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Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia

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ClinicalTrials.gov Identifier: NCT04401345
Recruitment Status : Recruiting
First Posted : May 26, 2020
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Rajesh Deshar, B.P. Koirala Institute of Health Sciences

Tracking Information
First Submitted Date  ICMJE May 20, 2020
First Posted Date  ICMJE May 26, 2020
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE June 1, 2020
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2020)
Total vasopressors requirement intraoperatively [ Time Frame: immediately after spinal anaesthesia till the end of the surgery ]
Total vasopressors required to prevent hypotension during the period of surgery
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2020)
  • The incidence of hypotension [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    Hypotension is defined as systolic blood pressure < 80% of baseline reading or systolic blood pressure < 100 mmHg
  • The incidence of reactive hypertension [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    defined as systolic blood pressure > 120% of baseline reading
  • The incidence of maternal bradycardia [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    heart rate < 55/min
  • The incidence of maternal tachycardia [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    Heart rate > 100/min
  • The incidence of nausea [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    Patients will be asked to report the occurrence of intraoperative nausea and rate its severity using an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea).
  • The incidence of vomiting [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    incidence of vomiting
  • The incidence of shivering [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    Shivering will be graded as: 0 no shivering, 1 one or more of the following: piloerection, peripheral vasoconstriction, peripheral cyanosis without other cause, but without visible muscular activity; 2 visible muscular activity confined to one muscle group; 3 visible muscular activity in more than one muscle group; and 4 gross muscular activity involving the whole body
  • The incidence of dry mouth, intraoperative pruritus and dizziness [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    incidence of dry mouth, intraoperative pruritus and dizziness
  • Maternal heart rate and [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    to record the heart rate of the patient during surgery
  • Maternal systolic blood pressure [ Time Frame: after spinal anaesthesia till the end of the surgery ]
    to record systolic blood pressure of the patient during surgery
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 23, 2020)
  • The APGAR outcome of baby [ Time Frame: at 1 and 5 min after delivery ]
    APGAR score comprises of 5 criteria : a) Appearance b) Pulse Rate c) Reflex d)Muscle tone e) Respiratory Effort with each criteria of score 0,1 or 2; making total score of 10. Score 7-10 is reassuring, 4-6 moderately normal, 0-3 is low and cause for immediate resuscitative efforts
  • Need for neonatal resuscitation [ Time Frame: immediately after delivery ]
    resuscitation needed for baby
  • Admission to neonatal ICU (NICU) [ Time Frame: after delivery ]
    the need for ICU admission
  • Neonatal death [ Time Frame: within 30 days of delivery ]
    if there is neonatal death or not
Original Other Pre-specified Outcome Measures
 (submitted: May 20, 2020)
  • The APGAR outcome of baby [ Time Frame: at 1 and 5 min after delivery ]
    APGAR score
  • Need for neonatal resuscitation [ Time Frame: immediately after delivery ]
    resuscitation needed for baby
  • Admission to neonatal ICU (NICU) [ Time Frame: after delivery ]
    the need for ICU admission
  • Neonatal death [ Time Frame: within 30 days of delivery ]
    if there is neonatal death or not
 
Descriptive Information
Brief Title  ICMJE Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia
Official Title  ICMJE Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia
Brief Summary This is prospective randomised double blind study conducted in parturients planned for non-elective caesarean section under spinal anaesthesia. Glycopyrrolate group will receive 0.2 mg of Glycopyrrolate before start of phenylephrine infusion. Control group will receive 0.2 ml of Normal Saline before start of phenylephrine infusion. Total amount of vasopressors required i.e. ephedrine or phenylephrine will recorded in the form of phenylephrine equivalent during intraoperative period.
Detailed Description

Intravenous glycopyrrolate has been investigated for its effect on haemodynamic changes after spinal anesthesia for caesarean delivery. Results from previous studies are conflicting as glycopyrrolate has shown to reduce, increase or had no effect on incidence of maternal hypotension and/or vasopressor requirement after spinal anaesthesia. A recent meta-analysis found that prophylactic glycopyrrolate does not prevent the incidence of spinal-induced hypotension; however, it reduces the total vasopressor requirement during elective caesarean delivery under spinal anaesthesia. Therefore, the aim of this study is to find out whether the use of glycopyrrolate decreases the amount of vasopressors required to manage hypotension induced by spinal anaesthesia in non-elective CS.

