Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06354478
Status:
COMPLETED
Last Update Posted:
2024-04-09
First Post:
2024-04-03
Brief Title:
IV Dexmedetomidine vs Oral Gabapentin and Their Combination for Postoperative Analgesia in Cancer Patients Undergoing Modified Radical Mastectomy
Sponsor:
National Cancer Institute Egypt
Organization:
National Cancer Institute Egypt
Study Overview
Official Title:
A Randomized Double-blind Study to Compare the Efficacy of Intravenous Dexmedetomidine Infusion Oral Gabapentin and Their Combination on Postoperative Analgesia in Cancer Patients Undergoing Modified Radical Mastectomy
Status:
COMPLETED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Breast cancer is the most common malignant tumour among females with an incidence of about 21 million women every yearNearly about 40-60 of breast surgery patients develop severe acute postoperative pain⁴ Opioids are the current best standard drugs for postoperative pain relief however exposure to large doses of opioids leads to multiple side effects like prolonged sedation respiratory depression nausea and vomitingWe are comparing two different drugs and their combination for perioperative analgesia for MRM
This work is a comparative study that aims to compare the analgesic effects of perioperative IV infusion of dexmedetomidine preoperative oral gabapentin and their combination in patients undergoing modified radical mastectomy surgery regarding the time of first rescue analgesia postoperative morphine consumption and possible complications
This work is a comparative study that aims to compare the analgesic effects of perioperative IV infusion of dexmedetomidine preoperative oral gabapentin and their combination in patients undergoing modified radical mastectomy surgery regarding the time of first rescue analgesia postoperative morphine consumption and possible complications
Detailed Description:
Introduction
Breast cancer is the most common malignant tumour among females with an incidence of about 21 million women every year It is the greatest cancer-related mortality among women approximately 15 of all cancer mortality In addition to that Egypt follows the international incidence with breast cancer being the most common malignancy among females with 18660 patients each year¹ Modified Radical Mastectomy MRM is one of the main surgical treatments of breast cancer Accordingly it is an account for 31 of all breast surgery cases² The common modality for anaesthesia for MRM is general anaesthesia with or without regional blocks³
Nearly about 40-60 of breast surgery patients develop severe acute postoperative pain⁴ Opioids are the current best standard drugs for postoperative pain relief however exposure to large doses of opioids leads to multiple side effects like prolonged sedation respiratory depression nausea and vomiting⁵ Moreover the use of opioids inhibits cell-mediated immunity with an increase in tumour angiogenesis cell migration and metastasis in addition to the progression of the cell cycle Therefore plans other than opioids are recommended without losing proper and effective analgesia especially in breast cancer patients who are more sensitive to develop opioid tolerance and addiction⁶ So it became a necessity to find safe analgesic techniques for these patients by using different techniques like adjuvant therapies or multimodal analgesia by combining different drugs with different mechanisms of action together to increase the quality of postoperative analgesia and to decrease the need for high doses of systemic opioids and their related side addiction⁷⁸
Alpha-2 agonists including clonidine and dexmedetomidine have been used perioperatively Dexmedetomidine is different from clonidine in two properties It has more affinity for the alpha-2 receptor 8 times that of clonidine and is easier to titrate⁹ Also dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has sedative analgesic anaesthetic-sparing properties without causing any respiratory depression¹⁰ Dexmedetomidine can be a good anaesthetic premedication because of its sympatholytic effect to attenuate the sympathetic stress response to perioperative stresses like laryngoscopy and intubation¹¹ The analgesic effect provided by dexmedetomidine is mediated mainly through interaction at alpha-2a within the spinal cord where drug activity attenuates nociceptive signal transduction And although dexmedetomidine when given alone has been documented to reduce pain it has a synergistic or additive effect when combined with opioids¹²
Another promising drug for postoperative pain management is gabapentin It binds to the α-2 δ subunit of voltage-gated calcium channels and preventing the release of nociceptive neurotransmitters like glutamate substance P and noradrenaline¹³ Evidence suggests that in addition to its effectiveness as an analgesic for patients with neuropathic pain and chronic pain syndromes gabapentin also provides effective postoperative analgesia when given before an operation¹⁴¹⁵ Therefore the combination of IV dexmedetomidine and oral gabapentin due to their analgesic effects would be more effective in reducing postoperative analgesic consumption and providing prolonged postoperative analgesia after a modified radical mastectomy
To the best of researchers knowledge comparing the effect of perioperative intravenous dexmedetomidine infusion preoperative oral gabapentin and their combination on the total consumption of intraoperative and postoperative opioids in patients undergoing modified radical mastectomy was not investigated before
Aim of the work
This work is a comparative study that aims to compare the analgesic effects of perioperative IV infusion of dexmedetomidine preoperative oral gabapentin and their combination in patients undergoing modified radical mastectomy surgery regarding the time of first rescue analgesia postoperative morphine consumption and possible complications
Objectives
To assess the analgesic outcomes of perioperative IV infusion of dexmedetomidine preoperative oral gabapentin and their combination in controlling acute postoperative pain in modified radical mastectomy regarding
The time of first rescue analgesia during the first 24 hours postoperatively
Intraoperative fentanyl consumption
Postoperative morphine consumption
Postoperative VAS scores
Intra postoperative complications of study drugs
Hypothesis
We assume that the combination of preoperative oral gabapentin and intraoperative IV dexmedetomidine infusion can provide more analgesic effect than either drug alone in the form of delaying first rescue analgesia time reducing the total amount of opioid consumption and improving postoperative VAS score
Ethical Considerations
This study will be conducted after the approval of the research committee of the department of anaesthesia surgical ICU and pain management in Kasr Alainy Hospital Cairo University and the ethical committee of the Faculty Of Medicine Cairo University Informed consent will be taken from all patients included in the study
Methodology
Patients will be assessed the day before surgery in a preoperative visit for evaluating their medical status laboratory investigations and for fulfilling all the above inclusion and exclusion criteria The patients will be instructed how to report pain using the visual analogue scale VAS score rating in which 0 no pain and 10 worst possible pain All groups of the study will be premedicated with IV 002 mgkg midazolam 30 minutes preoperatively Heart rate HR mean arterial blood pressure MBP will be monitored before the induction of anaesthesia baseline values immediately before surgical incision and at 15 min intervals intraoperatively Also the patients will be randomly assigned into three equal comparable groups each of which 30 patients using computer-generated random numbers
D group Patients will receive two oral placebo capsules starch capsules 1 hour before surgery and then will receive a loading dose of 1µgkg of dexmedetomidine made to 50 ml using normal saline and given intravenously just before induction of anaesthesia over 10 minutes while patient vital signs monitored followed by intravenous infusion of dexmedetomidine diluted in normal saline with a dose of 05µgkghour starts with induction of anaesthesia at a rate of 10 mlhour through identical syringe pump until skin closure
G group Patients will receive two oral gabapentin 300 mg capsules for a total of 600 mg gabapentin Neurontin Pfizer Cairo Egypt 1 hour before surgery and then will receive 50 ml of normal saline given intravenously just before induction of anaesthesia over 10 minutes while patient vital signs monitored followed by intravenous normal saline infusion intraoperatively starts with induction of anaesthesia at a rate of 10 mlhour through identical syringe pump until skin closure
DG group Patients will receive two gabapentin 300 mg capsules for a total of 600 mg gabapentin 1 hour before surgery and then will receive a loading dose of 1µgkg of dexmedetomidine made to 50 ml using normal saline and given intravenously just before induction of anaesthesia over 10 minutes while patient vital signs monitored followed by intravenous infusion of dexmedetomidine diluted in normal saline with a dose of 05µgkghour starts with induction of anaesthesia at a rate of 10 mlhour through identical syringe pump until skin closure
Dexmedetomidine or saline infusion loading started 10 minutes before the induction of anaesthesia while patient vital signs monitored and Maintenance started with induction of anaesthesia and continued until skin closure at the end of surgery
