Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202010907549506 Date of Approval: 06/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Opioid-free general anesthesia for Transthoracic Oesophagectomy; Does it improve postoperative analgesia and other recovery criteria? A prospective randomized study
Official scientific title Opioid-free general anesthesia for Transthoracic Oesophagectomy; Does it improve postoperative analgesia and other recovery criteria? A prospective randomized study
Brief summary describing the background and objectives of the trial A transthoracic oesophagectomy, also known as an Ivor Lewis oesophagectomy, is a procedure in which part of the esophagus is removed. Through an abdominal incision and a right thoracotomy incision. The cancerous portion of the esophagus is removed, along with the surrounding lymph nodes and a small margin of healthy tissue above and below the tumor. The stomach is made into a cylinder, pulled up into the chest and connected to the remaining section of the esophagus. Although esophageal cancer is a highly fatal cancer, with the sixth highest cancer-related mortality rate [1] Research data on esophageal cancer is limited compared to that of other cancers. [2] Enhanced recovery after surgery (ERAS), an important care pathway to effectively facilitate early recovery in postoperative patients, has short-term benefits including reduced hospital stay after esophageal cancer surgery. Two key components of ERAS are the maintenance of effective pain control while reducing excessive opioid use and a reduction of postoperative complications. [3,4] Recent findings from retrospective clinical trials, as well as experimental studies strongly suggest that opioids may inhibit cellular immunity through their effects on natural killer cell activity, stimulate angiogenesis and accentuate cancer cell growth. Hence, perioperative use of opioids might affect long-term oncological outcomes in the cancer surgical patients. This explains the current trend to use non-opioid drugs as an alternative to opioids for pain management during the perioperative period. [5] Postoperative opioid use and postoperative complications after esophageal cancer are closely related because opioid use itself may cause postoperative complications, and patients with postoperative complications generally require more opioids. [6, 7] Opioid-Free Anaesthesia (OFA) is a procedure that avoids opioid use during anaesthesia. A combination of several drugs including alpha-2-agonist, low-dose of N-Methyl-D-Asparate (NMDA) antagonist and lidocaine are added to usual hypnotic drug. Modulating peripheral afferent noxious stimulation, these agents may potentiate analgesic effects of opioid. (8) The primary goal of this study will be assessment of the effectiveness of OFA in transthoracic oesophagectomy in comparison with opioid-based technique (OBA) regarding the postoperative pain profile assessed by the visual analogue score (VAS) for 6 hours. Our secondary goal is to compare between patients of both techniques regarding postoperative breathing profile (respiratory rate, O2 saturation and arterial blood gases), the incidence of postoperative complications (e.g nausea, vomiting and shivering), the incidence of postoperative agitation in addition to patient hemodynamics immediately post-extubation and for the next 6 hours.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Anaesthesia
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Diagnosis / Prognosis
Anticipated trial start date 20/07/2020
Actual trial start date 20/07/2020
Anticipated date of last follow up 20/10/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group opioid based anesthesia group B Participants of opioid based group (B) will receive Fentanyl 1µg/kg diluted in 20 ml of saline 0.9% over ten minutes immediately before induction of anesthesia, then after induction of anesthesia patients will receive a bolus of fentanyl 1µg/Kg diluted in 10 cc saline 0.9% followed by maintenance by continuous infusion of Fentanyl 0.4µg/kg/hr diluted in 50 ml of saline 0.9% continuous intravenous infusion all through the surgery and stopped immediately after end of surgery Anesthetic Protocol All participants will be admitted to operating theatre (OR) induction area where patient identification is confirmed and an 18-gauge intravenous cannula will be inserted to all Participants. Participants in group (A) will receive Dexmeditomedine 1 µg/ Kg diluted in 20 cc saline 0.9% over 10 minutes immediately before induction of anesthesia, General anesthesia will be induced with intravenous propofol 2.0 mg/kg, Rocuronium 0.5 mg/Kg then double lumen endotracheal tube will be inserted orally and will be fixed after confirmation of its place by capnography and auscultation before and after patient positioning. All patients will receive 8 mg dexamethasone IV and magnesium sulphate 40 mg/Kg IV slowly immediately after induction. In group (B) a bolus of fentanyl 1µg/Kg diluted in 10 cc saline 0.9% followed by maintenance by continuous infusion of Fentanyl 0.4µg/kg/hr diluted in 50 ml of saline 0.9%. 15 Active-Treatment of Control Group
