Prophylactic Antiemetic Efficacy of Palonosetron Versus Ondansetron for the Prophylaxis of Postoperative Nausea and Vomiting (PONV) in Women Over 60 Years Undergoing Laparoscopic Cholecystectomy

Sponsor

Hospital Federal de Bonsucesso (Other)

Overall Status

Completed

CT.gov ID

NCT02541019

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Despite the development of new drugs, nausea and vomiting after surgery (PONV) are still frequent. Antagonists 5HT3 receptors, such as ondansetron and palanosetron, are among the main characterized prophylactic agents in patients at high risk, however there are few studies comparing the efficacy of these drugs and no study that addresses women aged over 60 years.

In this prospective, randomized, double-blind study, 80 women nonsmokers, undergoing laparoscopic cholecystectomy will be divided into two groups, receiving during anesthetic induction intravenous ondansetron 4 mg (n = 40) or palonosetron 75 mcg (n = 40) prophylaxis of PONV.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Nausea and Vomiting	Drug: Ondansetron Drug: Palonosetron	Phase 4

Detailed Description

Clinical, prospective, randomized double-blind trial will be conducted at the Federal Hospital Bonsucesso (HFB), Rio de Janeiro, Brazil. Eighty female patients, olther than 60 years, ASA I to III, undergoing laparoscopic cholecystectomy will be studied. They will be randomized into two groups of 40. One group will receive Palonosetron 75 mcg (Group P) and the other will receive Ondansetron 4mg (Group O). Patients will not receive premedication. Will be monitored in the operating room with non-invasive blood pressure, cardioscopy, pulse oximetry, capnography and bispectral index (BIS). After cannulation of peripheral vein, 10 ml of blood will be collected for further analysis. They will be given one minute before induction of anesthesia, intravenous (IV) bolus preparations of the studied antiemetics. Patients will be pre-oxygenated with oxygen at 100% for 5 minutes and the anesthetic induction is performed with intravenous administration of fentanyl 3 mcg / kg; Lidocaine 1.5 mg / kg and propofol 2 mg / kg. Tracheal intubation will be facilitated after 3 minutes of administration of Rocuronium 0.6 mg / kg EV .Maintenance of anesthesia will be with Sevoflurane 2 L / min in 50% oxygen / air, with its concentration adjusted to maintain BIS between 40-60. Remifentanil 0.05 mcg / kg / min to 0.2 mcg / kg / min IV can be administered intraoperatively if the heart rate or blood pressure to rise more than 20% of values baseline. Additional doses of rocuronium may also be administered as needed. Patients will receive paracoxibe 40 mg,dipirone 50 mg / kg and 50 mg of ranitidine IV after tracheal intubation and have the surgical wound infiltration with 20 mL of ropivacaine 0.5%, before the sutures. Neuromuscular blockade reversed with neostigmine 0.04 mg / kg and atropine 0.02 mg / kg IV at the end of surgery. Will be limited to insufflation of the pneumoperitoneum to abdominal pressure of 15 mmHg.

A non-participating physician will be aware of the research on which antiemetic was given and be responsible for postoperative prescription of patients. The researchers did not have access to prescription and medical records within 48 hours after surgery. Both groups will recive metoclopramide 10 mg (EV) as rescue medication for PONV, and the Group O will continue with prescription ondansetron 4 mg (EV) regular 8 / 8h, in the following 48 h after surgery. Patients will receive clinical visit by the research team 2, 6, 24 and 48 h after the end of surgery and will be questioned about the frequency and intensity of PONV, as well as other side effects. Finished the last evaluation, researchers will review the prescription and will note the use of opioids (type, dose, route of administration), use of rescue medication, total cost of antiemetic therapy (including 5HT3 antagonist and rescue medication), based on "Brasíndice" table.

All patients have their blood samples analyzed in the clinical research laboratory of the Universidade Federal Fluminense, for concurrent research of prevalence of polymorphisms of 5HT3 receptors and their correlation with the antiemetic effect. DNA will be extracted from blood samples using a kit to genomic DNA purification. Polymerase chain reaction test for real time will be applied below for analysis of single nucleotide polymorphisms of. The reactions are prepared with Genotyping according to the manufacturer's instructions and performed on a sequence detection system using standard thermal cycling conditions.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Prophylactic Antiemetic Efficacy of Palonosetron Versus Ondansetron for the Prophylaxis of Postoperative Nausea and Vomiting (PONV) in Women Over 60 Years Undergoing Laparoscopic Cholecystectomy

Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Jan 1, 2017

Actual Study Completion Date :

Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palonosetron Palonosetron (iv) one minute before anesthesic induction.	Drug: Palonosetron 75 mcg IV, one minute before the anesthesia induction.
Experimental: Ondansetron ondansetron (iv) one minute before anesthesic induction and ondansetron regular three times a day for two days after the surgery.	Drug: Ondansetron 4 mg IV, one minute before the anesthesia induction and 4 mg IV three times a day during two days after the surgery.

Arm

Intervention/Treatment

Experimental: Palonosetron

Palonosetron (iv) one minute before anesthesic induction.

Drug: Palonosetron

75 mcg IV, one minute before the anesthesia induction.

Experimental: Ondansetron

ondansetron (iv) one minute before anesthesic induction and ondansetron regular three times a day for two days after the surgery.

Drug: Ondansetron

4 mg IV, one minute before the anesthesia induction and 4 mg IV three times a day during two days after the surgery.

Outcome Measures

Primary Outcome Measures

Frequency and intensity of individual episodes of PONV. [48 h after surgery]

Secondary Outcome Measures

Intensity of nausea [during clinical visit 2, 6, 24 and 48 h postoperatively]
Evaluate nausea intensity in numeric scale (0-10) during clinical visit
Need of medication for antiemetic rescue [during the 48 h after surgery]
Assess the need of medication for antiemetic rescue during the 48 h after surgery
Number of complete responders to medication [during the 48 h after surgery]
Determine the number of complete responders to medications (no emetic episode or rescue medication during the 48 hours after surgery)
Degree of satisfaction with antiemetic therapy [during the 48 h after surgery]
Know the degree of satisfaction with antiemetic therapy, through the 5-point rating scale (very dissatisfied, dissatisfied, neutral, satisfied or very satisfied)
Cost of antiemetic medication [during the 48 h after surgery]
total cost of antiemetic therapy (including 5HT3 antagonist and rescue medication), based on the table "Brasíndice".
Frequency and intensity of adverse effects [during the 48 h after surgery]
Determine the frequency and intensity of adverse effects by means of numerical scale(0-10) (headache, dizziness, drowsiness and others)
Frequency of polymorphism of 5HT3a receptors and 5HT3b [participants will be followed for the duration of hospital stay, an expected average of 48 h]
To assess the frequency of polymorphism and 5HT3b 5HT3a receptors and their correlation with the frequency and intensity of antiemetic effect and adverse effects.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Will be selected patients aged over 60 years, ASA 1-3 that are candidates for laparoscopic cholecystectomy

Exclusion Criteria:

Participation in another study last month.
Body mass index> 35.
The occurrence of episodes of nausea or vomiting in the last 24 h prior to surgery.
Use of corticosteroids.
Smoking.
Alcoholism.
Use of psychoactive drugs or any other drug with antiemetic effect.
Known hypersensitivity to any study medication
Severe diseases in organs such as kidney, liver, lung, heart, brain and bone marrow.
Conversion laparoscopic cholecystectomy for conventional cholecystectomy.