Intraoperative Arterial HypotensionPhase 2EPHEDRINENCT02384876
Determination of the Optimal Dose of Ephedrine in Intraoperative Arterial Hypotension of Newborns and Infants up to 6 Months of Age.
A Phase 2 study testing Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG and Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG. in people with Intraoperative Arterial Hypotension and Infant, Newborn, run by Hospices Civils de Lyon at 3 sites in France.
Trial summary
The incidence of arterial hypotension under general anesthesia using sevoflurane is particularly high in newborns and infants up to 6 months of age. A decrease of 20% of the initial mean blood pressure (mBP) is the definition of significant arterial hypotension in adults and children. Read more about this study
- Who is it for?
- Ages Up to 6 months
- Conditions the study is for
- Intraoperative Arterial Hypotension, Infant, Newborn
- What is being tested?
- Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG and Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesFrance
- Study dates
- Jun 2015to 5 Sep 2020
- Phase
- Phase 2
- 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 Up to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newborns or infants < 6 months of age,
- boys and girls,
- premature or not,
- requiring general anesthesia induced by sevoflurane
- who presents during anesthesia a decrease of blood pressure superior to 20% of the basal mBP (measured prior to surgery) despite of vascular filling with sodium chloride 0.9% (10mL/kg during 10 min).
- Written, informed consent obtained from the 2 parents
Who cannot join
- Allergy to Ephedrine.
- Emergency surgery.
- Patient having previously received other vasopressive amines.
- Use of other indirect sympathomimetic drug such as phenylpropanolamine, phenylephrine, pseudoephedrine and methylphenidate.
- Premedication with clonidine
- Congenital heart disease
- IV-induced anesthesia.
Trial locations and contacts
3 sites in 1 country.
France3 sites
Hôpital d'Estaing
Clermont-Ferrand, 63003
Hospices Civils de Lyon
Lyon
Hôpital Nord
Saint-Etienne, 42055
About this study
Official title: Determination of the Optimal Dose of Ephedrine in Intraoperative Arterial Hypotension of Newborns and Infants up to 6 Months of Age. A Randomized, Controlled, Open-label, Dose Escalation Study.
The incidence of arterial hypotension under general anesthesia using sevoflurane is particularly high in newborns and infants up to 6 months of age. A decrease of 20% of the initial mean blood pressure (mBP) is the definition of significant arterial hypotension in adults and children. In adults, intraoperative arterial hypotension is associated with an increase of intraoperative mortality and a certain neurological morbidity. In infants under 6 months of age, neurological disorders have been reported following general anesthesia. Neurotoxicity of hypnotics is often incriminated as should be the episodes of arterial hypotension.
Current management of hypotension uses vascular filling with crystalloids and vasopressive amines in second intention. Dopamine is the most frequently used amine. Ephedrine can also be used. Ephedrine is particularly interesting because of its action on both α and β receptors and its mode of administration: one dose and peripheral access.
Read more
Only one study is available in children from birth to adulthood; it demonstrates a lower hemodynamic response in infants than in adults, when administered a low dose of Ephedrine (0.1 to 0.2 mg/kg). A recent retrospective cohort suggests an under efficacy of low doses and the use of higher doses than those recommended.
The primary objective is to determine the optimal dose of ephedrine (dose of ephedrine associated with a difference of proportion of newborns/infants in therapeutic success of 55%) compare to the reference dose of 0.1mg/kg as a first line treatment of intraoperative arterial hypotension.
Secondary objectives:
- Return to a mBP superior to 38mmHg post Ephedrine administration.
- To assess occurrence of hypoxemic events during anesthesia.
- To assess tolerance of ephedrine. One hundred and twenty newborn and infants up to 6 months of age will be recruited in 3 sites of the Rhone Alpes Auvergne area over 24 months.
- Being tested
- Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG, Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.
- Keywords
- pediatric, intraoperative arterial hypotension, ephedrine, general anesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kGDrug
Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.Drug
| Study group | Role | What they receive |
|---|---|---|
| Ephedrine, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG | Experimental | Dose escalation: 6 successive cohorts with a maximal increasing dose Receives: Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG |
| Ephedrine, dose : 0.1 mg/kG, reference dose | Active comparator | Reference dose Receives: Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic success is defined as a mBP superior to 55% of the basal mBP (prior to anesthesia) within 10 minutes post Ephedrine administration
Measured: Continuous monitoring within 10 minutes post-administration
Secondary outcomes (3)
Return to a mBP superior to 38mmHg within 10 minutes post Ephedrine administration
Measured: Continuous monitoring within 10 minutes post-administration
Variations of O2 saturation in cerebral tissue (number of desaturations, evolution under treatment) using a Near Infrared Spectroscopy (NIRS) technology
Measured: Continuous monitoring within 10 minutes post-administration
Tolerance of Ephedrine: occurrence of serious adverse events
Clinical examination focusing specifically on heart rate and hypertension
Measured: During 3 days post-administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2015 (estimated)
- Study startJun 2015
- Primary completion5 Sep 2020
- Study completion5 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intraoperative Arterial HypotensionStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mathilde de Queiroz Siqueira, MD, Principal investigator, Service d'anesthésie pédiatrique et obstétricale, Hôpital Femme Mère Enfant, 59 boulevard Pinel - 69 677 BRON Cedex
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02384876
- Sponsor's protocol ID
- 69HCL14_0248
- Other IDs
- 2014-004190-16, 2014
- Acronym
- EPHEDRINE
- Status last verified
- Aug 2025
- First submitted
- 27 Feb 2015
- Last updated
- 4 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Szostek AS, Saunier C, Elsensohn MH, Boucher P, Merquiol F, Gerst A, Portefaix A, Chassard D, De Queiroz Siqueira M. Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial. Br J Anaesth. 2023 May;130(5):603-610. doi: 10.1016/j.bja.2022.12.006. Epub 2023 Jan 12.
PubMed 36639328Szostek AS, Boucher P, Subtil F, Zerzaihi O, Saunier C, de Queiroz Siqueira M, Merquiol F, Martin P, Granier M, Gerst A, Lambert A, Storme T, Chassard D, Nony P, Kassai B, Gaillard S. Determination of the optimal dose of ephedrine in the treatment of arterial hypotension due to general anesthesia in neonates and infants below 6 months old: the ephedrine study protocol for a randomized, open-label, controlled, dose escalation trial. Trials. 2021 Mar 12;22(1):208. doi: 10.1186/s13063-021-05155-2.
PubMed 33712076
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of the Optimal Dose of Ephedrine in Intraoperative Arterial Hypotension of Newborns and Infants up to 6 Months of Age. A Randomized, Controlled, Open-label, Dose Escalation Study.
- ClinicalTrials.gov ID
- NCT02384876
- Acronym / sponsor ID
- EPHEDRINE / 69HCL14_0248
- Keywords
- pediatric, intraoperative arterial hypotension, ephedrine, general anesthesia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- 5 Sep 2020 (actual)
- Study completion
- 5 Sep 2020 (actual)
- First posted
- 10 Mar 2015 (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.
The incidence of arterial hypotension under general anesthesia using sevoflurane is particularly high in newborns and infants up to 6 months of age. A decrease of 20% of the initial mean blood pressure (mBP) is the definition of significant arterial hypotension in adults and children. In adults, intraoperative arterial hypotension is associated with an increase of intraoperative mortality and a certain neurological morbidity. In infants under 6 months of age, neurological disorders have been reported following general anesthesia. Neurotoxicity of hypnotics is often incriminated as should be the episodes of arterial hypotension.
Current management of hypotension uses vascular filling with crystalloids and vasopressive amines in second intention. Dopamine is the most frequently used amine. Ephedrine can also be used. Ephedrine is particularly interesting because of its action on both α and β receptors and its mode of administration: one dose and peripheral access.
Only one study is available in children from birth to adulthood; it demonstrates a lower hemodynamic response in infants than in adults, when administered a low dose of Ephedrine (0.1 to 0.2 mg/kg). A recent retrospective cohort suggests an under efficacy of low doses and the use of higher doses than those recommended.
