Cesarean Section ComplicationsPhase 4INPEACENCT06248593
Continuous Infusion of Norepinephrine vs Phenylephrine During Spinal Anesthesia for Cesarean Section (INPEACE)
A Phase 4 study testing Continuous infusion of Norepinephrine and Continuous infusion of Phenylephrine in people with Cesarean Section Complications and Hypotension, run by Hassan II University at 2 sites in Morocco.
Trial summary
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: Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Cesarean Section Complications, Hypotension
- What is being tested?
- Continuous infusion of Norepinephrine and Continuous infusion of Phenylephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 2 sitesMorocco
- Study dates
- 29 Jan 2025to 15 Mar 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Full-term, singleton, pregnant women, nonlaboring.
- Scheduled for elective cesarean delivery under spinal anesthesia,
- American Society of Anesthesiologists physical status : 1 or 2
- Baseline systolic BP between 90 and 140 mm Hg.
Who cannot join
- Known fetal abnormality.
- Preexisting or pregnancy-induced hypertension, cardiovascular, cerebrovascular or kidney disease.
- Contraindication to spinal anesthesia.
- Peripartum hemorrhage.
- Body mass index above 40 kg/m2.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Morocco2 sites, 2 recruiting
- Not yet recruiting
University hospital Hassan II
Fes, 30060
Mohamed Adnane Berdai, MD-PhD, +212655260752, adnane.berdai@yahoo.fr
Mohamed Adnane Berdai, MD-PhD
- Recruiting
University hospital Hassan II
Fes, 30060
Mohamed Adnane Berdai, MD-PhD, +212655260752, adnane.berdai@yahoo.fr
About this study
Official title: Manually Controlled Continuous Infusion of Norepinephrine vs Phenylephrine During Spinal Anesthesia for Cesarean Section: A Double-blinded Randomized Controlled Study
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:
- Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective cesarean delivery have different effects on neonatal outcome ?
- Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective cesarean delivery have different effects on maternal hemodynamics? Participants will receive either phenylephrine or norepinephrine infusion, at the time of performing spinal anesthesia, the infusion rate will be adjusted manually depending on maternal arterial pressure.
Read the detailed description
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 :
- NE : 4 ml vial of norepinephrine bitartrate injection, 2 mg/ml.
- PHE : 10 ml Phenylephrine hydrochloride pre-filled syringe 50 μg/ml. In group PHE, The infusion is prepared by taking 1 mg of phenylephrine (2 prefilled syringe equals to 20 ml) and diluting it with 0.9% normal saline (NS) to attain a total volume of 40 mL and a concentration of 25 μg/mL.
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.
- Conditions
- Cesarean Section Complications, Hypotension
- Being tested
- Continuous infusion of Norepinephrine, Continuous infusion of Phenylephrine
- Keywords
- hypotension, norepinephrine, cesarean delivery, Obstetric anesthesia, Spinal anesthesia, Phenylephrine
- Medical subject headings
- Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous infusion of NorepinephrineDrug
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.
Continuous infusion of PhenylephrineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Phenylephrine | Active comparator | 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). Receives: Drug: Continuous infusion of Phenylephrine |
| Norepinephrine | Experimental | 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). Receives: Drug: Continuous infusion of Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Immediately after delivery
Secondary outcomes (20)
Umbilical artery base excess
From umbilical arterial blood gases.
Measured: Immediately after delivery
Umbilical artery partial pressure of oxygen
From umbilical arterial blood gases.
Measured: Immediately after delivery
Umbilical artery partial pressure of carbon dioxide
From umbilical arterial blood gases
Measured: 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.
Measured: 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.
Measured: 5 min after delivery
Number of newborns admitted to neonatal intensive care unit
Admission of the newborn to the neonatal intensive care unit
Measured: Within 24 hours after delivery
Blood glucose level from arterial umbilical cord blood gases
from arterial umbilical cord blood gases
Measured: 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
Measured: 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
Measured: from intrathecal injection to delivery of the fetus
Number of episodes of bradycardia before delivery
Heart rate less than 60 beats per minute
Measured: From intrathecal injection to delivery of the fetus.
