AzTrials
AzTrials

Hypotension SymptomaticNOR-PHENNCT03842046

Prevention of Hypotension During Cesarean Section

A study testing phenylephrine infusion and norepinephrine infusion in people with Hypotension Symptomatic and Obstetric Anesthesia Problems, run by Aretaieion University Hospital at 2 sites in Greece.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The aim of this double-blind randomized study will be to compare a fixed-rate prophylactic noradrenaline infusion to a fixed-rate prophylactic phenylephrine infusion during elective cesarean section under combined spinal-epidural anesthesia Read more about this study

Who is it for?
Ages 18 to 48 years, women only
What is being tested?
phenylephrine infusion and norepinephrine infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
2 sitesGreece
Study dates
16 Feb 2019to 31 Aug 2019
Phase
Interventional
Are there results?
None posted in the registry

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 48 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • adult parturients, American Society of Anesthesiologists (ASA) I-II, singleton gestation>37 weeks
  • elective cesarean section

Who cannot join

  • Body Mass Index (BMI) >40 kg/m2
  • Body weight <50 kg
  • Body weight>100 kg
  • height<150 cm
  • height>180 cm
  • multiple gestation
Show all 17Show fewer
  • fetal abnormality
  • fetal distress
  • active labor
  • cardiac disease
  • pregnancy-induced hypertension
  • thrombocytopenia
  • coagulation abnormalities
  • use of antihypertensive medication during pregnancy
  • communication or language barriers
  • lack of informed consent
  • contraindication for regional anesthesia

Trial locations and contacts

2 sites in 1 country.

Greece2 sites
  • Aretaieion University Hospital

    Athens, 115 28

  • Alexandra General Hospital of Athens

    Athens, 11528

Other trials in Greece

About this study

Official title: Comparison of Continuous Infusion of Noradrenaline Versus Phenylephrine During Cesarean Section Under Spinal Anesthesia. A Randomized Controlled Trial

The aim of this double-blind randomized study will be to compare a fixed-rate prophylactic noradrenaline infusion to a fixed-rate prophylactic phenylephrine infusion during elective cesarean section under combined spinal-epidural anesthesia

Read the detailed description
  • Spinal anesthesia is the anesthetic technique of choice for elective cesarean section.
  • Spinal anesthesia can be complicated by hypotension, with incidence exceeding 80% occasionally. Hypotension can lead to nausea, emesis and a subjective feeling of discomfort due to cerebral hypoperfusion. If left untreated, severe or sustained hypotension can lead to decreased uteroplacental flow and fetal distress of premature or compromised fetuses while severe complications to the parturient might ensue, such as loss of consciousness, aspiration, apnea or cardiac arrest
  • One of the standard techniques to avoid maternal hypotension is the administration of a continuous phenylephrine infusion while studies have demonstrated its superiority as compared to rescue bolus phenylephrine administration. Additionally, as compared to ephedrine, phenylephrine is associated with less neonatal acidosis and better maintenance of uteroplacental blood flow. However, phenylephrine can lead to baroreceptor-mediated reflex bradycardia, with untoward consequences for maternal cardiac output.
  • Recently, noradrenaline has been shown to be effective in maintaining blood pressure in obstetric patients. Noradrenaline is a strong-alpha agonist with weak beta-action, too. Therefore, it might prove superior in maintaining cardiac output as compared to phenylephrine. There have been a few studies examining the use of noradrenaline as a continuous infusion in this context but the optimal dose and safety and efficacy profile of noradrenaline continuous infusion in obstetrics is yet to be determined
  • In all parturients, standard hemodynamic monitoring will be applied. Baseline systolic arterial pressure will be considered the average of three consecutive measurements that will not differ more than 10% among them. All parturients will have a peripheral intravenous catheter placed in the upper extremity after baseline hemodynamic measurements are recorded and will be infused 5 mL/kg of hydroxyethylstarch (pre-loading) before the regional procedure.
  • Study group allocation will taker place according to a computer-generated sequence of random numbers. A standard spinal anesthetic consisting of ropivacaine 0.75% 1.8 mL plus fentanyl 10 μg will be administered in the left lateraL position at the L3-4 or L4-5 vertebral interspace. The study infusion medication (either phenylephrine or norepinephrine, depending on group allocation) will be started at the same time cerebrospinal fluid is obtained, immediately before injection of spinal medications. After the intrathecal injection, patients will placed in the supine position with a left lateral tilt of the table to provide left uterine displacement and to prevent aortocaval compression. The spinal sensory level will be tested bilaterally by pinprick to ensure a T4 dermatomal level before surgical incision.
  • Hemodynamic parameters (systolic arterial blood pressure, diastolic arterial blood pressure, mean arterial blood pressure and heart rate) will be measured and recorded at discrete timepoints throughout the operation (baseline, start of vasoactive agent administration, parturient at supine position, sympathetic block at T4, knife-to-skin, neonatal delivery, start of oxytocin administration, start of skin closure, end of operation.
  • During the operation, a rescue dose of phenylephrine 50 μg will be administered when systolic arterial pressure drops below 80% of baseline in combination with heart rate>80 bpm. Ephedrine 5 mg will be administered when there is hypotension (systolic arterial pressure <80% of baseline) in combination with heart rate less than 80 bpm. Hypertensive episodes (systolic blood pressure >120% of baseline) will be treated with halving the infusion while when systolic arterial pressure increases above 130% of baseline the infusion will be discontinued and will be restarted when systolic blood pressure decreases below the upper limit of the target range (120% of baseline value).
Being tested
phenylephrine infusion, norepinephrine infusion
Keywords
hypotension, phenylephrine, noradrenaline, cardiac output, fetal, maternal hemodynamics, cesarean section
Medical subject headings
Hypotension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • phenylephrine infusionProcedure or surgery

