Malignant Neoplasms of Digestive Organs, Malignant Neoplasms of Female Genital Organs, Malignant Neoplasms of Male Genital Organs, Malignant Neoplasms of Urinary Tract
Conditions
Keywords
Malignant neoplasms of digestive organs, Malignant neoplasms of female genital organs, Malignant neoplasms of male genital organs, Malignant neoplasms of urinary tract, Neuromuscular blockade, NMB, Sugammadex, Neostigmine, Pain Assessment, Survey
Brief summary
Insufflation pressure (IP) is the creation of a pressure barrier of air/gas within the abdomen to allow the surgeon more space to work during abdominal surgery. Shoulder pain is a common complaint from patients who have had abdominal surgery and the pain is thought to be related to the use of IP. In addition to anesthesia (which keeps you asleep during surgery), the current standard practice is to block the nerve-muscle junction with a type of drug called neuromuscular blockade (NMB) which paralyzes the abdominal muscles. This means that a lower level of insufflation pressure is needed by the surgeon. To reverse the effects of NMB after surgery, a drug called neostigmine is given. The goal of this clinical research study is to compare the use of standard-of-care moderate NMB and neostigmine to the use of deep NMB and a drug called Sugammadex when given to elderly patients (patients who are 65 years of age or older) who are scheduled to have robotic abdominal surgery. Deep and moderate in this study refers to the dose or strength of the NMB given. This is an investigational study. Sugammadex and neostigmine are FDA approved and commercially available for the reversal of NMB. It is considered investigational to compare Sugammadex and neostigmine to learn if the use of one or the other in elderly patients can reduce the level of shoulder pain after surgery. Up to 100 participants will be enrolled in this study. All will take part at MD Anderson.
Detailed description
Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups before your surgery. This is done because no one knows if one group is better, the same, or worse than the other. * In Group 1, you will receive deep NMB and Sugammadex. * In Group 2, you will receive moderate NMB and neostigmine. Neither you nor the surgeon or surgical staff will know to which group you have been assigned. The surgeon will not know which group you are in because researchers want to learn how much, if at all, the surgeon needs to adjust the insufflation pressure during surgery. However, if needed for your safety, the surgeon will be able to find out which group you are in. For your safety, the anesthesiologist will know to which group you have been assigned. Surgery and Study Drug Administration: After you have been assigned to a study group, you will have your surgery as scheduled. You will sign a separate consent form for surgery which describes the procedure and its risks in more detail. You will also sign a separate consent form to receive anesthesia. Before your surgery, blood (about 2 teaspoons) will be drawn for biomarker testing. Biomarkers are found in the blood/tissue and may be related to the status of the disease and/or your reaction to the study drug(s). During the surgery, the insufflation pressure that is being used, including any changes that are made to the pressure, will be recorded. After the surgery has been completed, you will receive either Sugammadex or neostigmine by vein until the effects of the NMB have been reversed. You will recover after surgery in the post-anesthesia care unit (PACU). At about 15, 45, and 90 minutes after your surgery, a PACU nurse will ask you about any shoulder pain you are feeling and if so, how intense the pain is. Information about how long you stay in the hospital after surgery and if you have any side effects after surgery (such as nausea/vomiting or shoulder pain) will also be collected from your medical record. Follow-Up: After 30 days after you leave the hospital, you will be called by a member of the study staff to ask how you are doing and if you have had any additional hospitalizations since leaving the hospital. This phone call should last about 5-10 minutes. Length of Study Participation: Your participation in this study will be over after completing the 30-day follow up phone call.
Interventions
Deep Neuromuscular Blockade (NMB) given during surgery.
Moderate Neuromuscular Blockade (NMB) given during surgery.
DRUGSugammadex
4 mg/Kg, intravenously as a single bolus injection after surgery.
DRUGNeostigmine
70 mcg/Kg up to a total of 5 mg, intravenously slowly over a period of at least 1 minute after surgery.
BEHAVIORALPain Assessment
Pain assessment done at about 15, 45, and 90 minutes after surgery.
Sponsors
Merck Sharp & Dohme LLC
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients 65 years of age or older 2. Patients having robotic prostatectomy 3. Written informed consent
Exclusion criteria
1. Patient with known hypersensitivity to Rocuronium, Sugammadex or its components 2. Patients with severe renal insufficiency, defined and confirmed by an estimated creatinine clearance equal or lower than 30 mL/min, per institutional laboratory. 3. Patients with history of severe liver disease, defined as and confirmed by elevated ALT and AST greater than 1.5 times the Upper Limit of Normal along with Albumin less than 3 OR INR 1.5 or greater per institutional laboratory.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Reported Shoulder Pain | 30 days | Visual Analog Scale (VAS) pain score (0-10) for shoulder pain recorded, where 0 means no pain and 10 means the worst pain ever experienced . Percentage of participants who experienced should pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Muscle Response Using Train-of-Four (TOF) in Post-Anesthesia Care Unit (PACU) to Measure Residual Muscle Relaxation | Day 0 - Arrival time at PACU, an average of 3 minutes | The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the DNMB group, the rate will be adjusted and boluses given to maintain 1-2 post tetanic responses during the pneumoperitoneum. NMB will be reversed with Sugammadex 4 mg/Kg, intravenously as a single bolus injection, at the end of the surgery. Percentage of measured contraction strength of the fourth stimulus compared to the first stimulus. |
| Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | Assessed at 15, 45, 90 minutes during PACU stay. | Determined by the Dansk Selskab for Anæstesiologi og Intensiv Medicin(DASAIM)discharge criteria.Pts considered ready to discharge when the sum of all categories is\<4 and no single category has a score of \>1.Sedation.0:Patient is fully awake.1: Patient is asleep,aroused by verbal stimulation.2:Patient is asleep, aroused by physical stimulation.3:Patient is asleep,cannot be aroused.Respiratory Rate.0:Respiratory rate\>10. 1: Snoring,10\< RR\<30. 2:R\<10 or RR\>30/min.3:Periods of apnea or obstructive patterns.Oxygen Saturation.0:SpO2 ≥ 94%.1:90%≤SpO2\<94%. 2:85%≤ SpO2 \< 90%.3:SpO2 \< 85%. Systolic Blood Pressure. 0:SBP ≥ 100mmHg.1:90mmHg≤SBP\< 100mmHg.2:80mmHg≤SBP\< 90mmHg or SBP\>220mmHg.3:SBP\<80mmHg.Heart Rate.0:50\<HR≤100.1:100\<HR≤120.2:40\<HR≤ 50 or 120\<HR≤130.3:HR\<40 or HR\>130.Pain at rest.0:No pain 1:Light pain.2:Moderate pain.3:Severe pain.Nausea.0:No nausea or vomiting.1:Light nausea or vomiting without previous nausea. 2:Moderate nausea and/or vomiting.3:Severe nausea and/or vomiting. |
| Cumulative Intraoperative Insufflation Pressure | Day 0 - IntraOperative-From beginning of pneumoperitoneum to desufflation (an average of 166 minutes) | Intra-abdominal insufflation time and pressure directed by the surgeon and recorded continuously by the clinical coordinator until the time of desufflation. |
| Surgical Exposure Grading | Day 0 - IntraOperative, from incision time to closing time(average 190 minutes) | — |
| Length of Hospital Stay | length of hospital stay(average of 3 days) | — |
| Percentage of Participants With Nausea and/or Vomiting in PACU | Day 0 - PACU stay, an average of 120 minutes | Degree of Post-Operative Nausea determined per Visual Analog Scale per nurse in Post-Anesthesia Care Unit (PACU). |
Countries
United States
Participant flow
Recruitment details
Patients were identified when scheduled for Robotic Prostatectomy. Eligible subjects were approached before scheduled surgery to obtain Informed Consent. Patients were recruited from November, 2017 through July, 2018.
Participants by arm
| Arm | Count |
|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the DNMB group, the rate will be adjusted and boluses given to maintain 1-2 post tetanic responses during the pneumoperitoneum. NMB will be reversed with Sugammadex 4 mg/Kg, intravenously as a single bolus injection, at the end of the surgery. | 50 |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the MNMB group, the Rocuronium infusion rate will be adjusted to maintain 1-2 TOF responses and will be reversed with Neostigmine 70 mcg/Kg up to a total of 5 mg, intravenously slowly over a period of at least 1 minute, at the end of surgery. | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Deep Neuromuscular Blockade (NMB) + Sugammadex | Moderate Neuromuscular Blockade (NMB) + Neostigmine | Total |
|---|---|---|---|
| Adjuvant or Immunotherapy | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 44 Participants | 43 Participants | 87 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Continuous | 69.12 years STANDARD_DEVIATION 3.6289 | 69.26 years STANDARD_DEVIATION 3.6073 | 69.19 years STANDARD_DEVIATION 3.6 |
| Body mass index (BMI) | 29.044 kg/m^2 STANDARD_DEVIATION 4.8 | 28.662 kg/m^2 STANDARD_DEVIATION 3.9567 | 28.85 kg/m^2 STANDARD_DEVIATION 4.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 42 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 39 Participants | 79 Participants |
| Region of Enrollment United States | 50 participants | 50 participants | 100 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 50 Participants | 50 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 13 / 50 | 15 / 50 |
| serious Total, serious adverse events | 3 / 50 | 2 / 50 |
Outcome results
Primary
Percentage of Patients Who Reported Shoulder Pain
Visual Analog Scale (VAS) pain score (0-10) for shoulder pain recorded, where 0 means no pain and 10 means the worst pain ever experienced . Percentage of participants who experienced should pain.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Percentage of Patients Who Reported Shoulder Pain | 12 percentage of participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Percentage of Patients Who Reported Shoulder Pain | 10 percentage of participants |
Secondary
Cumulative Intraoperative Insufflation Pressure
Intra-abdominal insufflation time and pressure directed by the surgeon and recorded continuously by the clinical coordinator until the time of desufflation.
Time frame: Day 0 - IntraOperative-From beginning of pneumoperitoneum to desufflation (an average of 166 minutes)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Cumulative Intraoperative Insufflation Pressure | 1995 mmHg |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Cumulative Intraoperative Insufflation Pressure | 1581 mmHg |
Secondary
Length of Hospital Stay
Time frame: length of hospital stay(average of 3 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Length of Hospital Stay | 2.2323 days | Standard Deviation 2.0859 |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Length of Hospital Stay | 1.8623 days | Standard Deviation 1.0545 |
Secondary
Percentage of Muscle Response Using Train-of-Four (TOF) in Post-Anesthesia Care Unit (PACU) to Measure Residual Muscle Relaxation
The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the DNMB group, the rate will be adjusted and boluses given to maintain 1-2 post tetanic responses during the pneumoperitoneum. NMB will be reversed with Sugammadex 4 mg/Kg, intravenously as a single bolus injection, at the end of the surgery. Percentage of measured contraction strength of the fourth stimulus compared to the first stimulus.
Time frame: Day 0 - Arrival time at PACU, an average of 3 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Percentage of Muscle Response Using Train-of-Four (TOF) in Post-Anesthesia Care Unit (PACU) to Measure Residual Muscle Relaxation | 110 Percentage of measured contraction |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Percentage of Muscle Response Using Train-of-Four (TOF) in Post-Anesthesia Care Unit (PACU) to Measure Residual Muscle Relaxation | 100 Percentage of measured contraction |
Secondary
Percentage of Participants With Nausea and/or Vomiting in PACU
Degree of Post-Operative Nausea determined per Visual Analog Scale per nurse in Post-Anesthesia Care Unit (PACU).
Time frame: Day 0 - PACU stay, an average of 120 minutes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Percentage of Participants With Nausea and/or Vomiting in PACU | Nausea | 7 percentage of participants |
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Percentage of Participants With Nausea and/or Vomiting in PACU | Vomiting | 1 percentage of participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Percentage of Participants With Nausea and/or Vomiting in PACU | Nausea | 6 percentage of participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Percentage of Participants With Nausea and/or Vomiting in PACU | Vomiting | 0 percentage of participants |
Secondary
Readiness to Discharge From the Post-Anesthesia Care Unit (PACU)
Determined by the Dansk Selskab for Anæstesiologi og Intensiv Medicin(DASAIM)discharge criteria.Pts considered ready to discharge when the sum of all categories is\<4 and no single category has a score of \>1.Sedation.0:Patient is fully awake.1: Patient is asleep,aroused by verbal stimulation.2:Patient is asleep, aroused by physical stimulation.3:Patient is asleep,cannot be aroused.Respiratory Rate.0:Respiratory rate\>10. 1: Snoring,10\< RR\<30. 2:R\<10 or RR\>30/min.3:Periods of apnea or obstructive patterns.Oxygen Saturation.0:SpO2 ≥ 94%.1:90%≤SpO2\<94%. 2:85%≤ SpO2 \< 90%.3:SpO2 \< 85%. Systolic Blood Pressure. 0:SBP ≥ 100mmHg.1:90mmHg≤SBP\< 100mmHg.2:80mmHg≤SBP\< 90mmHg or SBP\>220mmHg.3:SBP\<80mmHg.Heart Rate.0:50\<HR≤100.1:100\<HR≤120.2:40\<HR≤ 50 or 120\<HR≤130.3:HR\<40 or HR\>130.Pain at rest.0:No pain 1:Light pain.2:Moderate pain.3:Severe pain.Nausea.0:No nausea or vomiting.1:Light nausea or vomiting without previous nausea. 2:Moderate nausea and/or vomiting.3:Severe nausea and/or vomiting.
Time frame: Assessed at 15, 45, 90 minutes during PACU stay.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | DASAIM at 15 min | 2.92 Score on a scale | Standard Deviation 1.6393 |
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | DASAIM at 45 min | 2.82 Score on a scale | Standard Deviation 1.6744 |
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | DASAIM at 90 min | 2.12 Score on a scale | Standard Deviation 1.599 |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | DASAIM at 15 min | 3.16 Score on a scale | Standard Deviation 1.6946 |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | DASAIM at 45 min | 2.86 Score on a scale | Standard Deviation 1.6904 |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Readiness to Discharge From the Post-Anesthesia Care Unit (PACU) | DASAIM at 90 min | 1.8 Score on a scale | Standard Deviation 1.4286 |
Secondary
Surgical Exposure Grading
Time frame: Day 0 - IntraOperative, from incision time to closing time(average 190 minutes)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Surgical Exposure Grading | Optimal | 25 Participants |
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Surgical Exposure Grading | Acceptable | 5 Participants |
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Surgical Exposure Grading | Good | 19 Participants |
| Deep Neuromuscular Blockade (NMB) + Sugammadex | Surgical Exposure Grading | Poor | 1 Participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Surgical Exposure Grading | Good | 8 Participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Surgical Exposure Grading | Optimal | 33 Participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Surgical Exposure Grading | Poor | 1 Participants |
| Moderate Neuromuscular Blockade (NMB) + Neostigmine | Surgical Exposure Grading | Acceptable | 8 Participants |