Number of Hypertension episodes
Systolic blood pressure at or above 120% of baseline
Measured: In the intraoperative period.
Number of episodes of Tachycardia
Heart rate greater than 30% of baseline.
Measured: In the intraoperative period.
Number of episodes of nausea
episodes of nausea experienced by patients
Measured: From induction of spinal anesthesia to the end of the cesarean section.
Number of episodes of vomiting
Episodes of vomiting experienced by patients
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From induction of spinal anesthesia to the end of the cesarean section.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2024
- Study start29 Jan 2025
- Primary completion15 Mar 2026 (estimated)
- Study completion15 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Cesarean Section ComplicationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- It's a randomized, double-blind, two-arm, parallel, non-inferiority, controlled trial, which tha aim is to test the hypothesis that neonatal outcome, as assessed by umbilical artery pH, is at least as good (non-inferior) when prophylactic continuous manually controlled infusion of norepinephrine is used to maintain blood pressure during spinal anaesthesia for elective cesarean delivery compared with the same infusion modalities of phenylephrine with more stable blood pressure and less bradycardia.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hassan II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Adnane Berdai, Hassan II University
- Investigators
- Mohamed Adnane Berdai, MD-PhD, Principal investigator, University hospital Hassan II, Fes, Morocco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06248593
- Sponsor's protocol ID
- EC01/2024
- Acronym
- INPEACE
- Status last verified
- Sep 2025
- First submitted
- 31 Jan 2024
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected individual participant data will be shared and available to other researchers
Publications
Heesen M, Stewart A, Fernando R. Vasopressors for the treatment of maternal hypotension following spinal anaesthesia for elective caesarean section: past, present and future. Anaesthesia. 2015 Mar;70(3):252-7. doi: 10.1111/anae.13007. Epub 2015 Jan 13. No abstract available.
PubMed 25583307Doherty DG, Norris S, Madrigal-Estebas L, McEntee G, Traynor O, Hegarty JE, O'Farrelly C. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol. 1999 Aug 15;163(4):2314-21.
PubMed 10438977Hasanin A, Aiyad A, Elsakka A, Kamel A, Fouad R, Osman M, Mokhtar A, Refaat S, Hassabelnaby Y. Leg elevation decreases the incidence of post-spinal hypotension in cesarean section: a randomized controlled trial. BMC Anesthesiol. 2017 Apr 24;17(1):60. doi: 10.1186/s12871-017-0349-8.
PubMed 28438121Veeser M, Hofmann T, Roth R, Klohr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012 Aug;56(7):810-6. doi: 10.1111/j.1399-6576.2011.02646.x. Epub 2012 Feb 7.
PubMed 22313496Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg. 2010 Nov;111(5):1230-7. doi: 10.1213/ANE.0b013e3181f2eae1. Epub 2010 Sep 14.
PubMed 20841418Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015 Apr;122(4):736-45. doi: 10.1097/ALN.0000000000000601.
PubMed 25635593Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.
PubMed 28248702Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, Shapiro RE, Ranganathan P. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth. 2017 Feb;29:18-25. doi: 10.1016/j.ijoa.2016.08.005. Epub 2016 Aug 28.
PubMed 27720613Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic Norepinephrine Infusion for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery. Anesth Analg. 2018 Jun;126(6):1989-1994. doi: 10.1213/ANE.0000000000002243.
PubMed 28678073Belin O, Casteres C, Alouini S, Le Pape M, Dupont A, Boulain T. Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study. Anesth Analg. 2023 Mar 1;136(3):540-550. doi: 10.1213/ANE.0000000000006244. Epub 2022 Oct 24.
PubMed 36279409Ngan Kee WD. Phenylephrine infusions for maintaining blood pressure during spinal anesthesia for cesarean delivery: finding the shoe that fits. Anesth Analg. 2014 Mar;118(3):496-8. doi: 10.1213/ANE.0000000000000111. No abstract available.