    In parturients allocated to the phenylephrine group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

  • norepinephrine infusionProcedure or surgery

    In parturients allocated to the norepinephrine group group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

Study groups in NCT03842046
Study groupRoleWhat they receive
phenylephrine infusionActive comparatorphenylephrine infusion (30 mL/h corresponding to 50 μg/min)
Receives: Procedure: phenylephrine infusion
norepinephrine infusionActive comparatornorepinephrine infusion (30 mL/h corresponding to 4 μg/min)
Receives: Procedure: norepinephrine infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. incidence of bradycardia

    any incidence of heart rate<60/min will be recorded

    Measured: intraoperative

Secondary outcomes (11)
  1. need for vasoconstrictor

    parturient needed or not vasoconstrictor during the operation

    Measured: intraoperative

  2. type of vasoconstrictor administered

    phenylephrine verus ephedrine

    Measured: intraoperative

  3. number of bolus doses of vasoconstrictor administered

    number of provided interventions to maintain systolic blood pressure within the set limits will be recorded

    Measured: intraoperative

  4. total dose of vasoconstrictor administered

    total dose in mg for ephedrine or μg for phenylephrine

    Measured: intraoperative

  5. incidence of hypotension

    any occurrence of hypotension throughout the operation will be recorded (systolic arterial pressure<80% of baseline throughout the operation)

    Measured: intraoperative

  6. incidence of hypertension

    any incidence of systolic blood pressure >120% of baseline will be recorded

    Measured: intraoperative

  7. incidence of nausea/vomiting

    incidence of nausea and vomiting throughout the operation

    Measured: intraoperative

  8. neonatal Apgar score at 1 min

    neonatal Apgar score will be recorded at 1 min after delivery. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Scores 7 and above are generally normal; 4 to 6, fairly low; and 3 and below are generally regarded as critically low and cause for immediate resuscitative efforts.

    Measured: 1 min post delivery

  9. neonatal Apgar score at 5 min

    neonatal Apgar score will be recorded at 5 min after delivery. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Scores 7 and above are generally normal; 4 to 6, fairly low; and 3 and below are generally regarded as critically low and cause for immediate resuscitative efforts.

    Measured: 5 min post delivery

  10. neonatal blood gases

    fetal cord blood analysis will be performed immediately post-delivery

    Measured: 1 min post delivery

  11. glucose in neonatal blood

    glucose will be measured in the cord blood gas sample taken immediately post-delivery

    Measured: 1 min post delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2019
  2. Study start16 Feb 2019
  3. Primary completion31 Aug 2019
  4. Study completion31 Aug 2019

Resources

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 N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03842046
Sponsor's protocol ID
NOR-PHEN
Acronym
NOR-PHEN
Status last verified
May 2020
First submitted
13 Feb 2019
Last updated
26 May 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Afolabi BB, Lesi FE. Regional versus general anaesthesia for caesarean section. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD004350. doi: 10.1002/14651858.CD004350.pub3.

