heart and to the vital organs.
In this study of healthy volunteers we aim to better understand the changes in blood flow in both small and large vessels that occur in response to administration of these drugs. To do this we will use two different techniques of ultrasound imaging. A narrow (4-5mm) ultrasound probe will be inserted into the oesophagus via a nostril to measure blood flow in a major blood vessel. A second probe will rest on the abdomen and will record changes in blood flow in small vessels of the liver. Two drugs which raise the blood pressure via different mechanisms will be administered and the changes in flow from the heart and to vital organs will be measured and compared.
Read the detailed description
Optimising the cardiac output is essential to ensure adequate organ perfusion in patients who are undergoing major surgery. To enable this cardiac output (CO) is frequently monitored during operations using a variety of techniques; one such technique is trans-oesophageal Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of CO is a less invasive technique than many currently used methods, and has recently been recommended by NICE for adoption in clinical practice. The matching of microvascular blood flow and CO is advantageous for visceral organs, in marrying demands for oxygen and nutrients to their delivery. Major surgery and the attendant requirement for general anaesthesia can result in dramatic changes in blood pressure (BP) and CO. These changes can be corrected by the administration of vasoactive drugs such as phenylephrine and ephedrine, although it is unclear what effects these drugs have on microvascular blood flow (MVBF) to the intra-abdominal viscera. Whilst they correct falls in BP, and hence may increase visceral flow, this increased BP is partially mediated via splanchnic vasoconstriction, which may result in decreased blood flow. A greater appreciation of the effect of these vasoactive drugs on the CO and MVBF may help with the development of more refined algorithms for their use in the clinical setting. In our clinical physiology laboratories we regularly employ contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to measure MVBF in healthy males following a variety of physiological challenges. This minimally invasive ultrasound based imaging technique is ideal for gaining an insight into the effect various physiological interventions have on tissue blood flow and could be readily used to chart changes in visceral MVBF and CO following vasoactive drug administration. Transference of this investigative approach to a clinical setting has the potential to greatly improve the care of the surgical patient under anaesthesia.
- Conditions
- Healthy Volunteers
- Being tested
- Administration of phenylephrine, Measurement of stroke volume, Contrast enhanced ultrasound scan, Administration of ephedrine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of phenylephrineDrug
Intravenous phenylephrine will be administered in 50-100 microgram increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 1mg has been administered.
Measurement of stroke volumeOther
The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor
Contrast enhanced ultrasound scanOther
Microvascular blood flow will be measured using a contrast enhanced ultrasound scan
Administration of ephedrineDrug
Intravenous ephedrine will be administered in 3-6mg increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 30mg has been administered.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Healthy volunteers Receives: Drug: Administration of phenylephrine; Other: Measurement of stroke volume; Other: Contrast enhanced ultrasound scan; Drug: Administration of ephedrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in microvascular blood flow
Microvascular visceral blood flow is assessed using contrast enhanced ultrasound, and will be assessed before and after the administration of each drug.
Measured: 30 minutes
Secondary outcomes (1)
Change in stroke volume
The change in stroke volume will be assessed using an Oesophageal Doppler Monitor, and will be assessed before and after the administration of each drug.
Measured: 30 mins
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2014 (estimated)
- Study startAug 2014
- Primary completionAug 2015 (estimated)
- Study completionAug 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John P Williams, PhD, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02252627
- Sponsor's protocol ID
- H10102013
- Status last verified
- Jan 2015
- First submitted
- 25 Sep 2014
- Last updated
- 27 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study to Test the Effect of the Vasoactive Drugs Phenylephrine and Ephedrine on the Stroke Volume and Microvascular Blood Flow of Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02252627
- Acronym / sponsor ID
- H10102013
- Conditions
- Healthy Volunteers
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Aug 2015 (estimated)
- Study completion
- Aug 2015 (estimated)
- First posted
- 30 Sep 2014 (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.
During operations to treat abdominal problems the blood pressure can fall, resulting in falls in blood flow to the vital organs. This fall can be treated by the administration of drugs that cause constriction of blood vessels. Although these drugs correct falls in blood pressure, it is unclear what effect they have on blood flow from the heart and to the vital organs.
In this study of healthy volunteers we aim to better understand the changes in blood flow in both small and large vessels that occur in response to administration of these drugs. To do this we will use two different techniques of ultrasound imaging. A narrow (4-5mm) ultrasound probe will be inserted into the oesophagus via a nostril to measure blood flow in a major blood vessel. A second probe will rest on the abdomen and will record changes in blood flow in small vessels of the liver. Two drugs which raise the blood pressure via different mechanisms will be administered and the changes in flow from the heart and to vital organs will be measured and compared.
Detailed description
Optimising the cardiac output is essential to ensure adequate organ perfusion in patients who are undergoing major surgery. To enable this cardiac output (CO) is frequently monitored during operations using a variety of techniques; one such technique is trans-oesophageal Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of CO is a less invasive technique than many currently used methods, and has recently been recommended by NICE for adoption in clinical practice. The matching of microvascular blood flow and CO is advantageous for visceral organs, in marrying demands for oxygen and nutrients to their delivery. Major surgery and the attendant requirement for general anaesthesia can result in dramatic changes in blood pressure (BP) and CO. These changes can be corrected by the administration of vasoactive drugs such as phenylephrine and ephedrine, although it is unclear what effects these drugs have on microvascular blood flow (MVBF) to the intra-abdominal viscera. Whilst they correct falls in BP, and hence may increase visceral flow, this increased BP is partially mediated via splanchnic vasoconstriction, which may result in decreased blood flow. A greater appreciation of the effect of these vasoactive drugs on the CO and MVBF may help with the development of more refined algorithms for their use in the clinical setting. In our clinical physiology laboratories we regularly employ contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to measure MVBF in healthy males following a variety of physiological challenges. This minimally invasive ultrasound based imaging technique is ideal for gaining an insight into the effect various physiological interventions have on tissue blood flow and could be readily used to chart changes in visceral MVBF and CO following vasoactive drug administration. Transference of this investigative approach to a clinical setting has the potential to greatly improve the care of the surgical patient under anaesthesia.
Study design
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Drug: Administration of phenylephrine, Other: Measurement of stroke volume, Other: Contrast enhanced ultrasound scan, Drug: Administration of ephedrineHealthy volunteers |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy male volunteers
Key inclusion criteria (4 listed)
- Aged 18-60 years
- Male
- Able to consent in English by themselves
- Absence of any exclusion criteria
Key exclusion criteria (16 listed)
- A BMI < 20 or > 28 kg•m2
- Active cardiovascular disease: uncontrolled hypertension (BP > 140/90), angina, heart failure (class III/IV), arthymia, right to left cardiac shunt or recent cardiac event
- Individuals taking alpha or beta-adrenergic blocking agents, monoamine oxidase inhibitors, tricyclic antidepressants, serotonin or noradrenaline selective reuptake inhibitors, quinidine, cardiac glycosides or buspirone (or who have ceased taking them in the previous 14 days¬)
- Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)
- Peripheral vascular disease
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 |
|---|---|---|
| Administration of phenylephrineIntravenous phenylephrine will be administered in 50-100 microgram increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 1mg has been administered. | Drug | Group 1 |
| Measurement of stroke volumeThe measurement of stroke volume will be performed using an Oesophageal Doppler Monitor | Other | Group 1 |
| Contrast enhanced ultrasound scanMicrovascular blood flow will be measured using a contrast enhanced ultrasound scan | Other | Group 1 |
| Administration of ephedrineIntravenous ephedrine will be administered in 3-6mg increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 30mg has been administered. | Drug | Group 1 |
Primary outcome
Change in microvascular blood flow
Time frame: 30 minutes
Microvascular visceral blood flow is assessed using contrast enhanced ultrasound, and will be assessed before and after the administration of each drug.
1 secondary outcome
Change in stroke volume
Time frame: 30 mins
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2015.
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Screening Protocol
Pain
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.
John P Williams, PhD contact
John P Williams, PhD principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy Volunteers, run by University of Nottingham 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 4 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 27 Jan 2015. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact John P Williams, PhD (john.williams7@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in microvascular blood flow (time frame: 30 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 27 Jan 2015.