Intravenous Buprenorphine Versus Morphine for Severe Pain in the Emergency Department

This study evaluates intravenous (IV) buprenorphine versus IV morphine for the management of severe, acute pain among emergency department (ED) patients. ED patients with severe pain will be randomized in equal proportion to receive IV buprenorphine or IV morphine.

Study Overview

• Status: Unknown
• Conditions: Pain
• Intervention / Treatment: Drug: Buprenorphine; Drug: Morphine Sulfate

Detailed Description

Buprenorphine is classified as a partial mu opioid agonist and a weak kappa antagonist. In lower doses, buprenorphine has an analgesic potency 25 to 40 times more potent than similar milligram dosages of morphine. Consistent with its partial agonist activity, an apparent ceiling effect for opioid-induced ventilatory impairment has been demonstrated. These properties would suggest that buprenorphine is an effective analgesic with a favorable safety profile.

Objective: The objective of this study is to determine if there is a clinically significant difference in reduction of pain scores, measured by the Numeric Rating Scale (NRS), between intravenous (IV) buprenorphine and IV morphine for severe pain in patients presenting to the Alameda Health System--Highland Hospital ED. The investigators are evaluating if IV buprenorphine is non-inferior to IV morphing. The investigators hypothesize that buprenorphine will provide equivalent analgesic effects as morphine at 60 minutes, with a lower proportion of medication adverse effects.

Study Design: This is a double-blinded, randomized controlled non-inferiority trial comparing the analgesic efficacy of intravenous buprenorphine versus intravenous morphine for ED patients presenting with severe, acute pain.

Participants: ED patients aged ≥18 years old who present with severe (pain NRS ≥7), acute pain warranting (according the treating provider's judgment) and able to receive IV opioid analgesia. The investigators will exclude pregnant patients, patients deemed too critically ill by the provider, patients with allergy to buprenorphine or morphine, patients in custody, patients on methadone, patients who have taken/received short acting opioid medications in the last 12 hours, and patients who have taken/received long acting opioid medication in the past 24 hours.

Intervention: In arm A, patients will receive IV Buprenorphine 0.3mg diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minute. In arm B, patients will receive IV morphine 0.1mg/kg (max 10mg) over 3-5 minutes. In both arms, at 20 minutes the patient will be asked "would you like more pain medication?" If he/she answers "yes", then he/she will receive a second dose of the same amount of medication they previously received based on the randomized arm they were placed into. At the end of the study time, 60 minutes, the patient's ongoing pain management will be left to the attending physician caring for the patient in the ED.

Data Collection: For both arms, the patients' NRS pain scores and adverse effects will be queried at times 0, 10min, 20 min, 30min, 40min, 50 min, and 60 min. Demographic and comorbidity data points will be abstracted during or after the study's conclusion.

• Study Type: Interventional
• Enrollment (Anticipated): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94602
      • Recruiting
      • Alameda Health System, Highland Hospital
      • Contact: David K Duong, MD MS; Phone Number: 617-412-5111; Email: dduong@alamedahealthsystem.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ED patients with acute pain NRS ≥7 warranting IV opioid analgesia (according to ED provider)

Exclusion Criteria:

• Patient refusal

• pregnancy

  • level 1 trauma patients
  • patients deemed critically ill by provider
  • patients in custody
  • patients on methadone
  • Patients who have received or taken any short acting opioid medication in the past 12 hours.
  • Patients who have received or taken any long acting opioid medication in the past 24 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buprenorphine; Patients will receive IV buprenorphine 0.3mg diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minutes. At 20 minutes, the patient will be asked "would you like more pain medication?" If he/she answers "yes", then he/she will receive a second dose of IV buprenorphine 0.3mg.	Drug: Buprenorphine; buprenorphine 0.3mg IV
Active Comparator: Morphine; Patients will receive IV morphine 0.1mg/kg (max dose 8mg) diluted to a volume of 10mL with NS in a plastic syringe administered over 3-5 minutes. At 20 minutes, the patient will be asked "would you like more pain medication?" If he/she answers "yes", then he/she will receive a second dose of IV morphine 0.1mg/kg (max dose 8mg).	Drug: Morphine Sulfate; morphine 0.1 mg/kg IV (max 8mg per dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score difference at 60 minutes	The difference in pain scores (measured by NRS) between the two arms at 60 minutes.	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score difference at 50 minutes	The difference in pain scores (measured by NRS) between the two arms.	50 minutes
Pain score difference at 40 minutes	The difference in pain scores (measured by NRS) between the two arms.	40 minutes
Pain score difference at 30 minutes	The difference in pain scores (measured by NRS) between the two arms.	30 minutes
Pain score difference at 20 minutes	The difference in pain scores (measured by NRS) between the two arms.	20 minutes
Pain score difference at 10 minutes	The difference in pain scores (measured by NRS) between the two arms.	10 minutes
Adverse events	Hypertension (SBP > 180) from documented vital signs,hypotension (SBP <90) from documented vital signs, hypoxia (oxygen saturation < 90%), respiratory depression (RR<8 or need for mechanical intervention), nausea, vomiting, symptoms of opiate withdrawal (diarrhea, abdominal pain, diaphoresis)	10, 20, 30, 40, 50, and 60 minutes
Pain reduction	Pain reduction at each time point. Measured by NRS (time 0) minus NRS (time x)	10, 20, 30, 40, 50, and 60 minutes
Successful analgesia	Proportion of patients with NRS < 3 at 60 minutes	60 minutes
Repeat dosing	Proportion of patients requiring reducing of analgesia at 20 minutes	20 minutes
Summed Pain Intensity difference	Measurement combining relief magnitude and duration in a single score	60 minutes

Collaborators and Investigators

• Sponsor: Alameda Health System

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2017
• Primary Completion (Anticipated): February 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Morphine
• Other Study ID Numbers: IRB17-04172B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes