Arterial HypotensionPhase 4NCT03872570
Effect of Phenylephrine Versus Norepinephrine on Venous Return
A Phase 4 study testing Phenylephrine and Norepinephrine in people with Arterial Hypotension, run by Algemeen Ziekenhuis Maria Middelares at 1 site in Belgium.
Trial summary
Induction of general anesthesia often induces a decrease in the mean arterial blood pressure (MAP) caused by arterial and venous dilatation. Fluid administration is conventionally used to increase the patient's total blood volume, but is often associated with multiple adverse events such as postoperative edema. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Arterial Hypotension
- What is being tested?
- Phenylephrine and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Jun 2019to 15 Jun 2020
- 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 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult
- patients scheduled for DIEP flap surgery
Who cannot join
- unwilling or unable to grant written informed consent
- contra-indications for phenylephrine or norepinephrine
- cardiac arrhythmia
- no necessity for pharmacological blood pressure management
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
General Hospital Maria Middelares
Ghent, Oost-Vlaanderen, 9000
Alain F Kalmar, MD, PhD
About this study
Official title: Comparison of the Hemodynamic Effects of Phenylephrine and Norepinephrine in Patients Undergoing Deep Inferior Epigastric Perforator (DIEP) Flap Surgery.
Induction of general anesthesia often induces a decrease in the mean arterial blood pressure (MAP) caused by arterial and venous dilatation. Fluid administration is conventionally used to increase the patient's total blood volume, but is often associated with multiple adverse events such as postoperative edema.
Arterial hypotension can also be treated by vasopressor agents such as norepinephrine and phenylephrine which mainly increase the blood pressure by arterial vasoconstriction.
Read more
Compared to phenylephrine, norepinephrine has a shorter half-life (2 - 3 minutes) and improves the MAP by increase in cardiac contractility. In a recent study at our department it was demonstrated that besides arterial vasoconstriction, phenylephrine also improves venous return and cardiac output by venous vasoconstriction.
The aim of this study is to compare the hemodynamic effects of both vasopressor agents in patients undergoing deep inferior epigastric perforators (DIEP) flap surgery. If significant differences between both agents are demonstrated, these findings can provide an important basis for future recommendations.
Read the detailed description
In consecutive patients scheduled for DIEP flap surgery, all hemodynamic and respiratory variables are recorded electronically for subsequent off line analysis.
A systolic blood pressure of minimal 100 mmHg will be maintained during surgery by optimization of the cardiac preload and titrated norepinephrine (1.5 µg/kg/h) or phenylephrine (15 µg/kg/h) administration. Cardiac preload optimization will be based on pulse pressure variation (PPV) measurement, which is calculated by pulse contour analysis of the radial arterial pressure curve. Following the international goal-directed fluid therapy guidelines, plasmalyte will be administrated if the PPV>11%.
The tricuspid annular plane systolic excursion (TAPSE) will be measured by transthoracic echocardiography (TTE) to evaluate the inotropic effect of norepinephrine and phenylephrine. In addition, TTE will be used to measure the cardiac output to calibrate the PPV measurements.
- Conditions
- Arterial Hypotension
- Being tested
- Phenylephrine, Norepinephrine
- Keywords
- cardiac output, pulse pressure variation, fluid responsiveness, hemodynamic monitoring
- Medical subject headings
- Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenylephrineDrug
intravenous administration
NorepinephrineDrug
intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| phenylephrine | Active comparator | starts at 15 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg Receives: Drug: Phenylephrine |
| norepinephrine | Active comparator | starts at 1.5 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg Receives: Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
pulse pressure variation
the evolution of the pulse pressure variation in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
Secondary outcomes (8)
mean arterial blood pressure
the evolution of the mean arterial blood pressure in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
cardiac output
the evolution of the cardiac output in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
stroke volume (variation)
the evolution of the stroke volume (variation) in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
heart rate
the evolution of the heart rate in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
ventilation frequency
the evolution of the ventilation frequency in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
end-tidal CO2
the evolution of the end-tidal CO2 in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
tidal volume
the evolution of the tidal volume in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
TAPSE
the evolution of the tricuspid annular plane systolic excursion in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Measured: perioperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2019
- Study start1 Jun 2019
- Primary completion1 Jun 2020 (estimated)
- Study completion15 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Arterial 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 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Algemeen Ziekenhuis Maria Middelares
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Alain Kalmar, MD, PhD, Algemeen Ziekenhuis Maria Middelares
- Investigators
- Alain F Kalmar, MD, PhD, Principal investigator, Maria Middelares Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03872570
- Sponsor's protocol ID
- MMS.2019.008
- Status last verified
- Oct 2019
- First submitted
- 11 Mar 2019
- Last updated
- 11 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kalmar AF, Allaert S, Pletinckx P, Maes JW, Heerman J, Vos JJ, Struys MMRF, Scheeren TWL. Phenylephrine increases cardiac output by raising cardiac preload in patients with anesthesia induced hypotension. J Clin Monit Comput. 2018 Dec;32(6):969-976. doi: 10.1007/s10877-018-0126-3. Epub 2018 Mar 22.
PubMed 29569112O'Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2013 Dec 24;66(1):308-33. doi: 10.1124/pr.112.007203. Print 2014.
PubMed 24368739Beloeil H, Mazoit JX, Benhamou D, Duranteau J. Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth. 2005 Dec;95(6):782-8. doi: 10.1093/bja/aei259. Epub 2005 Oct 14.
