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Effect of Granisetron on Morphine Induced Pruritus in Cesarean Section

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ClinicalTrials.gov Identifier: NCT03483870
Recruitment Status : Not yet recruiting
First Posted : March 30, 2018
Last Update Posted : March 30, 2018
Sponsor:
Information provided by (Responsible Party):
Rabab Ahmed Samy Anwer, Assiut University

Brief Summary:

Neuraxial anesthesia, which includes epidural anesthesia and intrathecal anesthesia, is a frequent anesthetic approach for caesarean delivery and other lower abdominal and lower limb anesthetic procedures. The addition of neuraxial morphine to local anesthetics provides an effective and prolonged postoperative analgesia. Neuraxial administration of morphine which is considered as a gold standard for analgesia has been associated with a frequent incidence of pruritus and postoperative nausea and vomiting.

The incidence of neuraxial opioid induced pruritus varies widely from 30% - 60% after orthopedic surgery with intrathecal morphine injection and from 60% - 100% in pregnant women after neuraxial opioid administration. Parturients appear to be the most susceptible to neuraxial opioid-induced pruritus which probably might be due to the interaction of estrogens with opioid receptors.

Although the exact mechanism of neuraxial opioid induced pruritus is unclear, the postulated mechanisms include the presence of an "itch center" in the central nervous system (CNS), medullary dorsal horn activation, antagonism of inhibitory transmitters, modulation of 5-hydroxytryptamine subtype 3 (5-HT3) or serotonergic pathways and the involvement of prostaglandins.

There is dense concentration of opioid receptors and 5-HT3 receptors in the dorsal part of the spinal cord and the nucleus of the spinal tract of the trigeminal nerve in the medulla. Activation of these receptors by neuraxial opioid administration or by circulating estrogen in parturients results in neuraxial opioid induced pruritus which is usually localized to the face, neck, or upper thorax. Nalbuphine, propofol and ondansetron have been used effectively in the treatment of pruritus associated with neuraxial morphine in surgical patients.

Granisetron is a potent and highly selective 5-HT3 receptor antagonist that has little or no affinity for other 5-HT receptors, or dopaminergic, adrenergic, benzodiazepine, histaminic, or opioid receptors. Its onset of action is 1-3 min, peak plasma level 30 min, plasma half-life is 4-6 h and duration of action up to 24 h. Its longer duration of action than that of ondansetron may coincide with the peak incidence of pruritus after intrathecal morphine (6-9 h). In contrast, other 5-HT3-receptor antagonists have affinities for various receptor-binding sites. For example, ondansetron has detectable binding to 5-HT1B, 5-HT1C, α1-adrenergic, and μ-opioid receptor sites. Although not proven, the binding of these agents to additional receptor subtypes other than their target receptor may underlie the inferior adverse event profile seen with ondansetron compared with granisetron.


Condition or disease Intervention/treatment Phase
Pruritus Drug: Morphine Sulfate Drug: Placebo Drug: Granisetron Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: comparison of the effect of intravenous granisetron with the effect of using placebo on morphine induced pruritus in parturients undergoing elective cesarean section under spinal anesthesia.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) The trial will be planned that neither the doctors (investigator) nor the parturients will be aware of the group allocation. The study drugs will be prepared by an anesthesiologist not involved in performing the intrathecal anesthesia, patient care or in data collection.
Primary Purpose: Prevention
Official Title: Effect of Intravenous Granisetron on Incidence and Severity of Intrathecal Morphine Induced Pruritus in Elective Cesarean Section
Estimated Study Start Date : May 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Morphine sulphate & Placebo
20 parturients under intrathecal anesthesia will receive 200 ug morphine sulphate intrathecally and 2 mL of normal saline 0.9% (placebo) IV injection preoperative.
Drug: Morphine Sulfate
200 ug morphine sulphate will be injected intrathecally

Drug: Placebo
2 mL of normal saline 0.9% IV injection
Other Name: Normal saline 0.9%

Active Comparator: Morphine sulphate & Granisetron
20 parturients under intrathecal anesthesia will receive 200 ug morphine sulphate intrathecally and 2 mL of 2 mg granisetron IV injection preoperative.
Drug: Morphine Sulfate
200 ug morphine sulphate will be injected intrathecally

Drug: Granisetron
2 mL of 2 mg granisetron IV injection
Other Name: Kytril, Sancuso




Primary Outcome Measures :
  1. Incidence of pruritus during the first postoperative 24 hours. [ Time Frame: 24 hours ]
    The effect of prophylactic intravenous (IV) administration of granisetron on incidence and severity of pruritus that occurs after intrathecal morphine in parturients undergoing cesarean section (CS).