PubMed 24557093Mohta M, Dubey M, Malhotra RK, Tyagi A. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth. 2019 May;38:25-31. doi: 10.1016/j.ijoa.2018.12.002. Epub 2018 Dec 13.
PubMed 30685301Ngan Kee WD. A Random-allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery. Anesthesiology. 2017 Dec;127(6):934-941. doi: 10.1097/ALN.0000000000001880.
PubMed 28872480
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Manually Controlled Continuous Infusion of Norepinephrine vs Phenylephrine During Spinal Anesthesia for Cesarean Section: A Double-blinded Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT06248593
- Acronym / sponsor ID
- INPEACE / EC01/2024
- Conditions
- Cesarean Section Complications, Hypotension
- Keywords
- hypotension, norepinephrine, cesarean delivery, Obstetric anesthesia, Spinal anesthesia, Phenylephrine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Hassan II UniversityUniversity, hospital or other
- Study start
- 29 Jan 2025 (actual)
- Primary completion
- 15 Mar 2026 (estimated)
- Study completion
- 15 Mar 2026 (estimated)
- First posted
- 8 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective cesarean delivery have different effects on neonatal outcome ?
- Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective cesarean delivery have different effects on maternal hemodynamics? Participants will receive either phenylephrine or norepinephrine infusion, at the time of performing spinal anesthesia, the infusion rate will be adjusted manually depending on maternal arterial pressure.
Detailed description
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 :
- NE : 4 ml vial of norepinephrine bitartrate injection, 2 mg/ml.
- PHE : 10 ml Phenylephrine hydrochloride pre-filled syringe 50 μg/ml. In group PHE, The infusion is prepared by taking 1 mg of phenylephrine (2 prefilled syringe equals to 20 ml) and diluting it with 0.9% normal saline (NS) to attain a total volume of 40 mL and a concentration of 25 μg/mL.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- It's a randomized, double-blind, two-arm, parallel, non-inferiority, controlled trial, which tha aim is to test the hypothesis that neonatal outcome, as assessed by umbilical artery pH, is at least as good (non-inferior) when prophylactic continuous manually controlled infusion of norepinephrine is used to maintain blood pressure during spinal anaesthesia for elective cesarean delivery compared with the same infusion modalities of phenylephrine with more stable blood pressure and less bradycardia.
| Arm | Type | Receives |
|---|---|---|
| Phenylephrine | Active comparator | Drug: Continuous infusion of PhenylephrineThe 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). |
| Norepinephrine | Experimental | Drug: Continuous infusion of NorepinephrineThe 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). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Full-term, singleton, pregnant women, nonlaboring.
- Scheduled for elective cesarean delivery under spinal anesthesia,
- American Society of Anesthesiologists physical status : 1 or 2
- Baseline systolic BP between 90 and 140 mm Hg.
Key exclusion criteria (5 listed)
- Known fetal abnormality.
- Preexisting or pregnancy-induced hypertension, cardiovascular, cerebrovascular or kidney disease.
- Contraindication to spinal anesthesia.
- Peripartum hemorrhage.
- Body mass index above 40 kg/m2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous infusion of NorepinephrineThe 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. | Drug | Norepinephrine |
| Continuous infusion of PhenylephrineThe 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. | Drug | Phenylephrine |
Primary outcome
Umbilical artery pH
Time frame: Immediately after delivery
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.
20 secondary outcomes
Umbilical artery base excess
Time frame: Immediately after delivery
Umbilical artery partial pressure of oxygen
Time frame: Immediately after delivery
Umbilical artery partial pressure of carbon dioxide
Time frame: Immediately after delivery
APGAR score
Time frame: 1 min after delivery
APGAR score
Time frame: 5 min after delivery
Number of newborns admitted to neonatal intensive care unit
Time frame: Within 24 hours after delivery
Blood glucose level from arterial umbilical cord blood gases
Time frame: Immediately after delivery
Number of hypotensive episodes
Time frame: from intrathecal injection to delivery of the fetus
Number of severe hypotensive episodes.
Time frame: from intrathecal injection to delivery of the fetus
Number of episodes of bradycardia before delivery
Time frame: From intrathecal injection to delivery of the fetus.
