IV Acetaminophen as Adjuvant Analgesic to Hydromorphone - Emergency Department Patients

Randomized Clinical Trial of IV Acetaminophen as an Adjuvant Analgesic to IV Hydromorphone for Treatment of Acute Severe Pain in Non-Elderly Emergency Department Patients

The goal of this randomized clinical trial is to compare the analgesic efficacy and side effect profile of IV acetaminophen as an analgesic adjunctive medication to IV hydromorphone for the treatment of acute pain experienced by patients in the Emergency Department (ED).

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: IV acetaminophen; Drug: hydromorphone; Drug: IV placebo

Detailed Description

Multimodal treatment of pain is a commonly used strategy to control pain by combining analgesics with different and complementary mechanisms of action. Oral acetaminophen combined with opioids is a mainstay of treatment of mild to moderate pain, while the use of IV opioids is the standard for treatment of severe pain in the Emergency Department. An IV formulation of acetaminophen is widely used in Europe and has recently been approved in the US. It has been studied for treatment of acute post-operative pain and renal colic.

This randomized trial was designed to assess the effectiveness of the combination of IV acetaminophen and IV hydromorphone as a strategy to provide more effective treatment of acute severe pain in the Emergency Department with the possibility of reducing opioid consumption. All patients received 1 mg of IV hydromorphone. They were then randomized to receive either 1 g of IV acetaminophen or 100 mL of normal saline placebo. Measures of pain, vital signs, and presence of side effects were obtained immediately before IV hydromorphone was administered. Following receipt of the acetaminophen or placebo these same variables were measured at 15 minute intervals for the next 120 minutes. Additional analgesics were administered if patients requested them. Subsequent care of the patients was at the discretion of the treating attending physician.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 64 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pain with onset within 7 days of the ED visit
• ED attending physician's judgment that the patient's pain warrants IV opioids.
• ED attending physician's judgment that the patient has capacity to provide informed consent.
• ED attending physician's judgement that patient is not a chronic user of opioids or acetaminophen
• Patients must be able to understand English or Spanish.

Exclusion Criteria:

• Use of opioids or tramadol within past 24 hours.
• Use of acetaminophen or non-steroidal anti-inflammatory medication within the previous 8 hours.
• Prior adverse reaction to opioids or acetaminophen.
• Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months; examples of chronic pain syndromes include sickle cell anemia, osteoarthritis, fibromyalgia, and peripheral neuropathies.
• Medical condition that might affect metabolism or opioid analgesics or acetaminophen such as hepatitis, renal insufficiency or failure, hypo- or hyper-thyroidism, Addison's or Cushing's disease
• Pregnant or breastfeeding
• Alcohol intoxication: the presence of alcohol intoxication as judged by the treating physician or nurse
• Not at risk of suicide assessed by triage nurse
• Systolic blood pressure <100 mmHg
• Heart Rate < 60/min
• Oxygen saturation < 95% on room air:
• Use of monoamine oxidase (MAO) inhibitors in past 30 days
• Use of transdermal pain patches
• Taking any medication that might interact with one of the study medications, such as a selective serotonin reuptake inhibitor (SSRI) or tricyclic anti-depressants, antipsychotics, anti-malarial medications (quinidine or halofantrine), amiodarone or dronedarone, diphenhydramine, celecoxib, ranitidine, cimetidine, ritonavir, terbinafine or St. John's Wort.
• Patients who have been previously enrolled in this same study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV hydromorphone and IV acetaminophen; 1000 mg IV acetaminophen administered over 5-10 minutes 1 mg hydromorphone administered over 5-10 minutes	Drug: IV acetaminophen; acetaminophen given intravenously; Other Names: Ofirmev; Drug: hydromorphone; hydromorphone given intravenously; Other Names: Dilaudid
Placebo Comparator: IV hydromorphone and placebo; 100 ml IV normal saline administered over 5-10 minutes 1 mg hydromorphone administered over 5-10 minutes	Drug: hydromorphone; hydromorphone given intravenously; Other Names: Dilaudid; Drug: IV placebo; given intravenously; Other Names: normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Numerical Rating Scale of Pain (NRS) Before Treatment to 60 Minutes After Treatment	The between group difference in change in NRS pain scores from before administration of study medications to 60 minutes post administration of study medications. The NRS is a previously validated and reproducible measure of pain intensity ranging from 0 = no pain, to 10 = worst possible pain. Higher values indicate more pain relief from before treatment to 60 minutes after treatment	Before treatment to 60 minutes after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Received Additional Pain Medication Within 60 Minutes of Administration of Study Medication	Difference in percentage of patients who received additional pain medication within 60 minutes of administration of study medication in the two arms of the study	Baseline to 60 minutes post-baseline
Percentage of Patients Who Received Additional Pain Medication Between 61 and 120 Minutes After Administration of Study Medications	Difference in percentage of patients who received additional pain medication between 61 and 120 minutes after administration of study medication by study group	61 to 120 minutes post-baseline
Percentage of Patients Who Want Additional Analgesics	Number of patients who answer "yes" to question: "Do you want more pain medication" divided by number of patients	Immediately after administration of study medication to 120 minutes after administration of study medication

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Investigators: Principal Investigator: Polly Bijur, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2018
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: May 10, 2018
• First Submitted That Met QC Criteria: May 30, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: pain; randomized controlled trial; Emergency Department; acetaminophen; hydromorphone; opioid analgesics
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease Attributes; Emergencies; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Acetaminophen; Hydromorphone
• Other Study ID Numbers: 2018-8886

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