This study is a double-blind study so neither the participants nor the experimenters will know who is receiving a particular treatment The drugs will be prepared by an anaesthesiologist who has no further role in the study the doses of administered IV drugs will be calculated according to the patients body weight and they will be supplied as two syringes labelled respectively as loading syringes which will contain 50 ml of normal saline or a loading dose of dexmedetomidine made to 50 ml using normal saline and both will be given intravenously over 10 minutes just before induction of anaesthesia while patient vital signs monitored and Maintenance syringes that will contain normal saline or a maintenance dose of dexmedetomidine diluted in normal saline and both will be given intravenously with the induction of anaesthesia at a rate of 10 mlhour and continued until skin closure All syringes pump will be used in the study will be identical In addition to this both placebo capsules starch capsules and gabapentin capsules Neurontin 300mg will be identical-looking capsules yellow in colour and capsule in shape Also the surgical team the patients the anaesthesiologists and the investigators responsible for collecting intraoperative and postoperative recorded data did not know about the groups allocation
3 Anaesthesia Management
The patients included in the study will be kept fasting for at least six hours before surgery and will be monitored continuously using electrocardiography non-invasive blood pressure peripheral oxygen saturation and end-tidal carbon dioxide - using the Datex-Ohmeda S5 anaesthesia monitor model no USE1913A - throughout the surgical procedure The intravenous IV access will be secured using a 20 gauge G cannula for IV fluid management and another IV access for the infusion of the study drugs
Induction of general anaesthesia in all study groups will be performed using a regimen of IV 2 μcgkg fentanyl and propofol IV 2 mg kg Tracheal intubation will be facilitated using 05 mgkg IV of Atracurium Anaesthesia will be maintained with inhaled sevoflurane in oxygen-enriched air FiO 205 and top-up doses of atracurium 01 mgkg IV will be administered as required guided by a nerve stimulator All patients will be mechanically ventilated aiming to keep end-tidal carbon dioxide within the range of 30-35 mmHg All patients will receive 1 g of IV paracetamol The total intraoperative fentanyl consumption will be recorded in all study groups Bispectral index BIS will be used for monitoring the depth of anaesthesia with target BIS values from 40 to 60 because all the study drugs have a synergistic effect with inhaled anaesthesia
Ringer acetate will be infused to replace any fluid deficit maintenance and losses Hypotension will be defined as MBP less than 60mmHg or less than 70 from baseline episodes of hypotension will be treated with ringer acetate boluses andor 5mg ephedrine in incremental doses to maintain mean blood pressure above 70 mmHg Additional bolus doses of fentanyl 05µgkg will be given if the mean blood pressure or heart rate rises above 20 of baseline values
At the end of the surgery the residual neuromuscular blockade will be reversed using neostigmine 005 mgkg and atropine 002 mgkg and extubation will be performed after complete recovery of the airway reflexes The patients will be transferred to the post-anaesthesia care unit then according to the modified Aldrete discharge scale the patients will be shifted to the ward when the patient achieves an Aldrete score of 910¹⁶ MBP heart rate and VAS pain score will be noted immediately on arrival in the post-anaesthesia care unit and at 2 6 12 18 and 24 h postoperatively All patients will be given paracetamol postoperatively 1 g IV every 8 hours until discharged Rescue analgesia will be provided in the form of IV morphine 3 mg boluses if the pain score was 3 with a maximum allowed daily dose of 05 mgkg24 hours The time of the first rescue analgesia and the total amount of morphine given in the first 24 hours postoperatively will be recorded in the three groups
Side effects such as nausea vomiting sedation hallucination respiratory depression respiratory rate 10min Postoperative nausea and vomiting PONV as side effects of morphine will be recorded upon arrival to PACU and at 2 6 12 18 and 24 h postoperatively on a four-point verbal scale¹⁷ none no nausea mild nausea but no vomiting moderate vomiting one attack severe vomiting one attack 01 mgkg of IV ondansetron will be given to patients with moderate or severe postoperative nausea and vomiting
Sedation will be assessed and scored at the same times of assessment of VAS of pain at 2 6 12 18 and 24 h postoperatively and in the recovery room with Ramsay scores¹⁸ 1 anxious or restless or both 2 cooperative orientated and tranquil 3 responding to commands 4 brisk response to a stimulus 5 sluggish response to a stimulus and 6 no response to stimulus excessively high Sedation level with Ramsay 5 or 6 adequate sedation levels needing observation with Ramsay 2 to 4 and inadequate or insufficient sedation level with Ramsay 1
Statistical Methods
Sample size justification
The aim of this study is to compare the analgesic effects of perioperative IV infusion of dexmedetomidine and preoperative oral gabapentin in patients undergoing modified radical mastectomy surgery Based on the previous work by Grover et al 2009¹⁹ who reported the mean duration time of first rescue analgesia was 90611 minutes and Alzeftawy Elsheikh 2015²⁰ who reported 125 257 minutes for Dexmedetomidine infusion Using power 80 and 5 significance level 30 patients in every group will be required The sample size is calculated using GPower program²¹ University of Düsseldorf Düsseldorf Germany
Statistical analysis
Data will be analyzed using IBM SPSS advanced statistics Statistical Package for Social Sciences version 24 SPSS Inc Chicago IL Numerical data will be described as mean and standard deviation or median and range Data will be explored for normality using Kolmogrov-Smirnov test and Shapiro-Wilk test Comparisons between 3 groups for normally distributed numeric variables will be done using the ANOVA while for non normally distributed numeric variables will be done by Kruskal Wallis test A p-value less than or equal to 005 will be considered statistically significant All tests will be two tailed
Categorical data will be described as numbers and percentages and comparisons will be done by chi square test or fisher exact as appropriate
Breast cancer is the most common malignant tumour among females with an incidence of about 21 million women every year It is the greatest cancer-related mortality among women approximately 15 of all cancer mortality In addition to that Egypt follows the international incidence with breast cancer being the most common malignancy among females with 18660 patients each year¹ Modified Radical Mastectomy MRM is one of the main surgical treatments of breast cancer Accordingly it is an account for 31 of all breast surgery cases² The common modality for anaesthesia for MRM is general anaesthesia with or without regional blocks³
Nearly about 40-60 of breast surgery patients develop severe acute postoperative pain⁴ Opioids are the current best standard drugs for postoperative pain relief however exposure to large doses of opioids leads to multiple side effects like prolonged sedation respiratory depression nausea and vomiting⁵ Moreover the use of opioids inhibits cell-mediated immunity with an increase in tumour angiogenesis cell migration and metastasis in addition to the progression of the cell cycle Therefore plans other than opioids are recommended without losing proper and effective analgesia especially in breast cancer patients who are more sensitive to develop opioid tolerance and addiction⁶ So it became a necessity to find safe analgesic techniques for these patients by using different techniques like adjuvant therapies or multimodal analgesia by combining different drugs with different mechanisms of action together to increase the quality of postoperative analgesia and to decrease the need for high doses of systemic opioids and their related side addiction⁷⁸
Alpha-2 agonists including clonidine and dexmedetomidine have been used perioperatively Dexmedetomidine is different from clonidine in two properties It has more affinity for the alpha-2 receptor 8 times that of clonidine and is easier to titrate⁹ Also dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has sedative analgesic anaesthetic-sparing properties without causing any respiratory depression¹⁰ Dexmedetomidine can be a good anaesthetic premedication because of its sympatholytic effect to attenuate the sympathetic stress response to perioperative stresses like laryngoscopy and intubation¹¹ The analgesic effect provided by dexmedetomidine is mediated mainly through interaction at alpha-2a within the spinal cord where drug activity attenuates nociceptive signal transduction And although dexmedetomidine when given alone has been documented to reduce pain it has a synergistic or additive effect when combined with opioids¹²
Another promising drug for postoperative pain management is gabapentin It binds to the α-2 δ subunit of voltage-gated calcium channels and preventing the release of nociceptive neurotransmitters like glutamate substance P and noradrenaline¹³ Evidence suggests that in addition to its effectiveness as an analgesic for patients with neuropathic pain and chronic pain syndromes gabapentin also provides effective postoperative analgesia when given before an operation¹⁴¹⁵ Therefore the combination of IV dexmedetomidine and oral gabapentin due to their analgesic effects would be more effective in reducing postoperative analgesic consumption and providing prolonged postoperative analgesia after a modified radical mastectomy
To the best of researchers knowledge comparing the effect of perioperative intravenous dexmedetomidine infusion preoperative oral gabapentin and their combination on the total consumption of intraoperative and postoperative opioids in patients undergoing modified radical mastectomy was not investigated before
Aim of the work
This work is a comparative study that aims to compare the analgesic effects of perioperative IV infusion of dexmedetomidine preoperative oral gabapentin and their combination in patients undergoing modified radical mastectomy surgery regarding the time of first rescue analgesia postoperative morphine consumption and possible complications
Objectives
