EPHEDRINE: Determination of the Optimal Dose of Ephedrine in Intraoperative Arterial Hypotension of Newborns and Infants up to 6 Months of Age.

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT02384876

Collaborator

(none)

120

Enrollment

Locations

Arms

63.2

Actual Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Intraoperative Arterial Hypotension Infant, Newborn	Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Jun 1, 2015

Actual Primary Completion Date :

Sep 5, 2020

Actual Study Completion Date :

Sep 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ephedrine, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG Dose escalation: 6 successive cohorts with a maximal increasing dose	Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG
Active Comparator: Ephedrine, dose : 0.1 mg/kG, reference dose Reference dose	Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.

Arm

Intervention/Treatment

Experimental: Ephedrine, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG

Dose escalation: 6 successive cohorts with a maximal increasing dose

Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.6, 0.8, 1.0, 1.2 and 1.4 mg/kG

Active Comparator: Ephedrine, dose : 0.1 mg/kG, reference dose

Reference dose

Drug: Ephedrine 30mg/10mL injectable solution, single administration, dose : 0.1 mg/kG.

Outcome Measures

Primary Outcome Measures

Therapeutic success is defined as a mBP superior to 55% of the basal mBP (prior to anesthesia) within 10 minutes post Ephedrine administration [Continuous monitoring within 10 minutes post-administration]

Secondary Outcome Measures

Return to a mBP superior to 38mmHg within 10 minutes post Ephedrine administration [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 [Continuous monitoring within 10 minutes post-administration]
Tolerance of Ephedrine: occurrence of serious adverse events [During 3 days post-administration]
Clinical examination focusing specifically on heart rate and hypertension

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 6 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hôpital d'Estaing	Clermont-Ferrand	France	63003
2	Hospices Civils de Lyon	Lyon	France
3	Hôpital Nord	Saint Etienne	France	42055

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

Principal Investigator: Mathilde de Queiroz Siqueira, MD, Service d'anesthésie pédiatrique et obstétricale, Hôpital Femme Mère Enfant, 59 boulevard Pinel - 69 677 BRON Cedex