PubMed 16227334Hengstmann JH, Goronzy J. Pharmacokinetics of 3H-phenylephrine in man. Eur J Clin Pharmacol. 1982;21(4):335-41. doi: 10.1007/BF00637623.
PubMed 7056280
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Hemodynamic Effects of Phenylephrine and Norepinephrine in Patients Undergoing Deep Inferior Epigastric Perforator (DIEP) Flap Surgery.
- ClinicalTrials.gov ID
- NCT03872570
- Acronym / sponsor ID
- MMS.2019.008
- Conditions
- Arterial Hypotension
- Keywords
- cardiac output, pulse pressure variation, fluid responsiveness, hemodynamic monitoring
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Algemeen Ziekenhuis Maria MiddelaresUniversity, hospital or other
- Study start
- 1 Jun 2019 (actual)
- Primary completion
- 1 Jun 2020 (estimated)
- Study completion
- 15 Jun 2020 (estimated)
- First posted
- 13 Mar 2019 (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.
Induction of general anesthesia often induces a decrease in the mean arterial blood pressure (MAP) caused by arterial and venous dilatation. Fluid administration is conventionally used to increase the patient's total blood volume, but is often associated with multiple adverse events such as postoperative edema.
Arterial hypotension can also be treated by vasopressor agents such as norepinephrine and phenylephrine which mainly increase the blood pressure by arterial vasoconstriction.
Compared to phenylephrine, norepinephrine has a shorter half-life (2 - 3 minutes) and improves the MAP by increase in cardiac contractility. In a recent study at our department it was demonstrated that besides arterial vasoconstriction, phenylephrine also improves venous return and cardiac output by venous vasoconstriction.
The aim of this study is to compare the hemodynamic effects of both vasopressor agents in patients undergoing deep inferior epigastric perforators (DIEP) flap surgery. If significant differences between both agents are demonstrated, these findings can provide an important basis for future recommendations.
Detailed description
In consecutive patients scheduled for DIEP flap surgery, all hemodynamic and respiratory variables are recorded electronically for subsequent off line analysis.
A systolic blood pressure of minimal 100 mmHg will be maintained during surgery by optimization of the cardiac preload and titrated norepinephrine (1.5 µg/kg/h) or phenylephrine (15 µg/kg/h) administration. Cardiac preload optimization will be based on pulse pressure variation (PPV) measurement, which is calculated by pulse contour analysis of the radial arterial pressure curve. Following the international goal-directed fluid therapy guidelines, plasmalyte will be administrated if the PPV>11%.
The tricuspid annular plane systolic excursion (TAPSE) will be measured by transthoracic echocardiography (TTE) to evaluate the inotropic effect of norepinephrine and phenylephrine. In addition, TTE will be used to measure the cardiac output to calibrate the PPV measurements.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| phenylephrine | Active comparator | Drug: Phenylephrinestarts at 15 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg |
| norepinephrine | Active comparator | Drug: Norepinephrinestarts at 1.5 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult
- patients scheduled for DIEP flap surgery
Key exclusion criteria (4 listed)
- unwilling or unable to grant written informed consent
- contra-indications for phenylephrine or norepinephrine
- cardiac arrhythmia
- no necessity for pharmacological blood pressure management
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 |
|---|---|---|
| Phenylephrineintravenous administration | Drug | phenylephrine |
| Norepinephrineintravenous administration | Drug | norepinephrine |
Primary outcome
pulse pressure variation
Time frame: perioperative
the evolution of the pulse pressure variation in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
8 secondary outcomes
mean arterial blood pressure
Time frame: perioperative
cardiac output
Time frame: perioperative
stroke volume (variation)
Time frame: perioperative
heart rate
Time frame: perioperative
ventilation frequency
Time frame: perioperative
end-tidal CO2
Time frame: perioperative
tidal volume
Time frame: perioperative
TAPSE
Time frame: perioperative
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2019.
- Background: PubMed 29569112Kalmar AF, Allaert S, Pletinckx P, Maes JW, Heerman J, Vos JJ, Struys MMRF, Scheeren TWL. Phenylephrine increases cardiac output by raising cardiac preload in patients with anesthesia induced hypotension. J Clin Monit Comput. 2018 Dec;32(6):969-976. doi: 10.1007/s10877-018-0126-3. Epub 2018 Mar 22.
- Background: PubMed 24368739O'Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2013 Dec 24;66(1):308-33. doi: 10.1124/pr.112.007203. Print 2014.
- Background: PubMed 16227334Beloeil H, Mazoit JX, Benhamou D, Duranteau J. Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth. 2005 Dec;95(6):782-8. doi: 10.1093/bja/aei259. Epub 2005 Oct 14.
- Background: PubMed 7056280Hengstmann JH, Goronzy J. Pharmacokinetics of 3H-phenylephrine in man. Eur J Clin Pharmacol. 1982;21(4):335-41. doi: 10.1007/BF00637623.
- 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.
Alain F Kalmar, MD, PhD principal investigator
Maria Middelares Hospital
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 Norepinephrine in people with Arterial Hypotension, run by Algemeen Ziekenhuis Maria Middelares at 1 site in Belgium.
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 2 inclusion and 4 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 11 Oct 2019. 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 Belgium. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alain F Kalmar, MD, PhD (+32 246 17 29, alain.kalmar@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pulse pressure variation (time frame: perioperative). 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 NCT03872570, which also lists 4 linked publications.
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 11 Oct 2019.