ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618000244202

Ethics application status

Approved

Date submitted

21/09/2017

Date registered

15/02/2018

Date last updated

28/02/2024

Date data sharing statement initially provided

18/02/2019

Date results information initially provided

18/02/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Comparison of two different medications for treating low blood pressure after spinal anesthesia for cesarean section

Scientific title

Relative potency of noradrenaline versus phenylephrine in the prevention of hypotension after spinal anesthesia for cesarean section

Secondary ID [1]

'Nil known'

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Pregnancy

spinal anesthesia for cesarean delivery

Condition category

Condition code

Anaesthesiology

Other anaesthesiology

Reproductive Health and Childbirth

Childbirth and postnatal care

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The noradrenaline treatment is considered the intervention treatment.
All participating subjects will receive a standardized spinal anesthesia for cesarean delivery.
Vasopressor solutions will be freshly prepared at room temperature immediately before cesarean section by an investigator A, who apart from preparing the syringes, has no other role in the study. Only the investigator A will be aware of the content and dose of the syringe with vasopressor. In addition to the investigator A, there will be another investigator-observer responsible for data collection throughout the caesarean delivery who will also ensure strict adherence to the study protocol. Also, there will be one anesthetist responsible for clinical management of the patient only. Neither investigator-observer, nor the anesthetist responsible for clinical management of the patient will be aware of the content of the syringe with vasopressor. All syringes will be identical, and the infusions will be run at the same rate, as explained bellow.
Each patient will be allocated to one of two groups according to a computer-generated randomized code. Both vasopressors will be made up in 60ml syringes with normal saline 0.9% w/v. A Syramed®µSP6000 (Arcomed AG Medical Systems, Regensdorf, Switzerland) syringe driver infusion pump will be used at a fixed rate of 60ml/h. Only the investigator A preparing the syringes will be aware which one is noradrenaline or phenylephrine group.
The first patient will receive intravenously either phenylephrine 1200mcg in normal saline 0.9% w/v 60ml at 60ml/h infusion rate (20mcg/min) or noradrenaline 96mcg in normal saline 0.9% w/v 60ml at 60ml/h infusion rate (1.6mcg/min) according to randomization list generated from computer. The infusion will be started immediately after spinal anesthesia is administered.
A maximum of 3000mcg of phenylephrine can be diluted in normal saline 0.9% w/v 60ml (infusion rate 50mcg/min) and 240mcg of noradrenaline in normal saline 0.9% w/v 60ml (infusion rate 4mcg/min).
The investigator-observer blinded to the nature of the vasopressor infusion will assess the efficacy of each solution. The presence of hypotension, hypertension, tachycardia and bradycardia will be recorded until the delivery of the baby, or 30 min after intrathecal injection, whichever is earlier.
Hypotension is defined as a fall in systolic arterial pressure to <80% of baseline value. Hypertension is defined as an increase in systolic arterial pressure to >120% of baseline value. Tachycardia is defined as a rise in heart rate to >130 beats/min and bradycardia as a fall to <60 beats/min. The presence of hypotension, as defined above, during the study period means that the dose of infusion is classified as ineffective. It is classified as effective if the allocated drug regimen prevents hypotension during the study period. The dose of vasopressor for the subsequent patient will be determined by the efficacy of the dose in the previous patient, according to the technique of up–down sequential allocation. After an effective outcome, the next patient in respective group will receive a dose reduced by 150 mcg of phenylephrine or 12 mcg of noradrenaline. After an ineffective outcome, the dose for the next patient will be increased by the same amount, in the respective group.

Intervention code [1]

Prevention

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Phenylephrine group is the control group as currently phenylephrine is considered as the standard vasopressor for preventing hypotension after spinal anesthesia for cesarean delivery. This study is designed to derive the median effective dose of noradrenaline required to maintain the blood pressure during spinal anesthesia for cesarean delivery and to find out the relative potency of noradrenaline versus phenylephrine.

Control group

Active

Outcomes

Primary outcome [1]

1. Median effective dose (ED50) of noradrenaline and phenylephrine required to maintain the blood pressure during spinal anesthesia for cesarean delivery

2. To derive the median effective dose (ED50) of noradrenaline and phenylephrine we will be using the sequential allocation method. Up-down sequential allocation is a simple, robust and efficient method of identifying the median effective dose (ED50). The dose received by each of the subjects in the study is determined by the response of the previous subject. If the outcome is effective, the dose for the subsequent subject is decreased, while if ineffective it is increased. This approach derives the dose-response relationship and the ED50 is calculated using the Dixon and Massey formula

Timepoint [1]