Granisetron vs Granisetron and Dexamethasone on the Reduction of Postoperative Nausea and Vomiting

• ClinicalTrials.gov Identifier: NCT04570592
• Recruitment Status: Recruiting
• First Posted: September 30, 2020
• Last Update Posted: September 30, 2020
• Sponsor: Universiti Sains Malaysia
• Information provided by (Responsible Party): Farah Nasuha Mohd Daut, Universiti Sains Malaysia

Study Description

Brief Summary:

Intrathecal morphine (ITM) has proven to be excellent in reducing postoperative pain. However, its use has commonly been associated with the occurrence of postoperative nausea and vomiting (PONV). In recent years, the combination therapy of antiemetics comprising of a serotonin receptor antagonist and corticosteroid has been implemented to diminish the occurrence of PONV. Despite being routinely used, the evidence in the efficacy of this combination in parturients are conflicting and lacking. In this study, we wish to compare the efficacy between the combination therapy of granisetron plus dexamethasone versus granisetron alone on the occurrence of postoperative nausea and vomiting (PONV) in 126 parturients undergoing elective Caesarean delivery supplemented with intrathecal morphine.

Condition or disease	Intervention/treatment	Phase
PONV	Drug: Granisetron 1 Mg/mL Intravenous Solution And Dexamethasone 4mg; Drug: Granisetron 1 Mg/mL Intravenous Solution	Phase 2

Detailed Description:

126 parturients aged between 18 and 45 years old who falls within the American Society of Anaesthesiology (ASA) physical status I and II undergoing Caesarean deliveries from the 1st of October 2020 till the 1st of April 2021 will be enrolled. Informed and written consent shall be obtained on recruitment.

Subjects will be randomised using a computer-generated randomisation software using block size 3 into 2 groups; group A and group B each consisting of 63 subjects. The order of interventions within each block was random as determined by computer random number generator. This technique was chosen to ensure similar numbers of patients in each group at any point during the study. Both patients and the assessors of PONV which is the Acute Pain Service (APS) team will be blinded.

Patients are subjected to fasting 6 hours prior to surgery with clear fluid allowed up to 2 hours before surgery. Intravenous (IV) metaclopromide 10mg, IV ranitidine 50mg and mist sodium citrate 30 mls will be administered as part of the acid aspiration prophylaxis. Standard monitoring with continuous noninvasive blood pressure monitoring (NIBP), electrocardiogram (ECG), respiratory rate and pulse oximetry (SpO2) will be implemented throughout anaesthesia.

Ringer's lactate solution 10ml/kg will be infused for coloading to mitigate hypotension post spinal anaesthesia. Spinal anaesthesia will be administered in the upright position, implementing a height-based dose for heavy bupivacaine 0.5% administration. Based on the subject's height, those who are less than 150cm, 151-154cm and those who are more than 155cm will receive 1.5mls, 1.7mls and 1.9mls heavy bupivacaine 0.5% (AstraZeneca) respectively. Fentanyl 15-20 mcg and morphine 0.1 mg are added to supplement the spinal anaesthesia.

On the completion of spinal anaesthesia, 4 mg of dexamethasone will be administered to parturients in group A while group B received 1ml of normal saline injected intravenously. 1mg of IV granisetron will be administered to both groups of subjects after cord clamping. These drugs will be given by the anaesthetist administering the spinal anaethesia. The anaesthetist in charge is not blinded as this is of paramount importance in ensuring patients safety should any complication arises during the delivery of anaesthesia.

Post surgery, subjects will be monitored in the recovery area for an hour. To supplement ITM as the postoperative analgesia, tablet paracetamol 1g qid and voltaren 50mg tds will be provided to patients postoperatively. The use of opioid is avoided during the first 24 hours of intrathecal morphine administration. Patients will be monitored for complications of ITM for 24 hours and assessments will be carried out by the APS team which include an anaesthetic medical officer and 2 staff nurses.

Assessments are made at 1 hour post surgery, 4 hourly for 12 hours post surgery up to 24 hours after surgery. Episodes of nausea, retching and vomiting will be elicited by direct questioning and recorded at each assessors' visit. Nausea is described as an unpleasant sensation related to the urge to vomit. Retching is defined as an involuntary effort to vomit but without the expulsion of the gastric contents, while vomiting is the when expulsion of gastric contents occur.

The requirement of rescue antiemetics at each time interval will also be documented. Rescue antiemetic is given when a patient developed one or more episodes of vomiting. IV ondansetron 4 mg is given to group A while either IV dexamethasone 4mg or iv ondansetron is given to group B. Subsequent requirement of antiemetics will be decided based on the anaesthetist discretion.

Sample size is calculated based the assumption that the combination of a serotonin receptor antagonist with a corticosteroid would be superior than its monotherapy and thus, the addition of dexamethasone to granisetron would reduce the incidence of PONV from 20% to 3.3%. From the calculation using PS software, the sample required for each group is 57, and with the additional 10% for dropout rate, this study required 63 patients in each group, giving a total of 126 patients.

Data analysis will be performed using SPSS version 27 for MAC. The incidences of nausea, retching, vomiting and the use of rescue antiemetic will be analysed using Chi-Square test. Data is presented as percentage and a p-value of <0.05 is considered statistically significant.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Granisetron vs Granisetron and Dexamethasone on the Reduction of Postoperative Nausea and Vomiting After Caesarean Section With Intrathecal Morphine: A Randomized Controlled Trial
• Estimated Study Start Date: October 1, 2020
• Estimated Primary Completion Date: April 1, 2021
• Estimated Study Completion Date: June 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Granisetron; Granisetron 1 mg (1ml) + Normal saline 1ml	Drug: Granisetron 1 Mg/mL Intravenous Solution; Comparing PONV incidences in both arms
Experimental: Granisetron and Dexamethasone; Granisetron 1mg (1ml) + Dexamethasone 4mg (1ml)	Drug: Granisetron 1 Mg/mL Intravenous Solution And Dexamethasone 4mg; Comparing PONV incidences in both arms; Other Name: Treatment group

Outcome Measures

Primary Outcome Measures :

1. Comparing the incidence of post operative nausea and vomiting (PONV) [ Time Frame: From 1 to 24 hour post operatively ]
   To compare the incidence of nausea, retching and vomiting at 1 hour, 4 hourly for 12 hours and at 24 hours postoperatively between parturients receiving combination therapy of Granisetron plus Dexamethasone versus that of Granisetron alone

Secondary Outcome Measures :

1. Comparing the requirement of rescue antiemetic between both groups [ Time Frame: From 1 to 24 hour post operatively ]
   To compare the requirement of rescue antiemetic between 1 hour, 4 hourly for 12 hours and at 24 hours postoperatively between parturients receiving combination therapy of Granisetron plus Dexamethasone versus that of Granisetron alone

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Parturients
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• American Society of Anaesthesiologists (ASA) I-II category
• 2 risks factors or more for PONV according to Apfel Score.

Exclusion Criteria:

• Unfit for spinal anaesthesia.
• Coagulopathy
• Uncorrected hypovolemia
• Indeterminate neurologic disease
• Infection at site of injection
• Raised intracranial pressure(ICP)
• Morbidly obese patients, BMI> 40 kg/m2 according to ICD-10 (International Statistical Classification of Diseases 10)
• Patients allergic towards morphine.
• Contraindicated for antiemetics use
• Granisetron: allergy towards Granisetron, prolonged QT interval
• Ondansetron: allergy towards ondansetron, prolonged QT interval
• Dexamethasone: allergy towards Dexamethasone, uncontrolled Diabetes Mellitus (DM).

Contacts and Locations

Locations

Malaysia

Universiti Sains Malaysia, Health Campus; Recruiting

Kubang Kerian, Kelantan, Malaysia, 16150

Contact: Associate Professor W Mohd Nazarudin W Hassan 09-7673000 ext 6105 nazarudin@usm.my

Sponsors and Collaborators

Universiti Sains Malaysia

Investigators

• Principal Investigator: Farah Nasuha Mohd Daut; Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan

More Information

Publications of Results:

Abouleish E, Rawal N, Fallon K, Hernandez D. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg. 1988 Apr;67(4):370-4.

Other Publications:

Gwirtz KH, Young JV, Byers RS, Alley C, Levin K, Walker SG, Stoelting RK. The safety and efficacy of intrathecal opioid analgesia for acute postoperative pain: seven years' experience with 5969 surgical patients at Indiana University Hospital. Anesth Analg. 1999 Mar;88(3):599-604.

Sfeir S, Mansour N. Post operative analgesia with intrathecal morphine. Middle East J Anaesthesiol. 2005 Feb;18(1):133-9.

Dahl JB, Jeppesen IS, Jørgensen H, Wetterslev J, Møiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology. 1999 Dec;91(6):1919-27. Review.

Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004 Jun 10;350(24):2441-51.

• Responsible Party: Farah Nasuha Mohd Daut, Trainee Anaesthetist, Universiti Sains Malaysia
• ClinicalTrials.gov Identifier: NCT04570592
• Other Study ID Numbers: USM/JEPeM/1809426
• First Posted: September 30, 2020
• Last Update Posted: September 30, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: IPD will be considered for sharing if the data is to be used for related studies.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Farah Nasuha Mohd Daut, Universiti Sains Malaysia:

Caesarean; Morphine; Granisetron

Additional relevant MeSH terms:

Vomiting; Postoperative Nausea and Vomiting; Nausea; Signs and Symptoms, Digestive; Postoperative Complications; Pathologic Processes; Dexamethasone; Granisetron; Pharmaceutical Solutions; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action