    PubMed 23076903
  • Klohr S, Roth R, Hofmann T, Rossaint R, Heesen M. Definitions of hypotension after spinal anaesthesia for caesarean section: literature search and application to parturients. Acta Anaesthesiol Scand. 2010 Sep;54(8):909-21. doi: 10.1111/j.1399-6576.2010.02239.x. Epub 2010 Apr 23.

    PubMed 20455872
  • Maayan-Metzger A, Schushan-Eisen I, Todris L, Etchin A, Kuint J. Maternal hypotension during elective cesarean section and short-term neonatal outcome. Am J Obstet Gynecol. 2010 Jan;202(1):56.e1-5. doi: 10.1016/j.ajog.2009.07.012. Epub 2009 Aug 28.

    PubMed 19716536
  • Ngan Kee WD. Prevention of maternal hypotension after regional anaesthesia for caesarean section. Curr Opin Anaesthesiol. 2010 Jun;23(3):304-9. doi: 10.1097/ACO.0b013e328337ffc6.

    PubMed 20173633
  • Laudenbach V, Mercier FJ, Roze JC, Larroque B, Ancel PY, Kaminski M, Breart G, Diemunsch P, Subtil D, Lejus C, Fresson J, Arnaud C, Rachet B, Burguet A, Cambonie G; Epipage Study Group. Anaesthesia mode for caesarean section and mortality in very preterm infants: an epidemiologic study in the EPIPAGE cohort. Int J Obstet Anesth. 2009 Apr;18(2):142-9. doi: 10.1016/j.ijoa.2008.11.005. Epub 2009 Feb 4.

    PubMed 19195873
  • Ngan Kee WD, Khaw KS, Ng FF, Lee BB. Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2004 Mar;98(3):815-21, table of contents. doi: 10.1213/01.ane.0000099782.78002.30.

    PubMed 14980943
  • Ngan Kee WD, Khaw KS, Ng FF. Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section. Br J Anaesth. 2004 Apr;92(4):469-74. doi: 10.1093/bja/aeh088. Epub 2004 Feb 20.

    PubMed 14977792
  • Siddik-Sayyid SM, Taha SK, Kanazi GE, Aouad MT. A randomized controlled trial of variable rate phenylephrine infusion with rescue phenylephrine boluses versus rescue boluses alone on physician interventions during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2014 Mar;118(3):611-8. doi: 10.1213/01.ane.0000437731.60260.ce.

    PubMed 24299932
  • Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2002 Apr;94(4):920-6, table of contents. doi: 10.1097/00000539-200204000-00028.

    PubMed 11916798
  • Ngan Kee WD, Khaw KS, Lau TK, Ng FF, Chui K, Ng KL. Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective Caesarean section*. Anaesthesia. 2008 Dec;63(12):1319-26. doi: 10.1111/j.1365-2044.2008.05635.x.

    PubMed 19032300
  • Cooper DW, Carpenter M, Mowbray P, Desira WR, Ryall DM, Kokri MS. Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2002 Dec;97(6):1582-90. doi: 10.1097/00000542-200212000-00034.

    PubMed 12459688
  • Stewart 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 20841418
  • Ngan 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 25635593
  • Vallejo 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 27720613
  • Carvalho B, Dyer RA. Norepinephrine for Spinal Hypotension during Cesarean Delivery: Another Paradigm Shift? Anesthesiology. 2015 Apr;122(4):728-30. doi: 10.1097/ALN.0000000000000602. No abstract available.

    PubMed 25654435

Questions about this trial

What is this clinical trial studying?

A study testing phenylephrine infusion and norepinephrine infusion in people with Hypotension Symptomatic and Obstetric Anesthesia Problems, run by Aretaieion University Hospital at 2 sites in Greece.

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 2 inclusion and 17 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: finished, as of the sponsor's last update on 26 May 2020. 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 Greece. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

incidence of bradycardia (time frame: intraoperative). 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 NCT03842046, which also lists 15 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 26 May 2020.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in