ONDANSETRON AND EFFECTIVE DOSE IN 50% OF SUBJECTS OF PROPHYLACTIC NOREPINEPHRINE INFUSIONS FOR PREVENTING SPINAL ANESTHESIA-INDUCED HYPOTENSION DURING CESAREAN DELIVERY

NCT04703088 | Unknown Phase 3

• 1 other identifier: 2021-5610
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Spinal anesthesia is the preferred technique for elective cesarean section as per ASA guidelines. Hypotension is the main complication of this technique and is secondary to both sympatholysis and its associated decrease in systemic vascular resistance and to the Bezold-Jarisch reflex, which causes hypotension and bradycardia in response to noxious stimuli detected in the cardiac ventricles. In pregnant patients, spinal anesthesia induced hypotension is worsened by compression of the aorta and inferior vena cava by the gravid uterus. In this setting, hypotension could lead to uteroplacental hypoperfusion and fetal distress. In its 2020 guidelines for enhanced recovery after cesarean section, SOAP states that preventing spinal-induced hypotension is an important strategy to enhance maternal and neonatal outcomes in cesarean delivery Recent studies showed that 5-hydroxytryptamine-3 receptor antagonists, mostly used as nausea and vomiting prophylaxis agents, also contributed to inhibit the Bezold-Jarisch reflex and its associated hemodynamic consequences. Ondansetron is the most studied molecule in this field. Many recent studies and meta-analyses show renewed interest in the use of norepinephrine as a first line agent for preventing and treating spinal anesthesia-induced hypotension in obstetric anesthesia practice instead of phenylephrine. Norepinephrine has the advantage of a better cardiac output and cardiac frequency as compared to phenylephrine without any fetal side effect. The combination of ondansetron and phenylephrine for the prevention of spinal anesthesia-induced hypotension has been studied, but not the combination of ondansetron and norepinephrine. The main objective of this study is to evaluate the sparing effect of a standard dose of ondansetron on norepinephrine consumption during elective cesarean section under spinal anesthesia by determining the effective dose in 50% of subjects (ED50) of a prophylactic norepinephrine infusion after receiving a single dose of 4 mg of ondansetron or a saline control.

Conditions

Hypotension; Anesthesia; Adverse Effect, Spinal and Epidural; Cesarean Section

Keywords

Spinal Anesthesia; Hypotension, Vascular; Ondansetron Hydrochloride; Norepinephrine; Vasoconstrictor Agents; Cesarean section; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (1)

• ED50 Norepinephrine

  The effective dose in 50% of subjects (ED50) of a prophylactic norepinephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4mg or saline control five minutes before spinal anesthesia for elective cesarean delivery

  At the fetal delivery

Secondary Outcomes (1)

• Total consumption of Norepinephrine

  At the fetal delivery

Study Arms (2)

INTERVENTION GROUP - ONDANSETRON

EXPERIMENTAL

2 mL of a solution of Ondansetron containing 2mg/ml in a 3 ml syringe will be given intravenously to a patient five minutes before positioning for induction of spinal anesthesia

Drug: Ondansetron 4 MG

CONTROL GROUP - NORMAL SALINE

PLACEBO COMPARATOR

2 mL of 0.9% Saline in a 3 ml syringe will be given intravenously to a patient five minutes before positioning for induction of spinal anesthesia

Drug: 0.9% Saline

Interventions

Ondansetron 4 MG DRUG

2 mL of a solution of Ondansetron containing 2mg/ml in a 3 ml syringe will be given intravenously to a patient five minutes before positioning for induction of spinal anesthesia

INTERVENTION GROUP - ONDANSETRON

0.9% Saline DRUG

2 mL of 0,9% Saline in a 3 ml syringe will be given intravenously to a patient five minutes before positioning for induction of spinal anesthesia

CONTROL GROUP - NORMAL SALINE

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• parturients with a singleton pregnancy at term (37 week's gestation and more)
• elective cesarean delivery under spinal anesthesia
• American Society of Anesthesiologists physical status \< III

You may not qualify if:

• patient refusal
• allergy or hypersensitivity to Norepinephrine or Ondansetron
• Use of monoamine oxidase inhibitors, triptyline or imipramine antidepressants
• Long QT syndrome or another cause of prolonged QT
• significant preexisting maternal disease (cardiovascular or cerebrovascular disease or coagulopathy, diabetes mellitus)
• pre-existing or pregnancy-induced hypertension
• pathological pregnancy (ruptured membranes, pre-eclampsia, placenta praevia, gestational diabetes)
• body mass index \< 18 or \> 40
• height \< 150 or \> 180
• fetal abnormalities
• contraindication to spinal anesthesia

Sponsors & Collaborators

• Laval University: lead
• CHU de Quebec-Universite Laval: collaborator

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MeSH Terms

Conditions

Hypotension

Interventions

Ondansetron; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Romain LANCHON

CONTACT

+1 418-525-4444; romain.lanchon@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Studied medication will be administered to the patient after randomization by the investigators (two anesthesia residents or two staff anesthesiologists) who will not be involved in subsequent anesthetic management of the patients. The investigators will also program the infusion rate of norepinephrine at the start of each case and will be the only persons aware of the assigned infusion rate. The investigators will hide the infusion rate with an opaque paper cover over the infusion display during the case. The investigators will also collect all the data during each procedures. To summarize, the anesthesiologist in charge of the patient will not know which treatment will be injected and the rate of the pump infusion
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized blinded parallel assignment

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: June 1, 2021
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share