Back to results

Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

Primary Purpose

Lumbar Disc Disease, Spinal Fusion, Degenerative Disc Disease

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Propranolol Hcl 40mg Tab

Placebo oral tablet

About this trial

This is an interventional treatment trial for Lumbar Disc Disease focused on measuring lumbar fusion, propranolol, beta-blockers, post-surgical pain, opioid-sparing

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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

Sites / Locations

Duke University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Propranolol treatment

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Acute postoperative opioid use at 24 hours

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

Acute postoperative opioid use at 48 hours

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

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 opioid use at 4 weeks

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 opioid use at 12 weeks

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).

Acute postoperative pain scores at 24 hours

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.

Acute postoperative pain scores at 48 hours

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.

Sub-acute postoperative pain scores at 1 week

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

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.

Sub-acute postoperative pain scores at 12 weeks

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.

Full Information

NCT ID

NCT04421209

First Posted

June 4, 2020

Last Updated

March 12, 2021

Sponsor

Duke University

Collaborators

Foundation for Anesthesia Education and Research

1. Study Identification

Unique Protocol Identification Number

NCT04421209

Brief Title

Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

Official Title

Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Withdrawn

Why Stopped

No funding source

Study Start Date

December 2020 (Anticipated)

Primary Completion Date

June 30, 2021 (Anticipated)

Study Completion Date

September 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Duke University

Collaborators

Foundation for Anesthesia Education and Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lumbar Disc Disease, Spinal Fusion, Degenerative Disc Disease

Keywords

lumbar fusion, propranolol, beta-blockers, post-surgical pain, opioid-sparing

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Propranolol treatment

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Propranolol Hcl 40mg Tab

Other Intervention Name(s)

CAS No 525-66-6, DIN: 00496499, Inderal

Intervention Description

40mg PO BID for the three days prior to surgery, 40mg PO BID the day of surgery and on post-op days 1 and 2.

Intervention Type

Drug

Intervention Name(s)

Placebo oral tablet

Other Intervention Name(s)

Tablet containing microcrystalline dextrose, Sugar pill, dextrose pill

Intervention Description

Placebo tablets administered with the same schedule of Propranolol tablets

Primary Outcome Measure Information:

Title

Acute postoperative opioid use at 24 hours

Description

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).

Time Frame

24 hours postoperatively

Secondary Outcome Measure Information:

Title

Acute postoperative opioid use at 48 hours

Description

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).

Time Frame

48 hours postoperatively

Title

Sub-acute postoperative opioid use at 1 week

Description

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).

Time Frame

1 week postoperatively

Title

Sub-acute postoperative opioid use at 4 weeks

Description

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).

Time Frame

4 weeks postoperatively

Title

Sub-acute postoperative opioid use at 12 weeks

Description

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).

Time Frame

12 weeks postoperatively

Title

Acute postoperative pain scores at 24 hours

Description

Time Frame

24 hours post-op

Title

Acute postoperative pain scores at 48 hours

Description

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.

Time Frame

48 hours post-op

Title

Sub-acute postoperative pain scores at 1 week

Description

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.

Time Frame

1 week postoperatively

Title

Sub-acute postoperative pain scores at 4 weeks

Description

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.

Time Frame

4 weekspostoperatively

Title

Sub-acute postoperative pain scores at 12 weeks

Description

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.

Time Frame

12 weeks postoperatively

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Buchheit, MD

Organizational Affiliation

Department of Anesthesiology, Duke University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Stephan Frangakis, MD/PhD

Organizational Affiliation

Department of Anesthesiology, Duke University

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

William Maixner, DDS/PhD

Organizational Affiliation

Department of Anesthesiology, Duke University

Official's Role

Study Director

Facility Information:

Facility Name

Duke University Hospital

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29209205

Citation

Afify EA, Andijani NM. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems. Front Pharmacol. 2017 Nov 10;8:794. doi: 10.3389/fphar.2017.00794. eCollection 2017.

Results Reference

background

PubMed Identifier

26950706

Citation

Ciszek BP, O'Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral beta-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122-35. doi: 10.1097/ALN.0000000000001070.

Results Reference

background

PubMed Identifier

24237004

Citation

Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014 Jan;30(1):149-60. doi: 10.1185/03007995.2013.860019. Epub 2013 Nov 15.

Results Reference

background

PubMed Identifier

24727346

Citation

Hartung JE, Ciszek BP, Nackley AG. beta2- and beta3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain. 2014 Jul;155(7):1346-1355. doi: 10.1016/j.pain.2014.04.011. Epub 2014 Apr 13.

Results Reference

background

PubMed Identifier

16698416

Citation

Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

Results Reference

background

PubMed Identifier

19418100

Citation

Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6.

Results Reference

background

PubMed Identifier

19411061

Citation

Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain. 2009 May;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006.

Results Reference

background

PubMed Identifier

17084978

Citation

Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain. 2007 Apr;128(3):199-208. doi: 10.1016/j.pain.2006.09.022. Epub 2006 Nov 7.

Results Reference

background

PubMed Identifier

30021647

Citation

Page MG, Kudrina I, Zomahoun HTV, Ziegler D, Beaulieu P, Charbonneau C, Cogan J, Daoust R, Martel MO, Neron A, Richebe P, Clarke H. Relative frequency and risk factors for long-term opioid therapy following surgery and trauma among adults: a systematic review protocol. Syst Rev. 2018 Jul 18;7(1):97. doi: 10.1186/s13643-018-0760-3.

Results Reference

background

PubMed Identifier

6213289

Citation

Stanley TH, de Lange S, Boscoe MJ, de Bruijn N. The influence of chronic preoperative propranolol therapy on cardiovascular dynamics and narcotic requirements during operation in patients with coronary artery disease. Can Anaesth Soc J. 1982 Jul;29(4):319-24. doi: 10.1007/BF03007519.

Results Reference

background

PubMed Identifier

20216107

Citation

Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab.

Results Reference

background

Citation

Teimoori, B., Khoshfetrat, M., Beyrami, F., Sakhavar, N., Dehbashi, Z., Narouie, B., & Davarian, A. Propranolol decreases the post-operative pain and analgesic administration following abdominal hysterectomy. Life Sciences Journal 9: 1216-1220, 2012.

Results Reference

background

PubMed Identifier

29226500

Citation

Zanelatto FB, Dias EV, Teixeira JM, Sartori CR, Parada CA, Tambeli CH. Anti-inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action. Eur J Pain. 2018 Mar;22(3):572-582. doi: 10.1002/ejp.1143. Epub 2017 Dec 11.

Results Reference

background

Learn more about this trial

Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

We'll reach out to this number within 24 hrs