The primary objective is to determine the optimal dose of ephedrine (dose of ephedrine associated with a difference of proportion of newborns/infants in therapeutic success of 55%) compare to the reference dose of 0.1mg/kg as a first line treatment of intraoperative arterial hypotension.
Secondary objectives:
- Return to a mBP superior to 38mmHg post Ephedrine administration.
- To assess occurrence of hypoxemic events during anesthesia.
- To assess tolerance of ephedrine. One hundred and twenty newborn and infants up to 6 months of age will be recruited in 3 sites of the Rhone Alpes Auvergne area over 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ephedrine, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG | Experimental | Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kGDose escalation: 6 successive cohorts with a maximal increasing dose |
| Ephedrine, dose : 0.1 mg/kG, reference dose | Active comparator | Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.Reference dose |
Who may qualify
- Ages
- Up to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Newborns or infants < 6 months of age,
- boys and girls,
- premature or not,
- requiring general anesthesia induced by sevoflurane
- who presents during anesthesia a decrease of blood pressure superior to 20% of the basal mBP (measured prior to surgery) despite of vascular filling with sodium chloride 0.9% (10mL/kg during 10 min).
Key exclusion criteria (7 listed)
- Allergy to Ephedrine.
- Emergency surgery.
- Patient having previously received other vasopressive amines.
- Use of other indirect sympathomimetic drug such as phenylpropanolamine, phenylephrine, pseudoephedrine and methylphenidate.
- Premedication with clonidine
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 |
|---|---|---|
| Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG | Drug | Ephedrine, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG |
| Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG. | Drug | Ephedrine, dose : 0.1 mg/kG, reference dose |
Primary outcome
Therapeutic success is defined as a mBP superior to 55% of the basal mBP (prior to anesthesia) within 10 minutes post Ephedrine administration
Time frame: Continuous monitoring within 10 minutes post-administration
3 secondary outcomes
Return to a mBP superior to 38mmHg within 10 minutes post Ephedrine administration
Time frame: Continuous monitoring within 10 minutes post-administration
Variations of O2 saturation in cerebral tissue (number of desaturations, evolution under treatment) using a Near Infrared Spectroscopy (NIRS) technology
Time frame: Continuous monitoring within 10 minutes post-administration
Tolerance of Ephedrine: occurrence of serious adverse events
Time frame: During 3 days post-administration
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 4 Sep 2025.
- Results publication: PubMed 36639328Szostek AS, Saunier C, Elsensohn MH, Boucher P, Merquiol F, Gerst A, Portefaix A, Chassard D, De Queiroz Siqueira M. Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial. Br J Anaesth. 2023 May;130(5):603-610. doi: 10.1016/j.bja.2022.12.006. Epub 2023 Jan 12.
- Derived from this study: PubMed 33712076Szostek AS, Boucher P, Subtil F, Zerzaihi O, Saunier C, de Queiroz Siqueira M, Merquiol F, Martin P, Granier M, Gerst A, Lambert A, Storme T, Chassard D, Nony P, Kassai B, Gaillard S. Determination of the optimal dose of ephedrine in the treatment of arterial hypotension due to general anesthesia in neonates and infants below 6 months old: the ephedrine study protocol for a randomized, open-label, controlled, dose escalation trial. Trials. 2021 Mar 12;22(1):208. doi: 10.1186/s13063-021-05155-2.
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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.
Mathilde de Queiroz Siqueira, MD principal investigator
Service d'anesthésie pédiatrique et obstétricale, Hôpital Femme Mère Enfant, 59 boulevard Pinel - 69 677 BRON Cedex
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG and Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG. in people with Intraoperative Arterial Hypotension and Infant, Newborn, run by Hospices Civils de Lyon at 3 sites in France.
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 4 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 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?
Therapeutic success is defined as a mBP superior to 55% of the basal mBP (prior to anesthesia) within 10 minutes post Ephedrine administration (time frame: Continuous monitoring within 10 minutes post-administration). 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 NCT02384876, which also lists 2 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 4 Sep 2025.