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出境医 / 临床实验 / Prophylactic Phenylephrine Co-administration During Caesarean Section

Prophylactic Phenylephrine Co-administration During Caesarean Section

Study Description
Brief Summary:
This single centre prospective alternating intervention study will aim to compare prophylactic phenylephrine given in the first litre of Ringers lactate as co-load in healthy patients having an elective caesarean section under spinal anaesthesia at Edendale Hospital to the existing national protocol guideline - for the treatment of obstetric spinal hypotension.

Condition or disease Intervention/treatment Phase
Cesarean Section Complications Anesthesia Complication Drug: Phenylephrine Not Applicable

Detailed Description:

Spinal anaesthesia is currently standard of care for patients undergoing caesarean section. Obstetric spinal hypotension is a common and important problem, related to important maternal and foetal outcomes. The prevention and treatment of spinal hypotension has been well researched in resource-rich settings, a context different from that encountered in the South African setting. It has been previously shown that a prophylactic phenylephrine infusion is effective in resource-limited settings, but this method is still dependent on the availability of an infusion pump.The ideal dose offering the best risk to benefit profile is 25 to 50 mcg/min. It has recently been shown that a prophylactic phenylephrine infusion, administered by an infusion pump, appears safe and effective in resource-constrained environments. However, some institutions in South Africa are limited by a lack of available infusion pumps. There is an urgent need to translate these research findings into a pragmatic management strategy that is safe and effective where this equipment is lacking. A 18g Jelco allows flow of approximately 100 ml/min in the absence of a pressure bag: therefore with 500 mcg in 1000 ml of ringers lactate and a fully opened line, a maximum dose of 50 mcg.min-1 will be achieved. If the rate is 50 ml/min (20 minutes for the first litre) the dose will be 25 mcg.min-1. This dose range will offer maximum benefit with low risk of side effects.

This exploratory study will establish if a phenylephrine (500 mcg) bolus, added to the first litre of Ringers lactate given as a co-load, is an effective and safe means to prevent post obstetric spinal hypotension. This regime will be compared to the existing South African national protocol of the management of obstetric spinal hypotension. The findings of this study will provide valuable information regarding a safe and potentially effective means to prevent obstetric spinal hypotension.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single centre prospective alternating intervention study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prophylactic Phenylephrine and Fluid Co-administration to Reduce Spinal Hypotension During Elective Caesarean Section in a Resource-limited Setting: a Prospective Alternating Intervention Study
Actual Study Start Date : May 1, 2018
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018
Arms and Interventions
Arm Intervention/treatment
No Intervention: Bolus group
Hypotension occurring under spinal anaesthesia (SBP < 90mmHg) requires pharmacological treatment. The pharmacological management of hypotension, once diagnosed, will be the same regardless of the protocol being used. If the heart rate is greater than 70 beats per minute, phenylephrine will be administered in a dose of 50-100 mcg as an intravenous bolus. If the heart rate is less than 70 beats per minute, ephedrine will be administered in a dose of 5-10 mg. The dose within this range will be decided by the attending anaesthetist. In both arms, Ringers Lactate fluid should run fast if hypotension occurs.
Active Comparator: Phenylephrine coload group
Phenylephrine 500ug will be added to the first litre of ringer's lactate infused on initiation of spinal anaesthesia. If the phenylephrine infusion protocol is being used, and the mean arterial pressure (MAP) rises to greater than 20% of the initial MAP, and where this rise in MAP is not due to a recent bolus of either phenylephrine or ephedrine (within 2 minutes), the Ringers Lactate infusion will be switched off. The pharmacological management of hypotension, once diagnosed, will be the same regardless of the protocol being used. If the heart rate is greater than 70 beats per minute, phenylephrine will be administered in a dose of 50-100 mcg as an intravenous bolus. If the heart rate is less than 70 beats per minute, ephedrine will be administered in a dose of 5-10 mg. In both arms, Ringers Lactate fluid should run fast if hypotension occurs.
Drug: Phenylephrine
Prophylactic phenylephrine infusion as part of fluid coload
Other Name: Phenylephrine coload

Outcome Measures
Primary Outcome Measures :
  1. Post spinal hypotension [ Time Frame: from insertion of spinal anaesthesia until the delivery of the baby ]
    The incidence of post spinal hypotension (SBP <90 mmHg)


Secondary Outcome Measures :
  1. Maternal symptoms [ Time Frame: time of spinal insertion till delivery of the baby ]
    nausea, vomiting, headache and dizziness.