To assess the analgesic outcomes of perioperative IV infusion of dexmedetomidine preoperative oral gabapentin and their combination in controlling acute postoperative pain in modified radical mastectomy regarding
The time of first rescue analgesia during the first 24 hours postoperatively
Intraoperative fentanyl consumption
Postoperative morphine consumption
Postoperative VAS scores
Intra postoperative complications of study drugs
Hypothesis
We assume that the combination of preoperative oral gabapentin and intraoperative IV dexmedetomidine infusion can provide more analgesic effect than either drug alone in the form of delaying first rescue analgesia time reducing the total amount of opioid consumption and improving postoperative VAS score
Ethical Considerations
This study will be conducted after the approval of the research committee of the department of anaesthesia surgical ICU and pain management in Kasr Alainy Hospital Cairo University and the ethical committee of the Faculty Of Medicine Cairo University Informed consent will be taken from all patients included in the study
Methodology
Patients will be assessed the day before surgery in a preoperative visit for evaluating their medical status laboratory investigations and for fulfilling all the above inclusion and exclusion criteria The patients will be instructed how to report pain using the visual analogue scale VAS score rating in which 0 no pain and 10 worst possible pain All groups of the study will be premedicated with IV 002 mgkg midazolam 30 minutes preoperatively Heart rate HR mean arterial blood pressure MBP will be monitored before the induction of anaesthesia baseline values immediately before surgical incision and at 15 min intervals intraoperatively Also the patients will be randomly assigned into three equal comparable groups each of which 30 patients using computer-generated random numbers
D group Patients will receive two oral placebo capsules starch capsules 1 hour before surgery and then will receive a loading dose of 1µgkg of dexmedetomidine made to 50 ml using normal saline and given intravenously just before induction of anaesthesia over 10 minutes while patient vital signs monitored followed by intravenous infusion of dexmedetomidine diluted in normal saline with a dose of 05µgkghour starts with induction of anaesthesia at a rate of 10 mlhour through identical syringe pump until skin closure
G group Patients will receive two oral gabapentin 300 mg capsules for a total of 600 mg gabapentin Neurontin Pfizer Cairo Egypt 1 hour before surgery and then will receive 50 ml of normal saline given intravenously just before induction of anaesthesia over 10 minutes while patient vital signs monitored followed by intravenous normal saline infusion intraoperatively starts with induction of anaesthesia at a rate of 10 mlhour through identical syringe pump until skin closure
DG group Patients will receive two gabapentin 300 mg capsules for a total of 600 mg gabapentin 1 hour before surgery and then will receive a loading dose of 1µgkg of dexmedetomidine made to 50 ml using normal saline and given intravenously just before induction of anaesthesia over 10 minutes while patient vital signs monitored followed by intravenous infusion of dexmedetomidine diluted in normal saline with a dose of 05µgkghour starts with induction of anaesthesia at a rate of 10 mlhour through identical syringe pump until skin closure
Dexmedetomidine or saline infusion loading started 10 minutes before the induction of anaesthesia while patient vital signs monitored and Maintenance started with induction of anaesthesia and continued until skin closure at the end of surgery
This study is a double-blind study so neither the participants nor the experimenters will know who is receiving a particular treatment The drugs will be prepared by an anaesthesiologist who has no further role in the study the doses of administered IV drugs will be calculated according to the patients body weight and they will be supplied as two syringes labelled respectively as loading syringes which will contain 50 ml of normal saline or a loading dose of dexmedetomidine made to 50 ml using normal saline and both will be given intravenously over 10 minutes just before induction of anaesthesia while patient vital signs monitored and Maintenance syringes that will contain normal saline or a maintenance dose of dexmedetomidine diluted in normal saline and both will be given intravenously with the induction of anaesthesia at a rate of 10 mlhour and continued until skin closure All syringes pump will be used in the study will be identical In addition to this both placebo capsules starch capsules and gabapentin capsules Neurontin 300mg will be identical-looking capsules yellow in colour and capsule in shape Also the surgical team the patients the anaesthesiologists and the investigators responsible for collecting intraoperative and postoperative recorded data did not know about the groups allocation
3 Anaesthesia Management