Methodology:

After approval from Institutional Review committee of B.P. Koirala Institute of Health Sciences, the trial will be registered at clinical trial.gov. Parturient planned for non-elective caesarian of ASA PS grade II fulfilling the inclusion criteria will be informed about the study and written consent will be obtained either in labour room or in obstetric emergency ward. The eligible patients will be randomly assigned to Glycopyrrolate (GP group) or normal saline (NS group). The study will be conducted in accordance with the ethical principles of the 1964 Declaration of Helsinki. Before patient is shifted to the operating room (OR), ranitidine 50 mg and metoclopramide 10 mg will be administered intravenously via 18 G cannula. In the operating table, patients will be laid supine with a wedge placed in the right hip. Standard anaesthesia monitoring including 3-lead electrocardiography, heart rate (HR), noninvasive blood pressure (NIBP) and pulse oximetry (Sp02) will be done. A mean value of three measurements of systolic blood pressure (SBP) and HR will be recorded as baseline parameters. Patency of the vein will be maintained with the infusion of Ringer's lactate solution at a minimal rate.

Before the patient is placed in sitting position for SA,she will receive the study drug according to the randomization. After free flow of CSF is observed, 0.5 % hyperbaric bupivacaine (2.2 ml) with 10 µg fentanyl will be injected intrathecally over 30 s using a 25-gauge Quinke needle at the L3-4 or L4-L5 interspace. Patients will then be immediately placed in supine while maintaining 15 degree left lateral tilt. Co-loading of 1000 ml ringers lactate solution will be initiated at the start of spinal anaesthesia using a pressure bag and it will be completed within 10 min. Immediately after the spinal injection, phenylephrine infusion will be initiated at a rate of 25 µg/min and it will be titrated to maintain maternal SBP within 20 % of baseline.

The sensory level of anaesthesia will be checked using loss of cold sensation. Surgery will be allowed once the bilateral sensory block height at T6 is achieved. Oxygen at 40% will be administered via nasal cannula at 2-4 L/min until delivery.

Hemodynamic parameters will be recorded at following time intervals: baseline, after the study drug in given IV, immediately after spinal anaesthesia, every minute for first 10 min, and then at 2.5 min until end of surgery. Post-spinal hypotension will be defined as SBP < 80% of baseline reading or SBP < 100 mmHg before delivery of baby. Post-delivery hypotension is defined as SBP < 80% of baseline reading or SBP < 100 mmHg after delivery of the baby. It will be treated with phenylephrine 100 µg bolus and rapid infusion of Ringer's lactate 200 ml. Infusion of phenylephrine will be stopped if bradycardia (HR< 55/min) occurs without hypotension. If bradycardia (HR< 55/min) is associated with hypotension, IV ephedrine 6 mg will be administered. If these measures fail and bradycardia is still persistent then an IV atropine 0.5 mg will be given. If reactive hypertension (defined as SBP > 120% of baseline reading) occurs, the infusion of phenylephrine will be stopped and restarted only when the SBP reaches the target range (SBP is within 120% of baseline SBP). The amount of ephedrine used will be converted to phenylephrine equivalent based on potency of phenylephrine to ephedrine as 81:1 ratio.(31)

After delivery of the baby, 2 U of oxytocin will be administered IV over 5-10 sec followed by an infusion of 10 U/hr (oxytocin 20 U in 500 ml of Hartmann's solution). Phenylephrine infusion will be gradually tapered after delivery of the baby keeping the SBP within the target level. The total amount of intraoperative IV fluids administered and estimated blood loss will be measured. Intraoperative use of other uterotonic agent or blood transfusion will be recorded. The attending pediatrician will assess neonatal Apgar scores at 1 and 5 minutes after delivery.