  2. Maternal cardiac arrest [ Time Frame: time of spinal insertion till delivery of the baby ]
    Requirement for cardiopulmonary resuscitation

  3. Maternal bradycardia [ Time Frame: time of spinal insertion till delivery of the baby ]
    maternal bradycardia requiring atropine administration

  4. Requirement for vasopressor [ Time Frame: time of spinal insertion till delivery of the baby ]
    Number of vasopressor boluses

  5. Highest blood pressure [ Time Frame: time of spinal insertion till delivery of the baby ]
    Highest systolic blood pressure (mmHg)

  6. Lowest blood pressure [ Time Frame: time of spinal insertion till delivery of the baby ]
    Lowest systolic blood pressure (mmHg)

  7. Lowest maternal heart rate [ Time Frame: time of spinal insertion till delivery of the baby ]
    Lowest heart rate (beats per minute)


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All ASA 1-2 patients undergoing elective caesarean

Exclusion Criteria:

  • ASA grade >2 Hypertensive disease in pregnancy Dysrhythmia Failed spinal requiring conversion to a general anaesthetic
Contacts and Locations

Locations
Layout table for location information
South Africa
Edendale Hospital
Pietermaritzburg, KwaZulu-Natal, South Africa, 3201
Sponsors and Collaborators
University of KwaZulu
Investigators
Layout table for investigator information
Principal Investigator: David G Bishop, PhD University of KwaZulu
Tracking Information
First Submitted Date  ICMJE June 19, 2019
First Posted Date  ICMJE July 2, 2019
Last Update Posted Date July 2, 2019
Actual Study Start Date  ICMJE May 1, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2019)
Post spinal hypotension [ Time Frame: from insertion of spinal anaesthesia until the delivery of the baby ]
The incidence of post spinal hypotension (SBP <90 mmHg)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2019)
  • Maternal symptoms [ Time Frame: time of spinal insertion till delivery of the baby ]
    nausea, vomiting, headache and dizziness.
  • Maternal cardiac arrest [ Time Frame: time of spinal insertion till delivery of the baby ]
    Requirement for cardiopulmonary resuscitation
  • Maternal bradycardia [ Time Frame: time of spinal insertion till delivery of the baby ]
    maternal bradycardia requiring atropine administration
  • Requirement for vasopressor [ Time Frame: time of spinal insertion till delivery of the baby ]
    Number of vasopressor boluses
  • Highest blood pressure [ Time Frame: time of spinal insertion till delivery of the baby ]
    Highest systolic blood pressure (mmHg)
  • Lowest blood pressure [ Time Frame: time of spinal insertion till delivery of the baby ]
    Lowest systolic blood pressure (mmHg)
  • Lowest maternal heart rate [ Time Frame: time of spinal insertion till delivery of the baby ]
    Lowest heart rate (beats per minute)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prophylactic Phenylephrine Co-administration During Caesarean Section
Official Title  ICMJE Prophylactic Phenylephrine and Fluid Co-administration to Reduce Spinal Hypotension During Elective Caesarean Section in a Resource-limited Setting: a Prospective Alternating Intervention Study
Brief Summary This single centre prospective alternating intervention study will aim to compare prophylactic phenylephrine given in the first litre of Ringers lactate as co-load in healthy patients having an elective caesarean section under spinal anaesthesia at Edendale Hospital to the existing national protocol guideline - for the treatment of obstetric spinal hypotension.
Detailed Description

Spinal anaesthesia is currently standard of care for patients undergoing caesarean section. Obstetric spinal hypotension is a common and important problem, related to important maternal and foetal outcomes. The prevention and treatment of spinal hypotension has been well researched in resource-rich settings, a context different from that encountered in the South African setting. It has been previously shown that a prophylactic phenylephrine infusion is effective in resource-limited settings, but this method is still dependent on the availability of an infusion pump.The ideal dose offering the best risk to benefit profile is 25 to 50 mcg/min. It has recently been shown that a prophylactic phenylephrine infusion, administered by an infusion pump, appears safe and effective in resource-constrained environments. However, some institutions in South Africa are limited by a lack of available infusion pumps. There is an urgent need to translate these research findings into a pragmatic management strategy that is safe and effective where this equipment is lacking. A 18g Jelco allows flow of approximately 100 ml/min in the absence of a pressure bag: therefore with 500 mcg in 1000 ml of ringers lactate and a fully opened line, a maximum dose of 50 mcg.min-1 will be achieved. If the rate is 50 ml/min (20 minutes for the first litre) the dose will be 25 mcg.min-1. This dose range will offer maximum benefit with low risk of side effects.

