Appropriate Dosage of Vasopressor in Neonates and Infants

NCT06257316 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2312-009-1489
• Study Type: interventional
• Target: 132
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this study, the investigators will evaluate cerebral blood flow before and after drug infusion using ultrasound to suggest blood pressure criteria and dosage of ephedrine, a vasopressor, to maintain adequate cerebral blood flow in neonates and infants undergoing surgery and anesthesia.

Conditions

Hypotension; Neonatal Hypotension; Intraoperative Complications

Outcome Measures

Primary Outcomes (1)

• Recovery of cerebral blood flow within 10 minutes

  Whether at least one of the peak systolic velocity, end diastolic velocity, or velocity time integral of the internal carotid blood flow recovers to at least 80% of the baseline value within 10 minutes of the bolus injection.

  within 10 minutes after ephedrine injection

Secondary Outcomes (7)

• Recovery of cerebral blood flow within 2 minutes

  within 2 minutes after ephedrine injection

• Recovery of cerebral blood flow within 5 minutes

  within 5 minutes after ephedrine injection

• Recovery of mean arterial pressure within 10 minutes

  within 10 minutes after ephedrine injection

• Additional durg dose

  within 10 minutes after ephedrine injection

• electroencephalogram

  from the induction of anesthesia to initiation of surgery

Study Arms (6)

0.1mg/kg of ephedrine

ACTIVE COMPARATOR

If the mean arterial pressure decreases by more than 20% from baseline after induction of anesthesia and infusion of fluids until the start of surgery, a randomized dose of ephedrine will be administered. Six single doses were evaluated using six cohorts (N=20 per cohort). Subjects received single doses of ephedrine intravenously: 0.1, 0.2, 0.3, 0.5, 1.0, 1.2 mg/kg. Initially, 3 cohorts received the study drug at a given dose, after assessing the safety of ephedrine by the Korean Ministry of Food and Drug Safety, the additional 60 subjects in 3 cohorts received the study drug.

Drug: EPHEDrine Hydrochloride 5 mg/ml

0.2mg/kg of ephedrine

ACTIVE COMPARATOR

If the mean arterial pressure decreases by more than 20% from baseline after induction of anesthesia and infusion of fluids until the start of surgery, a randomized dose of ephedrine will be administered. Six single doses were evaluated using six cohorts (N=20 per cohort). Subjects received single doses of ephedrine intravenously: 0.1, 0.2, 0.3, 0.5, 1.0, 1.2 mg/kg. Initially, 3 cohorts received the study drug at a given dose, after assessing the safety of ephedrine by the Korean Ministry of Food and Drug Safety, the additional 60 subjects in 3 cohorts received the study drug.

Drug: EPHEDrine Hydrochloride 5 mg/ml

0.3mg/kg of ephedrine

ACTIVE COMPARATOR

If the mean arterial pressure decreases by more than 20% from baseline after induction of anesthesia and infusion of fluids until the start of surgery, a randomized dose of ephedrine will be administered. Six single doses were evaluated using six cohorts (N=20 per cohort). Subjects received single doses of ephedrine intravenously: 0.1, 0.2, 0.3, 0.5, 1.0, and 1.2 mg/kg. Initially, 3 cohorts received the study drug at a given dose, after assessing the safety of ephedrine by the Korean Ministry of Food and Drug Safety, the additional 60 subjects in 3 cohorts received the study drug.

Drug: EPHEDrine Hydrochloride 5 mg/ml

0.5mg/kg of ephedrine

ACTIVE COMPARATOR

If the mean arterial pressure decreases by more than 20% from baseline after induction of anesthesia and infusion of fluids until the start of surgery, a randomized dose of ephedrine will be administered. Six single doses were evaluated using six cohorts (N=20 per cohort). Subjects received single doses of ephedrine intravenously: 0.1, 0.2, 0.3, 0.5, 1.0, and 1.2 mg/kg. Initially, 3 cohorts received the study drug at a given dose, after assessing the safety of ephedrine by the Korean Ministry of Food and Drug Safety, the additional 60 subjects in 3 cohorts received the study drug.