Patients will be asked to report the occurrence of intraoperative nausea and rate its severity using an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea). Intraoperative nausea or vomiting (IONV) will be treated with ondansetron 4 mg IV. After 5 min, if nausea and vomiting is still persisted, IV dexamethasone 4 mg will be administered. IONV incidence and its time of occurrence from intrathecal injection (whether associated with hypotension) and antiemetic needed will be recorded. Incidence of intraoperative pruritus, shivering, dizziness and dry mouth will also be recorded. Grading of intraoperative shivering is as follows: 0 no shivering, 1 one or more of the following: piloerection, peripheral vasoconstriction, peripheral cyanosis without other cause, but without visible muscular activity; 2 visible muscular activity confined to one muscle group; 3 visible muscular activity in more than one muscle group; and 4 gross muscular activity involving the whole body. If the shivering score is ≥3, IV meperidine 20 mg will be given.

The primary outcome will be the total amount of phenylephrine used to maintain blood pressure intraoperatively. The secondary outcome measures will include incidence of maternal hypotension, reactive hypertension, bradycardia, other side-effects (IONV, shivering, pruritus, dry mouth,dizziness), changes in maternal SBP and heart rate and neonatal outcome (Apgar scores at 1 min and 5 min, requirement of neonatal resuscitation, need for neonatal ICU admission and neonatal death within 30 days).

Data collection:

Baseline data (gestational age, uterine incision to delivery time, hemodynamic parameters) and outcome parameters will be collected in the paper case record form and entered in windows Microsoft excel spreadsheet for analysis.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Experimental Group (GP): In the experimental group patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated.

Placebo Group (NS): In the placebo group patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Glycopyrrolate and normal saline will be administered as 1 ml clear fluid, and therefore, both patient and investigator will be blinded to the randomization and intervention.
Primary Purpose: Prevention
Condition  ICMJE
  • Glycopyrrolate
  • Post-spinal Hypotension
  • Effect of Drug
  • Hemodynamic Instability
Intervention  ICMJE
  • Drug: Glycopyrrolate 0.2 MG/ML
    In this group, the patients will receive glycopyrrolate 0.2 mg in 1 ml
    Other Name: Glycopyrronium bromide
  • Drug: Normal saline
    In this group, the patients will receive 1 ml of 0.9% normal saline
    Other Name: 0.9% NS
Study Arms  ICMJE
  • Experimental: Experimental Group (GP)
    Patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated at 25mcg/min.
    Intervention: Drug: Glycopyrrolate 0.2 MG/ML
  • Placebo Comparator: Placebo Group(NS)
    patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated at 25 mcg/min
    Intervention: Drug: Normal saline
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2020)
258
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2021
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age between 18-40 years
  • All parturients at term (gestational weeks ≥ 37)
  • ASA (American society of Anaesthesiologist) PS (Physical status) grade II

Exclusion Criteria:

  • Age >40 year
  • ASA PS Grade >2
  • Maternal bradycardia (baseline HR< 60/min) or tachycardia (baseline HR> 100/min)
  • Pregnancy induced hypertension
  • Gestational hypertension
  • Known fetal abnormalities
  • Intrauterine growth retardation (IUGR)
  • Intrauterine fetal death (IUFD)
  • Contraindications to spinal anaesthesia
  • Contraindications to glycopyrrolate
  • Multiple pregnancy
  • BMI: > 30 kg/m2
  • Height: <150cm
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rajesh Deshar, MD/MS 9849808093 raz.deshar@gmail.com
Contact: Asish Subedi, MD/MS 9842040604 asishsubedi19@gmail.com
Listed Location Countries  ICMJE Nepal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04401345
Other Study ID Numbers  ICMJE IRC/1603/019
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
Responsible Party Rajesh Deshar, B.P. Koirala Institute of Health Sciences
Study Sponsor  ICMJE Rajesh Deshar
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account B.P. Koirala Institute of Health Sciences
Verification Date June 2020

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