The patients included in the study will be kept fasting for at least six hours before surgery and will be monitored continuously using electrocardiography non-invasive blood pressure peripheral oxygen saturation and end-tidal carbon dioxide - using the Datex-Ohmeda S5 anaesthesia monitor model no USE1913A - throughout the surgical procedure The intravenous IV access will be secured using a 20 gauge G cannula for IV fluid management and another IV access for the infusion of the study drugs
Induction of general anaesthesia in all study groups will be performed using a regimen of IV 2 μcgkg fentanyl and propofol IV 2 mg kg Tracheal intubation will be facilitated using 05 mgkg IV of Atracurium Anaesthesia will be maintained with inhaled sevoflurane in oxygen-enriched air FiO 205 and top-up doses of atracurium 01 mgkg IV will be administered as required guided by a nerve stimulator All patients will be mechanically ventilated aiming to keep end-tidal carbon dioxide within the range of 30-35 mmHg All patients will receive 1 g of IV paracetamol The total intraoperative fentanyl consumption will be recorded in all study groups Bispectral index BIS will be used for monitoring the depth of anaesthesia with target BIS values from 40 to 60 because all the study drugs have a synergistic effect with inhaled anaesthesia
Ringer acetate will be infused to replace any fluid deficit maintenance and losses Hypotension will be defined as MBP less than 60mmHg or less than 70 from baseline episodes of hypotension will be treated with ringer acetate boluses andor 5mg ephedrine in incremental doses to maintain mean blood pressure above 70 mmHg Additional bolus doses of fentanyl 05µgkg will be given if the mean blood pressure or heart rate rises above 20 of baseline values
At the end of the surgery the residual neuromuscular blockade will be reversed using neostigmine 005 mgkg and atropine 002 mgkg and extubation will be performed after complete recovery of the airway reflexes The patients will be transferred to the post-anaesthesia care unit then according to the modified Aldrete discharge scale the patients will be shifted to the ward when the patient achieves an Aldrete score of 910¹⁶ MBP heart rate and VAS pain score will be noted immediately on arrival in the post-anaesthesia care unit and at 2 6 12 18 and 24 h postoperatively All patients will be given paracetamol postoperatively 1 g IV every 8 hours until discharged Rescue analgesia will be provided in the form of IV morphine 3 mg boluses if the pain score was 3 with a maximum allowed daily dose of 05 mgkg24 hours The time of the first rescue analgesia and the total amount of morphine given in the first 24 hours postoperatively will be recorded in the three groups
Side effects such as nausea vomiting sedation hallucination respiratory depression respiratory rate 10min Postoperative nausea and vomiting PONV as side effects of morphine will be recorded upon arrival to PACU and at 2 6 12 18 and 24 h postoperatively on a four-point verbal scale¹⁷ none no nausea mild nausea but no vomiting moderate vomiting one attack severe vomiting one attack 01 mgkg of IV ondansetron will be given to patients with moderate or severe postoperative nausea and vomiting
Sedation will be assessed and scored at the same times of assessment of VAS of pain at 2 6 12 18 and 24 h postoperatively and in the recovery room with Ramsay scores¹⁸ 1 anxious or restless or both 2 cooperative orientated and tranquil 3 responding to commands 4 brisk response to a stimulus 5 sluggish response to a stimulus and 6 no response to stimulus excessively high Sedation level with Ramsay 5 or 6 adequate sedation levels needing observation with Ramsay 2 to 4 and inadequate or insufficient sedation level with Ramsay 1
Statistical Methods
Sample size justification
The aim of this study is to compare the analgesic effects of perioperative IV infusion of dexmedetomidine and preoperative oral gabapentin in patients undergoing modified radical mastectomy surgery Based on the previous work by Grover et al 2009¹⁹ who reported the mean duration time of first rescue analgesia was 90611 minutes and Alzeftawy Elsheikh 2015²⁰ who reported 125 257 minutes for Dexmedetomidine infusion Using power 80 and 5 significance level 30 patients in every group will be required The sample size is calculated using GPower program²¹ University of Düsseldorf Düsseldorf Germany
Statistical analysis
Data will be analyzed using IBM SPSS advanced statistics Statistical Package for Social Sciences version 24 SPSS Inc Chicago IL Numerical data will be described as mean and standard deviation or median and range Data will be explored for normality using Kolmogrov-Smirnov test and Shapiro-Wilk test Comparisons between 3 groups for normally distributed numeric variables will be done using the ANOVA while for non normally distributed numeric variables will be done by Kruskal Wallis test A p-value less than or equal to 005 will be considered statistically significant All tests will be two tailed
Categorical data will be described as numbers and percentages and comparisons will be done by chi square test or fisher exact as appropriate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None