Trial Outcomes & Findings for Titration of Intravenous Hydromorphone (NCT NCT01892709)

Last Updated: 2023-05-31

Results Overview

This is a descriptive hypothesis-generating trial, which is why it is not being compared in a randomized fashion to a comparison group. We are examining extended titration by expanding our "1+1" protocol to a "1+1+1+1" protocol and the various patterns of opioid request. For example, some may state "no" every time they are asked "Do you want more pain medication?" Some will state "yes" each time, and others will answer "yes" and "no" at different time periods. We will report these various patterns (i.e. X participants answered "no" everytime they were asked, Y answered "yes" everytime they were asked, Z answered "no" twice, etc). Time points 2, 3, and 4 are dependent on patient response to "Do you want more pain medication?" Time 1 is 30 min post-baseline. For those who answer "no", Time 2 is 30 minutes later (at 1 hour), and for yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

215 participants

Primary outcome timeframe

4 hours

Results posted on

2023-05-31

Participant Flow

Participant milestones

Participant milestones
Measure	Hydromorphone All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone
Overall Study STARTED	215
Overall Study COMPLETED	215
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Titration of Intravenous Hydromorphone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hydromorphone n=207 Participants All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone
Age, Continuous	41 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants
Sex: Female, Male Male	85 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	143 Participants n=5 Participants
Race/Ethnicity, Customized Black	44 Participants n=5 Participants
Race/Ethnicity, Customized White/Other	20 Participants n=5 Participants
Region of Enrollment United States	207 Participants n=5 Participants
Weight	177 lbs STANDARD_DEVIATION 34 • n=5 Participants
Location of pain Abdomen/pelvis	153 Participants n=5 Participants
Location of pain Flank	22 Participants n=5 Participants
Location of pain Back	15 Participants n=5 Participants
Location of pain Extremities	8 Participants n=5 Participants
Location of pain Other	9 Participants n=5 Participants
Initial NRS pain intensity NRS = 5-7	21 Participants n=5 Participants
Initial NRS pain intensity NRS = 8	27 Participants n=5 Participants
Initial NRS pain intensity NRS = 9	41 Participants n=5 Participants
Initial NRS pain intensity NRS = 10	118 Participants n=5 Participants
Nauseated or vomited before receiving first dose of opioid	134 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 hours

Outcome measures

Outcome measures
Measure	Hydromorphone n=207 Participants All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone	2 mg Hydromorphone Received 2 mg of IV hydromorphone, in 2 1-mg doses.	3 mg Hydromorphone Received 3 mg of IV hydromorphone, in 3 1-mg doses	4 mg Hydromorphone Received 4 mg of IV hydromorphone, in 4 1-mg doses
Number of Participants Requesting Pain Medication in Different Patterns Over Time No requests for additional pain medication	94 Participants	—	—	—
Number of Participants Requesting Pain Medication in Different Patterns Over Time Requested additional pain medication, Time 1 only	20 Participants	—	—	—
Number of Participants Requesting Pain Medication in Different Patterns Over Time Requested additional pain medication, Time 2 only	22 Participants	—	—	—
Number of Participants Requesting Pain Medication in Different Patterns Over Time Requested additional pain medication, Time 3 only	19 Participants	—	—	—
Number of Participants Requesting Pain Medication in Different Patterns Over Time Requested additional pain medication, Time 4 only	18 Participants	—	—	—
Number of Participants Requesting Pain Medication in Different Patterns Over Time Requested add'l pain medication at >1 time point	2 Participants	—	—	—

SECONDARY outcome

Timeframe: 120 min

Population: Nausea and vomiting were only assessed as adverse events among patients who did not have nausea and vomiting before the study began

Outcome measures

Outcome measures
Measure	Hydromorphone n=114 Participants All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone	2 mg Hydromorphone n=78 Participants Received 2 mg of IV hydromorphone, in 2 1-mg doses.	3 mg Hydromorphone n=9 Participants Received 3 mg of IV hydromorphone, in 3 1-mg doses	4 mg Hydromorphone n=6 Participants Received 4 mg of IV hydromorphone, in 4 1-mg doses
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Vomiting	4 Participants	5 Participants	0 Participants	0 Participants
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Oxygen saturation <95%	3 Participants	5 Participants	1 Participants	0 Participants
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Respiratory Rate <10 breaths/min	1 Participants	0 Participants	1 Participants	0 Participants
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Pulse rate <50 beats/min	1 Participants	1 Participants	0 Participants	0 Participants
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Systolic blood pressure <90 mmHg	1 Participants	0 Participants	0 Participants	0 Participants
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Pruritus	8 Participants	8 Participants	2 Participants	2 Participants
Adverse Events and Side Effects by Total Amount of Hydromorphone Received Nausea	6 Participants	14 Participants	2 Participants	3 Participants

