Protocolized vs Nonprotocolized Treatment of Adult ED Patients With Acute Severe Pain

A Randomized Controlled Trial Comparing Protocolized Versus Non-protocolized Treatment of Adult ED Patients With Acute Severe Pain

Patients treated with protocolized pain management (1 mg of IV hydromorphone followed by an additional 1 mg IV hydromorphone if the patient wants more) will have better pain relief and no more adverse events than patients receiving non-protocolized pain management.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Hydromorphone; Drug: Nonprotocolized

• Study Type: Interventional
• Enrollment (Actual): 224
• 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: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 21 to 64 years: Patients under the age of 21 are automatically triaged to the Children's Hospital at Montefiore Emergency Department, and hence cannot be enrolled in this study. Age 64 was selected as an upper range for inclusion because substantial evidence supports age as being an important determinant of morphine requirement over longer periods of time.
2. Pain with onset within 7 days: Pain within seven days is the definition of acute pain that has been used in ED literature.
3. Emergency Department (ED) attending physician's judgment that patient's pain warrants use of intravenous opioids: The factors that influence the decision to use intravenous opioids are complex and extensive. An approach that is commonly taken to address the issue of patient selection in drug trials is to use a specific condition (e.g., renal colic) or treatment (e.g., post-hysterectomy) that would generally be thought to be appropriately treated with an opioid analgesic, thereby eliminating individual judgment about eligibility for the study. However in order to assess the role of intravenous (IV) opioids with the widest generalizability in the ED setting, we decided to enroll patients with a variety of diagnoses, all with a complaint of acute pain. Opioids are not an appropriate treatment for all patients who present with a complaint of pain (e.g., gastroenteritis, migraine). Therefore either a comprehensive list of diagnoses and situations in which opioids are indicated must be specified, or clinical judgment needs to be used. We have opted for the latter alternative.
4. Normal mental status: In order to provide measures of pain experienced the patient needs to have a normal mental status. Orientation to person, place and time will be used as an indicator of sufficiently normal mental status to participate in the study.

Exclusion Criteria:

1. Prior use of methadone: the effect of methadone use on the perception of acute pain is unknown and suspected to be altered.
2. Use of other opioids, tramadol, or heroin in the past seven days: to avoid introducing bias related to opioid tolerance that may alter the response to intravenous opioids thereby masking the effects of the medications administered.
3. Prior adverse reaction to morphine, hydromorphone, or other opioids: An exception will be if the patient has received opioid medications in the past without adverse event (i.e. a patient may state he is allergic to morphine but has received hydromorphone in the past without any adverse effects)
4. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months resulting in alteration in pain perception which is thought to be due to down-regulation of pain receptors. Examples of chronic pain syndromes include sickle cell anemia, osteoarthritis, fibromyalgia, migraine, and peripheral neuropathies.
5. Alcohol intoxication: the presence of alcohol intoxication may alter the perception, report, and treatment of pain. Alcohol intoxication will be determined to exist as judged by the treating physician.
6. Systolic Blood Pressure < 90 mm Hg: Opioids produce peripheral vasodilation that may result in orthostatic hypotension or syncope.
7. Use of monoamine oxidase (MAO) inhibitors in past 30 days: MAO inhibitors have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant depression of respiration or coma.
8. Weight less than 100 pounds: we are concerned that hydromorphone in doses up to 2 mg may not be safe in patients weighing less than 100 lbs.
9. Baseline room air oxygen saturation less than 95%: since IV opioids may cause respiratory depression and result in hypoxemia, we are excluding this subgroup of patients.

10. C02 measurement greater than 46: In accordance with a similar study (04-12-360), four subsets of patients will have their CO2 measured using a handheld capnometer prior to enrollment in the study. If the CO2 measurement is greater than 46, then the patient will be excluded from the study. The 4 subsets are as follows:

    1. All patients who have a history of chronic obstructive pulmonary disease (COPD)
    2. All patients who have a history of sleep apnea
    3. All patients who report a history of asthma together with greater than a 20 pack-year smoking history
    4. All patients reporting less than a 20 pack-year smoking history who are having an asthma exacerbation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protocolized; 1mg IV hydromorphone followed by an additional 1mg at 15 minutes if the patient answer "yes" to the question, "Do you want more pain medication?"	Drug: Hydromorphone; Hydromorphone 1mg IV, followed by an optional dose of 1mg IV hydromorphone 15 minutes; Other Names: Dilaudid
Active Comparator: Nonprotocolized; An IV opioid the type and dose of which will be determined by the treating clincian	Drug: Nonprotocolized; An IV opioid the type and dose of which will be determined by the treating clinician; Other Names: Usual Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Change in Pain Intensity From Initial Administration of Analgesics (Baseline) to 60 Minutes Post-baseline.	Pain intensity is rated on the numerical rating scale (NRS), measured in integer units from 0 ("no pain") to 10 ("worst pain imaginable"). The change in pain intensity subtracts the NRS score given by the patient 60 minutes after treatment was administered from the baseline NRS score (before treatment in the Emergency Department).	60 minutes

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Andrew Chang, M.D., Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: February 21, 2008
• First Submitted That Met QC Criteria: February 29, 2008
• First Posted (Estimate): March 3, 2008

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Acute Pain, Emergency Department, ED, Hydromorphone, Dilaudid Protocolized Nonprotocolized Usual Care
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: MMC 0710359