Acute Pain
Conditions
Brief summary
Intravenous opioids are the mainstay of acute, severe pain treatment in Emergency Departments (ED) across the country. Acetaminophen, given orally, has also been used for treatment of mild to moderate pain. The more potent intravenous (IV) form of acetaminophen has been widely used in Europe for more than 20 years as post-surgical analgesia and received full FDA approval in the USA in 2010. As part of a continuing set of studies whose goal is to optimize treatment of pain among elderly ED patients, this randomized study will compare efficacy and safety of IV acetaminophen to IV hydromorphone.
Interventions
DRUGAcetaminophen 1000mg IV
1000mg of IV acetaminophen in 100ml of normal saline, administered as an intravenous drip over 10 minutes + 2ml of normal saline, administered as a slow intravenous push
DRUGHydromorphone 0.5 mg IV
100ml of normal saline, administered as an intravenous drip over 10 minutes, + 0.5mg of IV hydromorphone in 2ml of normal saline, administered as a slow intravenous push
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age equal to 65 or greater 2. Pain onset within 7 days with severe pain 3. Has capacity to provide informed consent 4. Understanding English or Spanish
Exclusion criteria
1. Use of tramadol or opioids within 7 days 2. Use of acetaminophen or non-steroidal anti-inflammatory medications within 8 hours 3. Chronic pain syndrome: daily pain for \> 3 months. Sickle cell anemia, osteoarthritis, fibromyalgia, and peripheral neuropathies 4. Conditions which may affect acetaminophen or opioid metabolism such as cirrhosis (Child Pugh A or worse), kidney impairment (CKD 3 or worse), active hepatic disease or severe dehydration 5. Alcohol intoxication 6. Systolic blood pressure: \< 100 mmHg 7. Heart rate: \< 60 beats per minute 8. Oxygen saturation: \< 95% on room air 9. Use of monoamine oxidase (MAO) inhibitors in the past 30 days 10. Use of transdermal pain patch or oral opioid \> 10 days in the prior month 11. Prior enrollment in the same study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement in NRS Pain Score | 60 minutes following administration of medication | Pain improvement was assessed using an NRS (numeric rating scale) to assess pain on a range of 0-10. Participants were asked to verbalize intensity of pain on the scale with zero meaning no pain and 10 meaning the worst pain imaginable. Pain was assessed at baseline and 60 minutes later to determine if clinically important improvement in pain was achieved. Clinically important improvement in pain was defined as an improvement of \>=1.3 points on the 0-10 scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for Rescue Medication | 120 minutes following administration of medication | Number of participants who required additional analgesic medication for the treatment of pain at any time during their ED course. |
| Improvement in NPS Pain Score by >=50% | 60 minutes after administration of medication | The number of patients who minimally achieved a 50% improvement in NPS pain score from 0 to 60 minutes. |
Countries
United States
Participant flow
Recruitment details
Enrollment began in August 2018, paused between March and June 2020, and concluded in October 2021. A total of 2,363 patients were screened for participation of which 162 were enrolled from two urban emergency departments in Bronx, NY.
Participants by arm
| Arm | Count |
|---|---|
| Acetaminophen 1000mg IV Acetaminophen 1000mg IV: 1000mg of IV acetaminophen in 100ml of normal saline, administered as an intravenous drip over 10 minutes + 2ml of normal saline, administered as a slow intravenous push. | 81 |
| Hydromorphone 0.5mg IV Hydromorphone 0.5 mg IV: 100ml of normal saline, administered as an intravenous drip over 10 minutes, + 0.5mg of IV hydromorphone in solution with 2mL of normal saline, administered as a slow intravenous push. | 81 |
| Total | 162 |
Baseline characteristics
| Characteristic | Acetaminophen 1000mg IV | Hydromorphone 0.5mg IV | Total |
|---|---|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 8 | 74 years STANDARD_DEVIATION 6 | 75 years STANDARD_DEVIATION 7 |
| Age, Customized 60-69 years old | 23 Participants | 22 Participants | 45 Participants |
| Age, Customized 70-79 years old | 40 Participants | 45 Participants | 85 Participants |
| Age, Customized 80-89 years old | 12 Participants | 14 Participants | 26 Participants |
| Age, Customized >=90 years old | 6 Participants | 0 Participants | 6 Participants |
| Duration of Pain | 2 Minutes | 2 Minutes | 2 Minutes |
| Location of Pain Abdomen/Flank/Pelvis | 52 Participants | 55 Participants | 107 Participants |
| Location of Pain Back/Neck | 6 Participants | 7 Participants | 13 Participants |
| Location of Pain Chest | 1 Participants | 6 Participants | 7 Participants |
| Location of Pain Extremity | 21 Participants | 11 Participants | 32 Participants |
| Location of Pain Head | 0 Participants | 2 Participants | 2 Participants |
| Location of Pain Widespread | 1 Participants | 0 Participants | 1 Participants |
| NRS Pain Score (0-10) | 10 score on a scale | 10 score on a scale | 10 score on a scale |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 81 participants | 81 participants | 162 participants |
| Sex: Female, Male Female | 56 Participants | 51 Participants | 107 Participants |
| Sex: Female, Male Male | 25 Participants | 30 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 81 |
| other Total, other adverse events | 6 / 81 | 10 / 81 |
| serious Total, serious adverse events | 0 / 81 | 0 / 81 |
Outcome results
Primary
Clinical Improvement in NRS Pain Score
Pain improvement was assessed using an NRS (numeric rating scale) to assess pain on a range of 0-10. Participants were asked to verbalize intensity of pain on the scale with zero meaning no pain and 10 meaning the worst pain imaginable. Pain was assessed at baseline and 60 minutes later to determine if clinically important improvement in pain was achieved. Clinically important improvement in pain was defined as an improvement of \>=1.3 points on the 0-10 scale.
Time frame: 60 minutes following administration of medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen 1000mg IV | Clinical Improvement in NRS Pain Score | 62 Participants |
| Hydromorphone 0.5mg IV | Clinical Improvement in NRS Pain Score | 63 Participants |
Secondary
Improvement in NPS Pain Score by >=50%
The number of patients who minimally achieved a 50% improvement in NPS pain score from 0 to 60 minutes.
Time frame: 60 minutes after administration of medication
Population: Study participants did not receive any additional medication before the assessment of the primary outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen 1000mg IV | Improvement in NPS Pain Score by >=50% | 30 Participants |
| Hydromorphone 0.5mg IV | Improvement in NPS Pain Score by >=50% | 43 Participants |
Secondary
Need for Rescue Medication
Number of participants who required additional analgesic medication for the treatment of pain at any time during their ED course.
Time frame: 120 minutes following administration of medication
Population: Study participants did not receive any additional medication before the assessment of the primary outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen 1000mg IV | Need for Rescue Medication | 37 Participants |
| Hydromorphone 0.5mg IV | Need for Rescue Medication | 31 Participants |