Drug: EPHEDrine Hydrochloride 5 mg/ml

1.0mg/kg of ephedrine

ACTIVE COMPARATOR

If the mean arterial pressure decreases by more than 20% from baseline after induction of anesthesia and infusion of fluids until the start of surgery, a randomized dose of ephedrine will be administered. Six single doses were evaluated using six cohorts (N=20 per cohort). Subjects received single doses of ephedrine intravenously: 0.1, 0.2, 0.3, 0.5, 1.0, and 1.2 mg/kg. Initially, 3 cohorts received the study drug at a given dose, after assessing the safety of ephedrine by the Korean Ministry of Food and Drug Safety, the additional 60 subjects in 3 cohorts received the study drug.

Drug: EPHEDrine Hydrochloride 5 mg/ml

1.2mg/kg of ephedrine

ACTIVE COMPARATOR

If the mean arterial pressure decreases by more than 20% from baseline after induction of anesthesia and infusion of fluids until the start of surgery, a randomized dose of ephedrine will be administered. Six single doses were evaluated using six cohorts (N=20 per cohort). Subjects received single doses of ephedrine intravenously: 0.1, 0.2, 0.3, 0.5, 1.0, and 1.2 mg/kg. Initially, 3 cohorts received the study drug at a given dose, after assessing the safety of ephedrine by the Korean Ministry of Food and Drug Safety, the additional 60 subjects in 3 cohorts received the study drug.

Drug: EPHEDrine Hydrochloride 5 mg/ml

Interventions

EPHEDrine Hydrochloride 5 mg/ml DRUG

In the present study, the expected rate of recovery of the internal carotid artery according to the dose of the inotropic agent was similar to that in a previous study in which the fraction maintaining mean arterial pressure within 80% of baseline by dose of inotropic agent was 0.9% for the ephedrine 0.1, 0.6, 0.8, 1. 0, 1.2, and 1.4 doses (mg/kg) were 9.9%, 21%, 41%, 47%, 65.5%, and 40%, respectively (Br J Anaesth. 2023 May;130(5):603-610), and it was assumed that the rate of internal carotid artery recovery by inotrope dose would be 90% of that result. The study will randomize to dose in six cohorts and will include dose group and cohort variables in a logistic regression model to assess the trend between inotropic dose and rate of carotid revascularization after correcting for cohort effects on the outcome variable.

0.1mg/kg of ephedrine; 0.2mg/kg of ephedrine; 0.3mg/kg of ephedrine; 0.5mg/kg of ephedrine; 1.0mg/kg of ephedrine; 1.2mg/kg of ephedrine

Eligibility Criteria

• Age: Up to 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns and infants under 2 years of age undergoing surgery under general anesthesia at Seoul National University Hospital

You may not qualify if:

• Premature infants with a gestational age of less than 37 weeks
• Children with a history of brain disease (hydrocephalus, brain tumor, etc.)
• Patients with a history of hypoxic/ischemic brain injury
• Children with fused fontanels
• Children with uncorrected congenital cardiac malformations such as patent ductus arteriosus
• Patients with hypersensitivity to ephedrine and its components
• Patients with hypertension
• Patients with thyrotoxicosis
• Patients with renal impairment and those taking thyroid medication
• Glaucoma patients
• Diabetic patients
• Patients with prostatic hyperplasia
• Patients with chromophobe cell tumors
• Patients taking or within 2 weeks of discontinuing monoamine oxidase inhibitors
• Patients with ischemic heart disease

Sponsors & Collaborators

• Seoul National University Hospital: lead

MeSH Terms

Conditions

Hypotension; Intraoperative Complications

Interventions

Ephedrine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines

Study Officials

• Eun-Hee Kim, M.D., Ph.D.

  Seoul National University Hospital

  STUDY CHAIR

Central Study Contacts

Eun-Hee Kim, M.D., Ph.D.

CONTACT

+82-2-2072-3664; beloveun@snuh.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical associate professor

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: February 15, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: February 15, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share