Number of Hypertension episodes
Time frame: In the intraoperative period.
Number of episodes of Tachycardia
Time frame: In the intraoperative period.
Number of episodes of nausea
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Number of episodes of vomiting
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.
Time frame: From induction of spinal anesthesia to the delivery of the fetus
Total dose of intraoperative study drug given.
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.
Time frame: from induction of spinal anesthesia to delivery of the fetus.
Total dose of intraoperative corrective boluses of ephedrine
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.
Time frame: from induction of spinal anesthesia to delivery of the fetus.
Total dose of Intraoperative corrective boluses of atropine
Time frame: From induction of spinal anesthesia to the end of the cesarean section.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Background: PubMed 25583307Heesen M, Stewart A, Fernando R. Vasopressors for the treatment of maternal hypotension following spinal anaesthesia for elective caesarean section: past, present and future. Anaesthesia. 2015 Mar;70(3):252-7. doi: 10.1111/anae.13007. Epub 2015 Jan 13. No abstract available.
- Background: PubMed 10438977Doherty DG, Norris S, Madrigal-Estebas L, McEntee G, Traynor O, Hegarty JE, O'Farrelly C. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol. 1999 Aug 15;163(4):2314-21.
- Background: PubMed 28438121Hasanin A, Aiyad A, Elsakka A, Kamel A, Fouad R, Osman M, Mokhtar A, Refaat S, Hassabelnaby Y. Leg elevation decreases the incidence of post-spinal hypotension in cesarean section: a randomized controlled trial. BMC Anesthesiol. 2017 Apr 24;17(1):60. doi: 10.1186/s12871-017-0349-8.
- Background: PubMed 22313496Veeser M, Hofmann T, Roth R, Klohr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012 Aug;56(7):810-6. doi: 10.1111/j.1399-6576.2011.02646.x. Epub 2012 Feb 7.
- Background: PubMed 20841418Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg. 2010 Nov;111(5):1230-7. doi: 10.1213/ANE.0b013e3181f2eae1. Epub 2010 Sep 14.
- Background: PubMed 25635593Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015 Apr;122(4):736-45. doi: 10.1097/ALN.0000000000000601.
- Background: PubMed 28248702Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.
- Background: PubMed 27720613Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, Shapiro RE, Ranganathan P. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth. 2017 Feb;29:18-25. doi: 10.1016/j.ijoa.2016.08.005. Epub 2016 Aug 28.
- Background: PubMed 28678073Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic Norepinephrine Infusion for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery. Anesth Analg. 2018 Jun;126(6):1989-1994. doi: 10.1213/ANE.0000000000002243.
- Background: PubMed 36279409Belin O, Casteres C, Alouini S, Le Pape M, Dupont A, Boulain T. Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study. Anesth Analg. 2023 Mar 1;136(3):540-550. doi: 10.1213/ANE.0000000000006244. Epub 2022 Oct 24.
- Background: PubMed 24557093Ngan Kee WD. Phenylephrine infusions for maintaining blood pressure during spinal anesthesia for cesarean delivery: finding the shoe that fits. Anesth Analg. 2014 Mar;118(3):496-8. doi: 10.1213/ANE.0000000000000111. No abstract available.
- Background: PubMed 30685301Mohta M, Dubey M, Malhotra RK, Tyagi A. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth. 2019 May;38:25-31. doi: 10.1016/j.ijoa.2018.12.002. Epub 2018 Dec 13.
- Individual participant dataSharing planned: Yes. All collected individual participant data will be shared and available to other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohamed Adnane Berdai, MD-PhD principal investigator
University hospital Hassan II, Fes, Morocco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continuous infusion of Norepinephrine and Continuous infusion of Phenylephrine in people with Cesarean Section Complications and Hypotension, run by Hassan II University at 2 sites in Morocco.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Morocco. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamed Adnane Berdai, MD-PhD (+212655260752, adnane.berdai@yahoo.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Umbilical artery pH (time frame: Immediately after delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06248593, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.