Trial Comparing Intrathecal Morphine With Placebo In Patients Undergoing Robotic Cardiac Surgery

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT03241485
• Collaborator: (none)
• Enrollment: 79
• Location: 1
• Arms: 2
• Actual Duration (Months): 26.4
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This is a randomized clinical trial in patients undergoing robotic myocardial revascularization with intraoperative extubation. Patients will be randomized into placebo or intrathecal morphine groups to assess postoperative pain scores and patient satisfaction. Patients will also be assessed for side effects from the intervention.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Intrathecal morphine; Drug: Placebo	Phase 4

Detailed Description

Following Institutional Review Board approval and informed patient consent, 120 patients scheduled for elective robotic myocardial revascularization without cardiopulmonary bypass and anticipated intraoperative tracheal extubation will be studied. Patients will be randomized into one of two groups. Group A (placebo, control group) will receive intrathecal normal saline, Group B (morphine group) intrathecal morphine. All procedures will occur and administered medications given immediately prior to induction of general anesthesia in the operating room. Power analysis indicates that 60 patients per Group is appropriate, as further described below. Inclusion criteria include any patient undergoing elective robotic myocardial revascularization without anticipated use of cardiopulmonary bypass and with anticipated intraoperative tracheal extubation. Exclusion criteria include emergency surgery, ejection fraction less than 40%, preoperative use of inotropic agents or intraaortic balloon pump, anticipated use of cardiopulmonary bypass, previous cardiothoracic surgery, anticipated postoperative tracheal intubation, severe pulmonary disease, morbid obesity (BMI >35 kg/m2), severe renal dysfunction (creatinine > 1.5) recent history of opioid abuse, preoperative use of opioids, or any contraindication to intrathecal injection (patient refusal, difficult patient anatomy, pre-existing coagulopathy, morphine allergy).

Routine preoperative data will be collected (see Preoperative Data Sheet). Following intravenous access and routine mild sedation, each patient will be transported to the operating room and assume the sitting position. Following routine skin preparation, a routine lumbar intrathecal injection will be made via a 22-g spinal needle. The injectate will be either morphine (5 mcg/kg, maximum dose of 1 mg) or normal saline. The injectate will be prepared by a co-Investigator not directly involved in patient care. Thus, all preoperative, intraoperative, and postoperative caregivers will be blinded to intrathecal injectate composition (all injectates will be standardized to a total of 1.0 ml). All patients will have port incisions injected with 60 ml of 0.25% bupivacaine by the surgeon after the completion of surgery.

Following intrathecal injection, the patient will then assume the supine position. An arterial catheter will be inserted and general endotracheal anesthesia will be induced. Intraoperative anesthetic technique will be standardized and equivalent between Groups (see Intraoperative Anesthetic Protocol Sheet). The anesthetic protocol will allow tracheal extubation to occur in the operating room immediately after surgery (if clinically indicated).

Surgical technique will not be altered in any way. All patients in both Groups will be operated on by the same surgeon. Routine intraoperative data will be collected (see Intraoperative Data Sheet). In all patients, tracheal extubation will be attempted in the operating room immediately after surgery (if clinically indicated).

Both Groups will receive routine postoperative care and identical postoperative analgesic protocols to assess adequacy of postoperative analgesia (see Postoperative Analgesia Protocol and Postoperative Data Sheets). The American Pain Society Outcome Questionnaire (APS-POQ) will be administered to patients prior to discharge (see data sheet).15

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The patients will be randomized into 2 groups. The placebo group will receive intrathecal saline. The morphine group will receive intrathecal morphine.The patients will be randomized into 2 groups. The placebo group will receive intrathecal saline. The morphine group will receive intrathecal morphine.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: All patients will receive intrathecal intervention and will not know which group they are assigned to. The provider performing the procedure and collecting the data will also be blinded to the intervention assignment.
• Primary Purpose: Treatment
• Official Title: Randomized, Double Blinded, Trial Comparing Intrathecal Morphine With Placebo in Patients Undergoing Robotic Totally Endoscopic Beating Heart Coronary Revascularization and Intraoperative Extubation
• Actual Study Start Date: Jun 19, 2018
• Actual Primary Completion Date: Sep 1, 2020
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 60 patients will be randomly assigned to this arm. The patients in this arm will receive intrathecal saline.	Drug: Placebo; Saline intrathecal given in the same manner as the intervention groups.
Active Comparator: Intrathecal morphine 60 patients will be randomly assigned to this arm. The patients in this arm will receive intrathecal morphine.	Drug: Intrathecal morphine; 5 micrograms/kilogram of intrathecal morphine administered in the spinal space, not to exceed 1mg; Other Names: Duramorph

Outcome Measures

Primary Outcome Measures

1. Postoperative Morphine Consumption [24 hours after surgery]

   We anticipate that patients in the intervention groups will require less postoperative morphine for pain control.

Secondary Outcome Measures

1. Pain Score [First 48 hours after surgery]

   Patients will score their pain on a visual analog scale of 0-10. The higher the score, the worse the patients reported pain is at that time .

2. Patient Satisfaction [1-3 days after surgery, prior to discharge.]

   Patients will take a satisfaction survey prior to discharge, this is measured by calculating a score on a scale. This survey consist of questions that asks about the subjects post-operative experience with pain. Higher reported scores represent worse post-operative subject experience. These are ranked from a 0-10 scale, where 0 is the best experience and 10 meaning the worst experience. Questions being asked how satisfied they were with the results of the pain treatment while hospitalized, least pain in prior 24 hours, worst pain in prior 24 ours, percent time in severe pain, how much pain interfered with different activities, how much pain caused anxiety, depression, fright, helplessness, how severe were symptoms of nausea, drowsiness, itching, dizziness, and percentage pain relief in prior 24 hours.

3. Number of Participants With Nausea [Until discharge, 2-3 days after surgery]

   Daily evaluation of nausea post-operatively throughout the subjects hospital stay.

4. Number of Participants With Respiratory Depression [During hospital stay]

   Opioid related respiratory depression, post-operatively throughout the subjects hospital stay.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• patient undergoing elective robotic myocardial revascularization without anticipated use of cardiopulmonary bypass and with anticipated intraoperative tracheal extubation.

Exclusion Criteria:

• Emergency surgery

• Preoperative use of inotropes/IABP

• Preoperative use of opoids

• Ejection fraction less than 40%

• Anticipated use of cardiopulmonary bypass

• Previous cardiothoracic surgery

• Anticipated postoperative tracheal intubation

• severe pulmonary disease

• morbid obesity (BMI >35 kg/m2)

• severe hepatic impairment

• severe renal dysfunction (creatinine > 1.5)

• any contraindication to intrathecal injection (patient refusal, difficult patient anatomy, pre-existing coagulopathy, morphine allergy)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Hospital	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Richa Dhawan, MD, MPH, University of Chicago Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 26, 2019

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT03241485
• Other Study ID Numbers: IRB17-1103
• First Posted: Aug 7, 2017
• Last Update Posted: Nov 23, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Morphine

Study Results

Participant Flow

Arm/Group Title	Placebo	Intrathecal Morphine
Arm/Group Description	42 patients were randomized to the intrathecal placebo group. This group received a normal saline injected in the spinal spice, prior to surgery.	37 patients were randomized to the intrathecal morphine group. This group received 5 micrograms/kilogram of intrathecal morphine administered in the spinal space
Period Title: Overall Study
STARTED	42	37
COMPLETED	37	33
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Placebo	Intrathecal Morphine	Total
Arm/Group Description	42 patients were randomized to this group	37 patients were randomized to this group	Total of all reporting groups
Overall Participants	42	37	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (10)	67.3 (10.5)	65.8 (10.2)
Sex: Female, Male (Count of Participants)
Female	9 21.4%	5 13.5%	14 17.7%
Male	33 78.6%	32 86.5%	65 82.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Weight (KG) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [KG]	87 (14)	85 (14)	86.4 (14.2)
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	28.6 (3.6)	27.5 (3.2)	28 (3.3)
ASA Physical Status (Units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Units on a scale]	3	3	3
EuroSCORE II (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	1 (0.5)	1 (0.5)	1 (0.5)

Outcome Measures

1. Primary Outcome

Title	Postoperative Morphine Consumption
Description	We anticipate that patients in the intervention groups will require less postoperative morphine for pain control.
Time Frame	24 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Morphine
Arm/Group Description	36 patients were analyzed for primary outcome. One patient did not receive allocated intervention (failed spinal), One PCA data was lost, and 4 patients remained intubated overnight.	Intrathecal morphine group
Measure Participants	36	33
Median (Inter-Quartile Range) [Miligram]	59	28

2. Secondary Outcome

Title	Pain Score
Description	Patients will score their pain on a visual analog scale of 0-10. The higher the score, the worse the patients reported pain is at that time .
Time Frame	First 48 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Morphine
Arm/Group Description	Intrathecal saline group	Intrathecal Morphine Group
Measure Participants	37	33
Median (Inter-Quartile Range) [score on a scale]	6	1.2

3. Secondary Outcome

Title	Patient Satisfaction
Description	Patients will take a satisfaction survey prior to discharge, this is measured by calculating a score on a scale. This survey consist of questions that asks about the subjects post-operative experience with pain. Higher reported scores represent worse post-operative subject experience. These are ranked from a 0-10 scale, where 0 is the best experience and 10 meaning the worst experience. Questions being asked how satisfied they were with the results of the pain treatment while hospitalized, least pain in prior 24 hours, worst pain in prior 24 ours, percent time in severe pain, how much pain interfered with different activities, how much pain caused anxiety, depression, fright, helplessness, how severe were symptoms of nausea, drowsiness, itching, dizziness, and percentage pain relief in prior 24 hours.
Time Frame	1-3 days after surgery, prior to discharge.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Morphine
Arm/Group Description	Intrathecal saline group	Intrathecal Morphine Group
Measure Participants	28	35
Median (Inter-Quartile Range) [score on a scale]	9	9.5

4. Secondary Outcome

Title	Number of Participants With Nausea
Description	Daily evaluation of nausea post-operatively throughout the subjects hospital stay.
Time Frame	Until discharge, 2-3 days after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo (Nausea)	Morphine
Arm/Group Description	Intrathecal saline group	Intrathecal Morphine group
Measure Participants	37	33
Count of Participants [Participants]	3 7.1%	12 32.4%

5. Secondary Outcome

Title	Number of Participants With Respiratory Depression
Description	Opioid related respiratory depression, post-operatively throughout the subjects hospital stay.
Time Frame	During hospital stay

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Morphine
Arm/Group Description	Intrathecal saline group	Intrathecal Morphine group
Measure Participants	37	33
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Each subject was assessed for adverse events throughout their hospital stay, on average this was 1-2 days per participant.
Arm/Group Title	Placebo		Morphine
Arm/Group Description	Intrathecal Saline Group		5 micrograms/kilogram of intrathecal morphine.
All Cause Mortality
	Placebo		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/37 (0%)
Serious Adverse Events
	Placebo		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/37 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.