This exploratory study will establish if a phenylephrine (500 mcg) bolus, added to the first litre of Ringers lactate given as a co-load, is an effective and safe means to prevent post obstetric spinal hypotension. This regime will be compared to the existing South African national protocol of the management of obstetric spinal hypotension. The findings of this study will provide valuable information regarding a safe and potentially effective means to prevent obstetric spinal hypotension.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Single centre prospective alternating intervention study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cesarean Section Complications
  • Anesthesia Complication
Intervention  ICMJE Drug: Phenylephrine
Prophylactic phenylephrine infusion as part of fluid coload
Other Name: Phenylephrine coload
Study Arms  ICMJE
  • No Intervention: Bolus group
    Hypotension occurring under spinal anaesthesia (SBP < 90mmHg) requires pharmacological treatment. The pharmacological management of hypotension, once diagnosed, will be the same regardless of the protocol being used. If the heart rate is greater than 70 beats per minute, phenylephrine will be administered in a dose of 50-100 mcg as an intravenous bolus. If the heart rate is less than 70 beats per minute, ephedrine will be administered in a dose of 5-10 mg. The dose within this range will be decided by the attending anaesthetist. In both arms, Ringers Lactate fluid should run fast if hypotension occurs.
  • Active Comparator: Phenylephrine coload group
    Phenylephrine 500ug will be added to the first litre of ringer's lactate infused on initiation of spinal anaesthesia. If the phenylephrine infusion protocol is being used, and the mean arterial pressure (MAP) rises to greater than 20% of the initial MAP, and where this rise in MAP is not due to a recent bolus of either phenylephrine or ephedrine (within 2 minutes), the Ringers Lactate infusion will be switched off. The pharmacological management of hypotension, once diagnosed, will be the same regardless of the protocol being used. If the heart rate is greater than 70 beats per minute, phenylephrine will be administered in a dose of 50-100 mcg as an intravenous bolus. If the heart rate is less than 70 beats per minute, ephedrine will be administered in a dose of 5-10 mg. In both arms, Ringers Lactate fluid should run fast if hypotension occurs.
    Intervention: Drug: Phenylephrine
Publications *
  • Kinsella SM, Carvalho B, Dyer RA, Fernando R, McDonnell N, Mercier FJ, Palanisamy A, Sia ATH, Van de Velde M, Vercueil A; Consensus Statement Collaborators. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018 Jan;73(1):71-92. doi: 10.1111/anae.14080. Epub 2017 Nov 1.
  • Bishop DG, Rodseth RN, Dyer RA. Recipes for obstetric spinal hypotension: The clinical context counts. S Afr Med J. 2016 Aug 1;106(9):861-4. doi: 10.7196/SAMJ.2016.v106i9.10877. Review.
  • Bishop DG, Cairns C, Grobbelaar M, Rodseth RN. Prophylactic Phenylephrine Infusions to Reduce Severe Spinal Anesthesia Hypotension During Cesarean Delivery in a Resource-Constrained Environment. Anesth Analg. 2017 Sep;125(3):904-906. doi: 10.1213/ANE.0000000000001905.
  • Allen TK, George RB, White WD, Muir HA, Habib AS. A double-blind, placebo-controlled trial of four fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for cesarean delivery. Anesth Analg. 2010 Nov;111(5):1221-9. doi: 10.1213/ANE.0b013e3181e1db21. Epub 2010 May 21. Erratum in: Anesth Analg. 2011 Oct;113(4):800.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 1, 2019)
300
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 31, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All ASA 1-2 patients undergoing elective caesarean

Exclusion Criteria:

  • ASA grade >2 Hypertensive disease in pregnancy Dysrhythmia Failed spinal requiring conversion to a general anaesthetic
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04005664
Other Study ID Numbers  ICMJE BE616/17
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No sharing plans
Responsible Party University of KwaZulu
Study Sponsor  ICMJE University of KwaZulu
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David G Bishop, PhD University of KwaZulu
PRS Account University of KwaZulu
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP