Granisetron Versus Ondansetron: Comparative Effects on ECG, QTc
Condition: Prolonged QTc Interval
Study type: Interventional
Phase: Phase 4

Summary: 
      Postoperative nausea and vomiting [PONV] are common and distressing symptoms after surgery
      performed under general anaesthesia. 5HT3 antagonists are routinely used for prevention as
      well as treatment of PONV. After IRB approval we compared the effects of ondansetron and
      granisetron on the various intervals on ECG in 70 patients undergoing elective surgery for
      carcinoma breast after written informed consent. The demographic data was collected. The
      administration of the anaesthetic was left to the discretion of the operating room staff
      specialist. In the Postoperative Recovery Room patients were randomised to receive 8 mgs of
      ondansetron or 1 mg of granisetron intravenously. Serial ECGs were recorded at 0 mins (before
      injection of study drug), 2 mins, 5 mins, 15mins, 1 hour and 2 hours. Pulse rate,
      Non-invasive blood pressure and SpO2 were also recorded. T
    

Detailed description: 
      This prospective, randomized, single blind study was conducted after our Institutional Review
      Board approved the study protocol, consent form and the randomization form. 70 consecutive
      ASA I-III patients (age18 to 60 years) undergoing breast surgery for carcinoma breast were
      included in the study after obtaining written informed consent. Patients refusing consent,
      with prolonged QTc interval, with arrhythmias or conduction defects and those with abnormal
      serum levels of potassium, calcium, magnesium were excluded. There was no standardized
      anaesthesia technique. The technique of induction of anaesthesia, maintenance and reversal of
      anaesthesia was left to the discretion of the staff anaesthetist in the operating theatre.
      The data on comorbidities, preoperative medications for the comorbidities, premedication,
      induction agents, analgesics, muscle relaxants and inhalation agents was collected.

      Sample size calculation: A sample size calculation was performed [according to mean changes
      (difference of means) in QTc interval] to find out the number of patients needed to find a
      significant difference between the two drugs. To detect a QTc change from baseline of greater
      than 5 ms with α and β error of 0.05 and 0.20, respectively, and assuming an SD of QTc change
      of 10 ms using a one-sided test, a minimum of 35 subjects were needed in each antiemetic
      group.

      Randomization: The patients (n= 70) were divided randomly in two groups by computer generated
      random numbers by the statisticians in the Clinical Research Secretariat (CRS) in our
      institute. Block randomization was done with blocks of 10, to allow stratification of the
      patients depending on whether they had received anthracycline based neoadjuvant chemotherapy.
      The list of randomization numbers and clinical details were maintained in the CRS.

      Intervention: Once the patients arrived postoperatively in the recovery room, one of the
      investigators called the Clinical Research Secretariat (CRS) on phone, after completing the
      randomization form and gave the patient details. The Statistician allocated the drug the
      patient should receive which was prepared by the investigator which was either ondansetron 8
      mg (Group O) or granisetron 1mg (Group G). A baseline 12 lead electrocardiogram was obtained
      before the drug was administered. After baseline ECG, patients in Group O were given
      intravenous 8 mg ondansetron and patients in group G were given 1 mg granisetron over 30
      seconds. Subsequently serial 12 lead ECGs were done at 2 mins, 5 mins, 15mins, 1 hour and 2
      hours. Pulse, blood pressure and SpO2 were also monitored at those intervals. Unfiltered
      Electrocardiograms were recorded at paper speed of 25mm/sec and at normal amplitude with a HP
      Vigilent Pagewriter 100TM device which automatically calculates and prints the heart rate and
      the duration of various ECG intervals. The investigators independently read and analyzed the
      ECG to confirm that the intervals obtained with the ECG machine were indeed accurate. QT and
      R-R intervals were measured for calculation of corrected QT (QTc) interval. The corrected QT
      (QTc) interval was calculated by using the formula described by Bezzet. [QTc = QT interval/√
      (RR interval)]
    

Intervention name(s): Ondansetron; Granisetron
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous Ondansetron 8 mgs; Intravenous Granisetron 1 mgs
Other intervention name(s): 5HT3 antagonists; 5HT3 antagonists
Intervention MeSH terms: Ondansetron; Granisetron; Serotonin 5-HT3 Receptor Antagonists
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Postoperative nausea and vomiting; Ondansetron; Granisetron; QTc interval