Acute Pain
Conditions
Keywords
pain, opioid analgesics, Emergency Department, randomized controlled trial, acetaminophen, hydromorphone
Brief summary
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).
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.
Interventions
DRUGIV acetaminophen
acetaminophen given intravenously
DRUGIV placebo
given intravenously
DRUGhydromorphone
hydromorphone given intravenously
Sponsors
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The pharmacist working in an area inaccessible to ED staff will ensure blinding by creating identical vials containing either 1000 mg acetaminophen in 100 ml normal saline or 100 ml normal saline placebo and numbering them sequentially for use in this study.
Intervention model description
Randomized Clinical Trial
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Numerical Rating Scale of Pain (NRS) Before Treatment to 60 Minutes After Treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Received Additional Pain Medication Within 60 Minutes of Administration of Study Medication | Baseline to 60 minutes post-baseline | 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 |
| Percentage of Patients Who Received Additional Pain Medication Between 61 and 120 Minutes After Administration of Study Medications | 61 to 120 minutes post-baseline | Difference in percentage of patients who received additional pain medication between 61 and 120 minutes after administration of study medication by study group |
| Percentage of Patients Who Want Additional Analgesics | Immediately after administration of study medication to 120 minutes after administration of study medication | Number of patients who answer yes to question: Do you want more pain medication divided by number of patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV Hydromorphone and IV Acetaminophen 1000 mg IV acetaminophen administered over 5-10 minutes
IV acetaminophen: acetaminophen given intravenously
1 mg hydromorphone: hydromorphone given intravenously | 80 |
| IV Hydromorphone and Placebo 100 ml IV normal saline administered over 5-10 minutes
IV placebo: given intravenously
1 mg hydromorphone: hydromorphone given intravenously | 79 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Missing primary outcome | 1 | 2 |
Baseline characteristics
| Characteristic | IV Hydromorphone and IV Acetaminophen | IV Hydromorphone and Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 12 | 43.1 years STANDARD_DEVIATION 13.5 | 43.2 years STANDARD_DEVIATION 12.8 |
| Location of Pain Abdomen/flank | 70 Participants | 67 Participants | 137 Participants |
| Location of Pain Other | 10 Participants | 12 Participants | 22 Participants |
| Nauseated or vomited in Emergency Department before treatment No - not nauseated, did not vomit | 23 Participants | 27 Participants | 50 Participants |
| Nauseated or vomited in Emergency Department before treatment Yes - nauseated or vomited | 57 Participants | 52 Participants | 109 Participants |
| Pain Intensity on Numerical Rating Scale 10 | 50 Participants | 43 Participants | 93 Participants |
| Pain Intensity on Numerical Rating Scale 6-7 | 7 Participants | 8 Participants | 15 Participants |
| Pain Intensity on Numerical Rating Scale 8 | 12 Participants | 19 Participants | 31 Participants |
| Pain Intensity on Numerical Rating Scale 9 | 11 Participants | 9 Participants | 20 Participants |
| Race/Ethnicity, Customized Race/ethnicity African-American | 22 Participants | 17 Participants | 39 Participants |
| Race/Ethnicity, Customized Race/ethnicity Hispanic/Latino | 54 Participants | 53 Participants | 107 Participants |
| Race/Ethnicity, Customized Race/ethnicity Other | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Race/ethnicity White | 2 Participants | 5 Participants | 7 Participants |
| Region of Enrollment United States | 80 participants | 79 participants | 159 participants |
| Sex: Female, Male Female | 52 Participants | 48 Participants | 100 Participants |
| Sex: Female, Male Male | 28 Participants | 31 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 79 |
| other Total, other adverse events | 21 / 80 | 22 / 79 |
| serious Total, serious adverse events | 0 / 80 | 0 / 79 |
Outcome results
Primary
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
Time frame: Before treatment to 60 minutes after treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IV Hydromorphone and IV Acetaminophen | Change in Numerical Rating Scale of Pain (NRS) Before Treatment to 60 Minutes After Treatment | 6.2 units on a scale |
| IV Hydromorphone and Placebo | Change in Numerical Rating Scale of Pain (NRS) Before Treatment to 60 Minutes After Treatment | 5.4 units on a scale |
p-value: 0.08t-test, 2 sided
Secondary
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
Time frame: 61 to 120 minutes post-baseline
Population: All patients in study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Hydromorphone and IV Acetaminophen | Percentage of Patients Who Received Additional Pain Medication Between 61 and 120 Minutes After Administration of Study Medications | 2 Participants |
| IV Hydromorphone and Placebo | Percentage of Patients Who Received Additional Pain Medication Between 61 and 120 Minutes After Administration of Study Medications | 4 Participants |
p-value: 0.414Chi-squared
Secondary
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
Time frame: Baseline to 60 minutes post-baseline
Population: All patients in the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Hydromorphone and IV Acetaminophen | Percentage of Patients Who Received Additional Pain Medication Within 60 Minutes of Administration of Study Medication | 2 Participants |
| IV Hydromorphone and Placebo | Percentage of Patients Who Received Additional Pain Medication Within 60 Minutes of Administration of Study Medication | 2 Participants |
p-value: 0.989Chi-squared
Secondary
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
Time frame: Immediately after administration of study medication to 120 minutes after administration of study medication
Population: Patients who were still in Emergency Department 120 minutes after medication was administered
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Hydromorphone and IV Acetaminophen | Percentage of Patients Who Want Additional Analgesics | 21 Participants |
| IV Hydromorphone and Placebo | Percentage of Patients Who Want Additional Analgesics | 29 Participants |
p-value: 0.153Chi-squared