POST_HOC outcome

Timeframe: 4 hours

Time points 2, 3, and 4 are dependent on patient response to "Do you want more pain medication?" Time 1 is 30 min post-baseline. For those who answer "no" at Time 1, Time 2 is 30 minutes later (at 1 hour), and for those who answer yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours

Outcome measures

Outcome measures
Measure	Hydromorphone n=207 Participants All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone	2 mg Hydromorphone Received 2 mg of IV hydromorphone, in 2 1-mg doses.	3 mg Hydromorphone Received 3 mg of IV hydromorphone, in 3 1-mg doses	4 mg Hydromorphone Received 4 mg of IV hydromorphone, in 4 1-mg doses
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 4 · No	168 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 1 · Yes	42 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 1 · No	165 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 2 · Yes	41 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 2 · No	166 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 3 · Yes	31 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 3 · No	176 Participants	—	—	—
Number of Patients Responding to the Question, "Do You Want More Pain Medication?" at Each Time Point Time 4 · Yes	39 Participants	—	—	—

POST_HOC outcome

Timeframe: 4 hours

Pain intensity is measured on the numerical rating scale (NRS) with scores from 0 ("no pain") to 10 ("worst pain imaginable"). Time points 2, 3, and 4 are dependent on patient response to "Do you want more pain medication?" Time 1 is 30 min post-baseline. For those who answer "no" at Time 1, Time 2 is 30 minutes later (at 1 hour), and for those who answer yes, Time 2 is 30 minutes after additional pain medication is given. This pattern follows for Time 3 and 4, with a total study time of 4 hours

Outcome measures

Outcome measures
Measure	Hydromorphone n=207 Participants All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone	2 mg Hydromorphone Received 2 mg of IV hydromorphone, in 2 1-mg doses.	3 mg Hydromorphone Received 3 mg of IV hydromorphone, in 3 1-mg doses	4 mg Hydromorphone Received 4 mg of IV hydromorphone, in 4 1-mg doses
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 1, Yes	7.4 units on a scale Interval 3.0 to 10.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 1, No	3.8 units on a scale Interval 0.0 to 10.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 2, Yes	7.2 units on a scale Interval 4.0 to 10.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 2, No	2.9 units on a scale Interval 0.0 to 7.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 3, Yes	7.1 units on a scale Interval 3.0 to 10.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 3, No	3.1 units on a scale Interval 0.0 to 10.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 4, Yes	6.8 units on a scale Interval 0.0 to 10.0	—	—	—
Mean Pain Intensity Score in Numerical Rating Scale (NRS) Units at Each Time Point, Based on Response to the Question, "Do You Want More Pain Medication?" Time 4, No	2.4 units on a scale Interval 0.0 to 8.0	—	—	—

Adverse Events

Hydromorphone

Serious events: 0 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Hydromorphone n=207 participants at risk All eligible patients will receive 1 mg IV hydromorphone. Thereafter, they will be repeatedly asked the question, "Do you want more pain medicine?" This question will be asked 30 minutes after they answered "no" or 30 minutes after the completion of the next dose of 1 mg IV hydromorphone, which occurs when the patients answers "yes". Patients will receive a maximum of 4 mg IV hydromorphone over a 4 hour period. Hydromorphone
Respiratory, thoracic and mediastinal disorders Oxygen saturation <95%	4.3% 9/207 • 120 minutes
Respiratory, thoracic and mediastinal disorders Respiratory rate < 10 breaths/min	0.97% 2/207 • 120 minutes
Vascular disorders Pulse rate < 50 beats/min	0.97% 2/207 • 120 minutes
Vascular disorders Systolic blood pressure < 90 mmHg	0.48% 1/207 • 120 minutes
Skin and subcutaneous tissue disorders Pruritus	9.7% 20/207 • 120 minutes
Gastrointestinal disorders Nausea	41.7% 25/60 • 120 minutes
Gastrointestinal disorders Vomiting	15.0% 9/60 • 120 minutes

Additional Information

Andrew Chang, MD, MS

Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore Medical Center

Phone: 718-920-7476

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place