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Prevention of Hypotension During Cesarean Section (NOR-PHEN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03842046
Recruitment Status : Completed
First Posted : February 15, 2019
Last Update Posted : May 26, 2020
Sponsor:
Collaborator:
Alexandra Hospital, Athens, Greece
Information provided by (Responsible Party):
Dr Kassiani Theodoraki, Aretaieion University Hospital

Brief 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

Condition or disease Intervention/treatment Phase
Hypotension Symptomatic Obstetric Anesthesia Problems Cesarean Section Complications Vasoconstriction Procedure: phenylephrine infusion Procedure: norepinephrine infusion Not Applicable

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Comparison of Continuous Infusion of Noradrenaline Versus Phenylephrine During Cesarean Section Under Spinal Anesthesia. A Randomized Controlled Trial
Actual Study Start Date : February 16, 2019
Actual Primary Completion Date : August 31, 2019
Actual Study Completion Date : August 31, 2019


Arm Intervention/treatment
Active Comparator: phenylephrine infusion
phenylephrine infusion (30 mL/h corresponding to 50 μg/min)
Procedure: phenylephrine infusion
In parturients allocated to the phenylephrine group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

Active Comparator: norepinephrine infusion
norepinephrine infusion (30 mL/h corresponding to 4 μg/min)
Procedure: norepinephrine infusion
In parturients allocated to the norepinephrine group group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established




Primary Outcome Measures :
  1. incidence of bradycardia [ Time Frame: intraoperative ]
    any incidence of heart rate<60/min will be recorded


Secondary Outcome Measures :
  1. need for vasoconstrictor [ Time Frame: intraoperative ]
    parturient needed or not vasoconstrictor during the operation

  2. type of vasoconstrictor administered [ Time Frame: intraoperative ]
    phenylephrine verus ephedrine

  3. number of bolus doses of vasoconstrictor administered [ Time Frame: intraoperative ]
    number of provided interventions to maintain systolic blood pressure within the set limits will be recorded

  4. total dose of vasoconstrictor administered [ Time Frame: intraoperative ]
    total dose in mg for ephedrine or μg for phenylephrine

  5. incidence of hypotension [ Time Frame: intraoperative ]
    any occurrence of hypotension throughout the operation will be recorded (systolic arterial pressure<80% of baseline throughout the operation)

  6. incidence of hypertension [ Time Frame: intraoperative ]
    any incidence of systolic blood pressure >120% of baseline will be recorded

  7. incidence of nausea/vomiting [ Time Frame: intraoperative ]
    incidence of nausea and vomiting throughout the operation

  8. neonatal Apgar score at 1 min [ Time Frame: 1 min post delivery ]
    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.

  9. neonatal Apgar score at 5 min [ Time Frame: 5 min post delivery ]
    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.

  10. neonatal blood gases [ Time Frame: 1 min post delivery ]
    fetal cord blood analysis will be performed immediately post-delivery

  11. glucose in neonatal blood [ Time Frame: 1 min post delivery ]
    glucose will be measured in the cord blood gas sample taken immediately post-delivery



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Ages Eligible for Study:   18 Years to 48 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Body Mass Index (BMI) >40 kg/m2
  • Body weight <50 kg
  • Body weight>100 kg
  • height<150 cm
  • height>180 cm
  • multiple gestation
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03842046


Locations
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Greece
Aretaieion University Hospital
Athens, Greece, 115 28
Alexandra General Hospital of Athens
Athens, Greece, 11528
Sponsors and Collaborators
Aretaieion University Hospital
Alexandra Hospital, Athens, Greece
Investigators
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Principal Investigator: Kassiani Theodoraki, PhD Aretaieion University Hospital
Principal Investigator: Emmanouil Stamatakis, PhD Alexandra General Hospital of Athens
Principal Investigator: Dimitrios Valsamidis, PhD Alexandra General Hospital of Athens
Principal Investigator: Sofia Chatzilia, PhD Alexandra General Hospital of Athens
Publications:

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Responsible Party: Dr Kassiani Theodoraki, Associate Professor of Anesthesiology, Aretaieion University Hospital
ClinicalTrials.gov Identifier: NCT03842046    
Other Study ID Numbers: NOR-PHEN
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: May 26, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr Kassiani Theodoraki, Aretaieion University Hospital:
hypotension
phenylephrine
noradrenaline
cardiac output
fetal
maternal hemodynamics
cesarean section
Additional relevant MeSH terms:
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Hypotension
Vascular Diseases
Cardiovascular Diseases
Phenylephrine
Oxymetazoline
Norepinephrine
Cardiotonic Agents
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sympathomimetics
Vasoconstrictor Agents
Nasal Decongestants
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents