A Phase 4 interventional study of Continuous infusion of Norepinephrine and Continuous infusion of Phenylephrine in Cesarean Section Complications and Hypotension, sponsored by Hassan II University. Recruiting at 2 sites in Morocco. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-09-09.
Sponsored by Hassan II University · Phase 4, Interventional, and Treatment
The goal of this clinical trial is to compare norepinephrine and ephedrine in maintaining blood pressure during spinal anaesthesia for elective cesarean delivery. The main questions it aims to answer are:
It's a randomized, double-blind, two-arm, parallel, non-inferiority, controlled trial that will be conducted in Hassan II University Hospital, Fes, Morocco. The aim of this study is to test the hypothesis that neonatal outcome, as assessed by potential of hydrogen (pH) of umbilical artery, is at least as good (non-inferior) when prophylactic continuous manually controlled infusion of norepinephrine (NE) is used to maintain blood pressure during spinal anaesthesia for elective cesarean delivery compared with the same infusion modalities of phenylephrine (PHE) with more stable blood pressure and less bradycardia.
Before starting the study, a simple randomization sequence will generate codes for two equal-sized groups. One code for each patient will be placed into a sealed, opaque, sequentially numbered envelope by a research assistant, who is not involved in patient management or data collection.
Another person not involved in subsequent patient care or assessement either, will open the envelope for each patient shortly before commencement of the study and prepared two identical 50-mL syringes according to the code contained in the envelops, patients will be randomly allocated to receive PHE or NE infusion. All the syringes were labelled as "study drug", To standardize and study the effects without affecting the potency of the drugs, vasopressor doses were taken in an equipotent ratio (12.5:1) for PHE:NE based on previous studies.
The medication used in this study are :
In group NE, Norepinephrine infusion will be prepared by taking one vial (8 mg) of norepinephrine, and diluting it with 496 ml of 0.9% normal saline (NS) to attain a concentration of NE of 16 µg/ml. 10 ml of this solution Will be diluted in 0.9% NS to reach a total volume of 40 mL and a concentration of 4 μg/mL of NE which correspond to 2 µg/ml of norepinephrine base.
Eleven milligrams of hyperbaric bupivacaine in addition to 20 μg fentanyl will be injected in the L2-L3, L3-L4 or L4-L5 intervertebral space using a 25-gauge pencil-point spinal needle in the sitting position. Block success will be assessed by sensory blockade level using pinprick test and surgery would not begin unless the sensory block reached T6 level. Patients with inadequate sensory blockade would receive general anesthesia for cesarean delivery, and will be excluded from the study.
Simultaneously with the intrathecal injection, rapid intravenous vascular volume expansion by 1000ml NS solution will be started, with a pressure infuser bag inflated.
The infusion will be initiated at a rate of 96 mL/hour (1.6 mL/minute), that correspond to a phenylephrine rate infusion of 40 μg/minute or norepinephrine rate infusion of 6.4 μg/minute. Both vasopressor infusions will be started at the same time that cerebrospinal fluid is obtained before the injection of the local anesthetic into the cerebrospinal fluid. and then manually adjusted within the range 0-144 mL/h : PHE (0-60 μg/min), NE (0-9.6 µg/min), according to values of systolic blood pressure (SBP) measured noninvasively and recorded at 1-minute intervals along the intraoperative period, with the objective of maintaining values near baseline, according to this modalities (table 1). Heart rate (HR) will be monitored continuously and recorded at 1-min interval.
SBP (% of baseline) Infusion rate (ml/min)) NE delivery rate (µg/min) PHE delivery rate (µg/min) >120% or >140 mmhg 0 0 0 100-120% 48 3.2 20 90-100% 96 6.4 40 80-90% 120 8 50 \<80% 144 9.6 60
Table : Algorithm of manually controlled infusion rate and its corresponding amount of study drug (norepinephrine or phenylephrine depending on randomisation)
A researcher in the theater will manage the infusions and collect the data for analysis. Episodes of hypotension, hypertension, bradycardia and tachycardia will be recorded.
Intraoperative hypertension (defined as SBP greater than 120% of the baseline or > 140 mmhg) will be managed by stopping temporarily drug infusion. The infusion is resumed when blood pressure return to \< 120% of the SBP baseline).
Postspinal hypotension (defined as decreased SBP less than 80% of the baseline or SBP\< 90 mmhg reading during the period from intrathecal injection to delivery of the fetus) will be managed by increasing vasopressor infusion dose according to study protocol infusion above. In case of persistant postspinal hypotension despite increasing vasopressor doses, it's will be managed by 2-ml bolus of the infusion which correspond for parturients with NE infusion to 8µg and those with PHE to 50 μg. Additional vasopressor bolus will be given if SBP did not respond to the first dose within 2 min despite continuing the infusion.
In case of persistence of hypotension, A rescue bolus of at least ephedrine 6 mg is recommended, and repeated according to the severity and persistence of the hypotension.
After delivery and in the absence of hemorrhage, the vasopressor flow rate will be reduced in steps of 20 mL∙h-1, while maintaining an SBP >80% of baseline, a minimum delay of 5 minutes between 2 flow reductions is recommended to avoid secondary hypotension.
Intraoperative bradycardia (defined as heart rate less than 60 beats per minute without hypotension will be managed by stopping the vasopressor infusion.
