Safety Study of Intravenous Hydromorphone Using Incremental 1mg Doses up to 2mg for Adult ED Patients
Information source: Montefiore Medical Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pain
Intervention: Hydromorphone (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: Montefiore Medical Center
Official(s) and/or principal investigator(s):
Andrew Chang, M.D., Principal Investigator, Affiliation: Motefiore Medical Center
We wish to examine the safety and speed of onset of giving a dose of 1mg hydromorphone
followed by an additional 1mg. Eligible patients will be given 1 mg IV hydromorphone. At 15
minutes, these patients will be asked the question, "Do you need more pain medication?"
Those that answer "yes" will receive an additional 1mg IV hydromorphone. Those that answer
"no" will not receive additional pain medications at that time period (15 minutes). Thus, we
wish to give up to 2 mg IV hydromorphone titrated to patients' pain, which we believe will
result in less incidence of oxygen desaturation.
If our study shows that this regimen is safe, its efficacy can be assessed in future trials.
Positive results of those trials may lead to the use of this regimen to improve pain
management in the emergency department.
Official title: Safety and Speed of Onsent of Intravenous Hydromorphone Using Incremental 1mg Doses up to 2mg in the Treatment of Adult ED Patients With Moderate to Severe Pain
Study design: Treatment, Open Label, Single Group Assignment, Safety Study
Primary outcome: Incidence of a serious adverse event by 120 minutes post infusion, which is defined as the use of naloxone as a reversal agent
Minimum age: 21 Years.
Maximum age: 64 Years.
1. Age greater than 21 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.
2. Age less than 65 years of age: Patients age 65 and over will be excluded in this
study as the effects on opioids on the elderly may be different than in the
3. Pain with onset within 7 days: Pain within seven days is the definition of acute pain
that has been used in ED literature.
4. ED attending physician's judgment that patient's pain warrants use of morphine: The
factors that influence the decision to use parenteral 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
hydromorphone 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, unless there is a restriction to
patients with a specific diagnosis, 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.
5. The use of patients with a variety of diagnoses, and therefore heterogeneous painful
stimuli, risks masking a treatment effect because of large inter-individual
variability. There are several design and analytic factors (detailed below) that
attenuate this risk: 1) a sufficiently large number of patients will be randomly
assigned to each group so that the variety of painful stimuli will be equally
distributed between treatment groups; 2) change in pain intensity and pain relief will
be analyzed rather than absolute pain intensity or pain relief therefore reducing
6. 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
1. Prior use of methadone: the effect of methadone use on the perception of acute pain is
unknown and suspected to be altered. We feel that the needs of patients on methadone
may exceed the dosage ceiling of 2mg that will be used for this study. Similar to
sickle cell patients and chronic cancer patients, patients on methadone usually
require significantly higher doses of opioids to control their pain. Thus, we feel
that it would be unethical to restrict the dose that this subset of patients can
2. Use of other opioids or tramadol within past seven days: to avoid introducing bias
related to opioid tolerance that may alter the response to the study medication
thereby masking the medication's effect.
3. Prior adverse reaction to hydromorphone.
4. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months result
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 as judged by the treating
physician may alter perception, report, and treatment of pain.
6. SBP <90 mm Hg: Hydromorphone can produce peripheral vasodilation that may result in
orthostatic hypotension or syncope.
7. Oxygen saturation <95% on room air: For this study, oxygen saturation must be 95% or
above on room air in order to be enrolled.
8. Use of MAO inhibitors in past 30 days: MAOs have been reported to intensify the
effects of at least one opioid drug causing anxiety, confusion and significant
respiratory depression or coma.
9. C02 measurement greater than 46: In accordance with a similar study (04-12-360),
three 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 3 subsets are as follows:
1. All patients who have a history of COPD
2. All patients who report a history of asthma together with greater than a 20
pack-year smoking history
3. All patients reporting less than a 20 pack-year smoking history who are having an
10. Pregnancy: this will be determined by asking the female of reproductive age about her
pregnancy status and/or through the results of urine or serum pregnancy test.
Locations and Contacts
Montefiore Medical Center, Bronx, New York 10467, United States
Starting date: June 2007
Last updated: May 21, 2008