Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

Phase 2

Withdrawn

• Conditions: Degenerative Disc Disease; Lumbar Disc Disease; Spinal Fusion
• Interventions: Drug: Propranolol Hcl 40mg Tab; Drug: Placebo oral tablet

• Registration Number: NCT04421209
• Lead Sponsor: Duke University

Brief Summary

The purpose of this study is to determine if treatment with low-dose oral propranolol in the days before and after surgery decrease postoperative pain and improve pain scores.

Detailed Description

This study is a randomized, double-blind, placebo controlled clinical trial.The main purpose of this study is to determine if postsurgical opioid use and pain scores are decreased with oral Propranolol treatment. The treatment period will last for six days and the observation period will last for three months. Effectiveness of treatment will be assessed by means of post-operative opioid consumption as primary outcome measure.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-06-04
• Study First Submitted QC: 2020-06-04
• Study First Posted: 2020-06-09
• Study Start: 2020-12
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-12
• Last Update Posted: 2021-03-16
• Primary Completion: 2021-06-30
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Male or female patients age >18 undergoing elective spinal fusion surgery, with plans to remain inpatient for ≥ 48hrs and receive IV or oral opioids;
• Females of child bearing potential must test negative on a pregnancy test at Visit 1 and utilize acceptable means of birth control for the duration of the study;
• Patients must be judged by the study team to be likely to be reliable and to agree to keep all appointments for clinic visits, tests, and procedures required by the protocol;
• Patients must have the ability to fully participate in the informed consent process.

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Exclusion Criteria

• Disease-related: History of exercise- or exertion-induced asthma or current treatments for asthma; Unstable medical or neurological illness; Heart block greater than first degree (EKG); History of coronary artery disease, or history of congestive heart failure; Baseline heart rate or blood pressure that in the opinion of the investigator would constitute too great a risk when considered in the context of the patient's medical comorbidities and health history; Significant suicidal or homicidal ideation, or current DSM-IV diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition; History of diabetes
• Exposure-related: History of β-blocker use within six months of enrollment in the trial; Total baseline preoperative opioid consumption greater than 50 oral milligram morphine equivalents (MME) per day; Current use or use within the past two weeks of methadone, levorphanol, buprenorphine, butorphanol, pentazocine, tramadol, nalbuphine, naloxone, or naltrexone.
• Patient characteristics: Female patients who are pregnant or breast-feeding; Known allergy to study medication; Alcohol/substance abuse within past six months; Ongoing or anticipated disability compensation or litigation issues, in the best judgement of the investigator; Presence of any factors/conditions, medical or other, that in the judgment of the investigator may interfere with performance of study outcome measures, such as treatment-refractory history; Non-ambulatory or require the use of crutches or a walker; No access to a telephone

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Propranolol treatment	Propranolol Hcl 40mg Tab	Subjects randomized to the propranolol treatment arm will be administered propranolol 40mg BID for three days prior to surgery, 40mg BID the day of surgery and on post-operative days 1 and 2. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered. Patients will be evaluated for opioid usend pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op. Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers, and if this correlates to decreased opioid use and pain scores post-operatively. All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management.
Placebo	Placebo oral tablet	Subjects randomized to the placebo treatment arm will be administered placebo tablets with the same schedule as propranolol in the experimental arm. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered. Patients will be evaluated for opioid use and pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op. Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers compared to placebo, and if this correlates to decreased opioid use and pain scores post-operatively. All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management.

Primary Outcome Measures

Name	Time	Method
Acute postoperative opioid use at 24 hours	24 hours postoperatively	Total opioid use from 0 to 24 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).

Secondary Outcome Measures

Name	Time	Method
Acute postoperative opioid use at 48 hours	48 hours postoperatively	Total opioid use from 24 to 48 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).
Sub-acute postoperative opioid use at 1 week	1 week postoperatively	Patient reported current opioid use for the prior 24 hours will be quantified at 1 week post-op. Opioid use will be converted to standard oral morphine equivalents (OME).
Sub-acute postoperative pain scores at 1 week	1 week postoperatively	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 1 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
Sub-acute postoperative pain scores at 4 weeks	4 weekspostoperatively	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 4 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
Acute postoperative pain scores at 24 hours	24 hours post-op	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 24 post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
Sub-acute postoperative opioid use at 12 weeks	12 weeks postoperatively	Patient reported current opioid use for the prior 24 hours will be quantified at 12 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).
Sub-acute postoperative opioid use at 4 weeks	4 weeks postoperatively	Patient reported current opioid use for the prior 24 hours will be quantified at 4 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).
Sub-acute postoperative pain scores at 12 weeks	12 weeks postoperatively	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 12 weeks post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
Acute postoperative pain scores at 48 hours	48 hours post-op	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 48 hours post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.

Trial Locations

Locations (1)

Duke University Hospital; 🇺🇸 Durham, North Carolina, United States