Secondary Outcome Measures :
  1. Onset time of pruritus [ Time Frame: 24 hours ]
    Recording the time when itching began

  2. The pruritus grading system (PGS) [ Time Frame: 24 hours ]

    The pruritus grading system (PGS) score (Firas et al, 2012) for each patient is based on: distribution, frequency, severity of itch and quality of sleep.

    Each patient's itch grade is calculated as the sum of the individual scores as:

    Distribution:Solitary site 1, Multiple sites 2, Generalized 3

    Frequency: Episodic 1, Frequent 3, Continuous 5

    Severity: Rubbing 1, Scratching 1, Localized excoriations 3, Generalized excoriations 5

    Sleep disturbance: Rare 0, Occasional 2, Frequent 4,Totally restless 6

    Mild grade: if total score is between 0 and 5.

    Moderate grade: if total score is between 6 and 11.

    Severe grade: if total score is between 12 and 19.


  3. Postoperative pain assessment [ Time Frame: 24 hours ]

    Postoperative pain assessment, by a blinded Post-Anesthesia Care Unit (PACU) nurse using VAS at 6, 12, 18 and 24 hours after intrathecal morphine injection. Visual analog scale is a validated approach to pain measurement (Wood, 2004). The most common VAS consists of a 10-cm line with one end labeled "no pain" and the other end labeled "worst pain imaginable." The patient marks the line at the point that best describes the pain intensity. The length of the line to the patient's mark is measured and recorded in millimeters. The main theoretical advantage of the VAS is that it does not limit pain to 10 discrete levels of intensity, permitting a more detailed rating of pain.

    Rescue analgesia will be given in the form of perfalgan (paracetamol) 1 gm/ 6 h (max 4 gm per day) IV infusion and/or pethidine (meperidine) 1 mg/ kg IM when VAS is greater than 4.


  4. Perioperative adverse events [ Time Frame: 24 hours ]
    Nausea, vomiting, intraoperative shortness of breath and respiratory depression (RR < 8 breaths/ min), and postoperative headache in the first 24 hours postoperatively.

  5. Participants' satisfaction after end of the delivery [ Time Frame: 24 hours ]
    1) not satisfied or 2) satisfied and willing to take the same medication and procedure in the future when indicated.



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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Parturients of American Society of Anesthesiologists (ASA) class I or II physical status.
  • Age: 20-40 years.
  • At term gestation (≥ 37 weeks) with a singleton uncomplicated pregnancy.
  • Elective cesarean delivery under intrathecal anesthesia.

Exclusion Criteria:

  • Parturient refusal.
  • Significant organ dysfunctions (e.g., cardiac, respiratory, renal, or liver disorders).
  • Morbid obesity (BMI >35).
  • Parturients with known hypersensitivity to granisetron, morphine or amide local anesthetics.
  • Parturients with pruritogenic systemic disease.
  • A coexisting skin disorder or preexisting pregnancy induced pruritus.
  • Parturients with any contraindication for intrathecal anesthesia, e.g. coagulopathy.
  • Emergency cesarean section.
  • Psychiatric disorders.
  • Fetal abnormalities.
  • Failed or unsatisfactory intrathecal block.

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): NCT03483870


Contacts
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Contact: ahmed elminshawy, prof 2332278 ext 088 ethics_committee12@yahoo.com

Locations
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Egypt
Assiut University Hospital Recruiting
Assiut, Egypt
Contact: ahmed elminshawy, prof    2332278 ext 088    ethics_committee12@yahoo.com   
Sponsors and Collaborators
Assiut University

Additional Information:
Publications of Results:

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Responsible Party: Rabab Ahmed Samy Anwer, Principal Investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03483870     History of Changes
Other Study ID Numbers: Granisetron in C.S
First Posted: March 30, 2018    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Rabab Ahmed Samy Anwer, Assiut University:
Granisetron, serum serotonin, morphine
Additional relevant MeSH terms:
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Pruritus
Skin Diseases
Skin Manifestations
Signs and Symptoms
Morphine
Granisetron
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action