If bradycardia is associated with hypotension, the patient will be managed by IV ephedrine 9 mg. If bradycardia persist or decrease below 50 beats/min after the previous measures, an IV atropine bolus (0.5 mg) should be given.
Umbilical arterial blood (UA) will be sampled from a double-clamped segment of umbilical cord by using arterial blood gas syringes. Within 20 min after clamping, umbilical blood gas will be analyzed with a bedside Blood gas Analyzer System.
885 studies on the registry are indexed under Hypotension; 195 are open to participants now.
This study's planned enrollment of 140 is above the median of 87 across 590 interventional studies indexed under Hypotension.
Browse Hypotension studies →Hassan II University is the lead sponsor of 4 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The infusion will have a concentration of Phenylephrine of 25 μg/mL and will be initiated at a rate of 96 mL/hour (1.6 mL/minute), that correspond to a phenylephrine rate infusion of 40 μg/min, then the infusion rate will be manually adjusted within the range 0-144 mL/h : PHE (0-60 μg/min).
Drug: Continuous infusion of Phenylephrine
The infusion will have a concentration of Norepinephrine of 4 μg/mL and will be initiated at a rate of 96 mL/hour (1.6 mL/minute), that correspond to norepinephrine rate infusion of 6.4 μg/min, then the infusion rate will be manually adjusted within the range 0-144 mL/h : Norepinephrine (0-9.6 µg/min).
Drug: Continuous infusion of Norepinephrine
The rate of norepinephrine infusion will be adjusted according to values of systolic blood pressure measured noninvasively and recorded at 1-minute intervals along the intraoperative period, with the objective of maintaining values near baseline.
The rate of phenylephrine infusion will be adjusted according to values of systolic blood pressure measured noninvasively and recorded at 1-minute intervals along the intraoperative period, with the objective of maintaining values near baseline.
Umbilical artery pH
Umbilical arterial blood (UA) will be sampled from a double-clamped segment of umbilical cord by using arterial blood gas syringes.Umbilical blood gas will be analyzed with a bedside Blood gas Analyzer System.
Time frame: Immediately after delivery
Umbilical artery base excess
From umbilical arterial blood gases.
Time frame: Immediately after delivery
Umbilical artery partial pressure of oxygen
From umbilical arterial blood gases.
Time frame: Immediately after delivery
Umbilical artery partial pressure of carbon dioxide
From umbilical arterial blood gases
Time frame: Immediately after delivery
APGAR score
A= Appearance P=Pulse G=Grimace A=Attitude R=Respiration. Values of APGAR score vary from 0 to 10, higher scores mean a better outcome.
Time frame: 1 min after delivery
APGAR score
A= Appearance P=Pulse G=Grimace A=Attitude R=Respiration. Values of APGAR score vary from 0 to 10, higher scores mean a better outcome.
Time frame: 5 min after delivery
Number of newborns admitted to neonatal intensive care unit
Admission of the newborn to the neonatal intensive care unit
Time frame: Within 24 hours after delivery
Blood glucose level from arterial umbilical cord blood gases
from arterial umbilical cord blood gases
Time frame: Immediately after delivery
Number of hypotensive episodes
Defined as decreased systolic blood pressure intraoperatively less than 80% of the baseline or less than 90 mmhg
Time frame: from intrathecal injection to delivery of the fetus
Number of severe hypotensive episodes.
Defined as decreased systolic blood pressure intraoperatively less than 60% of the baseline or less than 70 mmhg
Time frame: from intrathecal injection to delivery of the fetus
Number of episodes of bradycardia before delivery
Heart rate less than 60 beats per minute
Time frame: From intrathecal injection to delivery of the fetus.
Number of Hypertension episodes
Systolic blood pressure at or above 120% of baseline
Time frame: In the intraoperative period.
Number of episodes of Tachycardia
Heart rate greater than 30% of baseline.
Time frame: In the intraoperative period.
Number of episodes of nausea
episodes of nausea experienced by patients
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Number of episodes of vomiting
Episodes of vomiting experienced by patients
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Total dose of study drug given until delivery of the fetus.
The total dose given of norepinephrine or phenylephrine depending on randomization
Time frame: From induction of spinal anesthesia to the delivery of the fetus
Total dose of intraoperative study drug given.
The total dose given of norepinephrine or phenylephrine depending on randomization
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Total dose of ephedrine from induction of spinal anesthesia to delivery of the fetus.
Total dose of corrective boluses of ephedrine as a rescue drug
Time frame: from induction of spinal anesthesia to delivery of the fetus.
Total dose of intraoperative corrective boluses of ephedrine
Total dose of corrective boluses of ephedrine as a rescue drug
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Total dose of corrective boluses of atropine from induction of spinal anesthesia to delivery of the fetus.
Total dose of corrective boluses of atropine in case of bradycardia
Time frame: from induction of spinal anesthesia to delivery of the fetus.
Total dose of Intraoperative corrective boluses of atropine
Total dose of corrective boluses of atropine in case of bradycardia
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Plan to share: Yes — All collected individual participant data will be shared and available to other researchers
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: the IPD and any additional supporting information will become available, 3 months after publication and will be available for a period of 6 months.
Access criteria: Undecided now
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