Experimental Group opioid free anesthesia group A Participants of opioid based group (A) will receive Dexmeditomedine 1 µg/ Kg diluted in 20 cc saline 0.9% over 10 minutes immediately before induction of anesthesiathen after induction of anesthesia patients will receive ketamine 0.5 mg/Kg and lidocaine 1 mg/Kg IV in 10 cc saline 0.9% followed by maintenance by continuous infusion of a mixture of 50 µg Dexmeditomedine with 50 mg ketamine and 500 mg lidocaine in 50 cc syringe will be infused as maintenance 1 ml/ 10 Kg/ hour where the doses will be (0.1µg/Kg/h Dexmeditomedine, 0.1 mg/Kg/h ketamine and 1 mg/kg/h lidocaine). continuous intravenous infusion all through the surgery and stopped immediately after end of surgery Anesthetic Protocol All participants will be admitted to operating theatre (OR) induction area where patient identification is confirmed and an 18-gauge intravenous cannula will be inserted to all Participants. Participants in group (A) will receive Dexmeditomedine 1 µg/ Kg diluted in 20 cc saline 0.9% over 10 minutes immediately before induction of anesthesia, General anesthesia will be induced with intravenous propofol 2.0 mg/kg, Rocuronium 0.5 mg/Kg then double lumen endotracheal tube will be inserted orally and will be fixed after confirmation of its place by capnography and auscultation before and after patient positioning. All patients will receive 8 mg dexamethasone IV and magnesium sulphate 40 mg/Kg IV slowly immediately after induction. patients will receive ketamine 0.5 mg/Kg and lidocaine 1 mg/Kg IV in 10 cc saline 0.9% followed by maintenance by continuous infusion of a mixture of 50 µg Dexmeditomedine with 50 mg ketamine and 500 mg lidocaine in 50 cc syringe will be infused as maintenance 1 ml/ 10 Kg/ hour where the doses will be (0.1µg/Kg/h Dexmeditomedine, 0.1 mg/Kg/h ketamine and 1 mg/kg/h lidocaine). 15
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Patients age range between 18- 64 years candidates for elective transthoracic oesophagectomy forced vital capacity (FVC) or force expiratory volume 1 (FEV1) ≥ 60% of the predicted values. Patients age below 18 years or above 64 years old History of thoracic trauma FVC or FEV1 ≤ 60% of predicted values History of obstructive sleep apnea or need for home CPAP mask Severe hypertension Uncontrolled diabetes mellitus Severe cardiovascular, renal or hepatic diseases History of analgesic administration or intake during past 24 hours Pregnant females History of relevant drug allergy. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 64 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/06/2020 Ain Shams University Faculty of medicine Ethic Research RECResearch General Surgery Department
Ethics Committee Address
Street address City Postal code Country
Ramsis street, Abbasya Cairo 11591 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary goal of this study will be assessment of the effectiveness of OFA in transthoracic oesophagectomy in comparison with opioid-based technique (OBA) regarding the postoperative pain profile assessed by the visual analogue score (VAS) for 6 hours (0 = no pain, 1 - 3 = mild pain, 4 - 6 = moderate pain, 7 - 10 = severe pain) immediately postextubation, 30 minutes in the PACU, 2, 4, and 6 hours cooperatively which are:immediately postextu
Secondary Outcome Respiratory rate and oxygen saturation will be recorded immediately before and after extubation and every 10 minutes for 30 minutes postoperative then it will be recorded every hour for the next 6 hours in the ICU. 0, 10, 20, 30 minutes after extubation then 1 , 2, 3, 4, 5, 6 hours pstoperative
Secondary Outcome Postoperative hemodynamics including mean heart rate (bpm) and MAP (mmHg) which will be recorded from the immediate postextubation, and every hour till the next 6 hours postoperatively 0, 1, 2, 3, 4, 5, 6 hours postoperatively
Secondary Outcome The incidence of postoperative hypoxia (Spo2≤ 90%) to which oxygen (6-10 L) via face mask will be applied during the first 6 hours postoperative and according to response to this step the patients will be assessed clinically by (respiratory rate, Spo2, ABG) for the need of mechanical ventilation either invasive or non-invasive. first 6 hours postoperative
Secondary Outcome Incidence of postoperative nausea and vomiting during the first 6 hours which will be treated by granisetrone 1mg intravenous. 0,1,2,3,4,5,6 hours postoperative
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
AinShams university hospitals Ramses street, Abbasia Cairo Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
tamer Nabil abdelrahman Ramsis street, Abbassia Cairo Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Tamer Nabil Abdelrahman 366, dr Mohamed Badawy st, 2nd district, 6th October city, Giza, Egypt 6th October city Egypt Individual
Primary Sponsor Wael Sayed Algharabawy 11/13 Zahraa Almaady street Cairo Egypt Individual
COLLABORATORS
Name Street address City Postal code Country
Wael Sayed Algharabawy Almaadi st, New Maadi Cairo Egypt
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Tamer nabil Abdelrahman tamernabil610@gmail.com +201288992910 366 Dr. Mohamed Badawy st, 2nd district, 6th October city
City Postal code Country Position/Affiliation
6th October city Egypt lecturer of anesthesia and intensive care and pain management at Faculty of medicine at Ain Shams university
Role Name Email Phone Street address
Public Enquiries Wael Algharbawy gharabawy76@yahoo.com 01096973949 Zahraa almaaddi street
City Postal code Country Position/Affiliation
Cairo Egypt Lecturer of anesthesia intensive care and pain faculty of medicine Ain Shams university
Role Name Email Phone Street address
Scientific Enquiries Hisham Akkad hisham_akkad@med.asu.edu.eg +201006890725 Ramsis streeat, Abbasya
City Postal code Country Position/Affiliation
Cairo 11591 Egypt Professor of surgery faculty of medicine at Ain Shams University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The Excel Sheets Statistical Analysis Plan,Study Protocol 12 months Editors of the journal to be submitted to
URL Results Available Results Summary Result Posting Date First Journal Publication Date
not available No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information