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Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT02222246
Recruitment Status : Completed
First Posted : August 21, 2014
Results First Posted : August 4, 2017
Last Update Posted : August 4, 2017
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Cincinnati
Mount Sinai Hospital, New York
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Condition Sickle Cell Disease
Interventions Drug: Hydromorphone (Standardized, weight-based dosing)
Drug: Morphine Sulfate (Standardized, weight-based dosing)
Drug: Hydromorphone (Patient Specific dosing)
Drug: Morphine Sulfate (Patient Specific dosing)
Enrollment 106
Recruitment Details  
Pre-assignment Details 106 subject were enrolled and consented to participation during all future Emergency Department (ED) visits for vaso-occlusive crises (VOC), should they occur, over the study period. 53 subjects were randomized to each arm.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description

A standardized analgesic protocol (based on recent National Heart, Lung, and Blood Institute (NHBLI) recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a Sickle Cell Disease (SCD) specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Period Title: Overall Study
Started 53 53
Completed 26 26
Not Completed 27 27
Reason Not Completed
No Emergency Department Visits             27             26
Physician Decision             0             1
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone Total
Hide Arm/Group Description

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Total of all reporting groups
Overall Number of Baseline Participants 26 26 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 26 participants 26 participants 52 participants
27.0
(23.0 to 33.0)
28.5
(23.0 to 32.0)
27.0
(23.0 to 32.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 26 participants 52 participants
Female
11
  42.3%
11
  42.3%
22
  42.3%
Male
15
  57.7%
15
  57.7%
30
  57.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 26 participants 52 participants
Hispanic or Latino
2
   7.7%
5
  19.2%
7
  13.5%
Not Hispanic or Latino
21
  80.8%
21
  80.8%
42
  80.8%
Unknown or Not Reported
3
  11.5%
0
   0.0%
3
   5.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race/Ethnicity Number Analyzed 26 participants 26 participants 52 participants
African American/Black
23
  88.5%
23
  88.5%
46
  88.5%
Caucasian
3
  11.5%
3
  11.5%
6
  11.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 26 participants 26 participants 52 participants
26
 100.0%
26
 100.0%
52
 100.0%
1.Primary Outcome
Title Difference in Pain Score as Measured by a Visual Analogue Scale (VAS)
Hide Description Each ED study visit was the unit of analysis for the statistical methods addressing the primary outcome. The primary outcome was change in pain score from arrival to discharge. Pain severity was assessed at arrival and discharge from ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating “no pain” and 100 indicating “pain as bad as it could be” or “worst imaginable pain”.Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED. Thus, the difference in pain scores were calculated as the arrival minus discharge VAS scores, with higher positive pain difference or change scores indicating greater pain reduction.
Time Frame Arrival in ED to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Mean (Standard Deviation)
Unit of Measure: Units on a 100 mm VAS
26.4  (10.6) 43.0  (18.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Change in pain scores from arrival to discharge
Statistical Test of Hypothesis P-Value 0.0311
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis for pain change was conducted using Hierarchical Linear Mixed Effects Model (HLM), adjusting for nested patient and site effects (N=126)
2.Secondary Outcome
Title Change in Pain Visual Analogue Scale (VAS) Scores Over Time
Hide Description

Pain severity was assessed at arrival and every 30 minutes until discharge from the ED using a 100 mm visual analogue scale (VAS). The VAS range is 0 to 100 with 0 indicating “no pain” and 100 indicating “pain as bad as it could be” or “worst imaginable pain”. Discharge was defined by which one of the following occurred first: (a) decision to admit to hospital; (b) patient physically leaves the ED to home; or (c) after six hours of observation in the ED.

A hierarchical random coefficients regression model for repeated measurements (type of mixed hierarchical mixed-effect model) was conducted on the pain scores collected at six time points (arrival, post-placement 30-min, 60-min, 90-min,120-min, discharge) to evaluate the trajectory of change in pain. Discharge occurred at 120 minutes or later during each visit, with the exception of one discharge at 54 minutes.

Time Frame Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The entire observation period was not evaluated because the patient-specific protocol has a shorter time to discharge, and, there was data missing at random after 120 minutes. To avoid a biased result, the mixed model was conducted on the data collected every 30 minutes during initial 120 minutes (2 hours) and at discharge.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Mean (Standard Deviation)
Unit of Measure: Units on a 100 mm VAS
Emergency Department Arrival 82.2  (13.0) 82.2  (17.0)
Post-placement 30 minutes 80.6  (13.1) 79.6  (17.1)
Post-placement 60 minutes 79.0  (13.4) 77.2  (17.2)
Post-placement 90 minutes 77.4  (13.7) 74.7  (17.3)
Post-placement 120 minutes 75.9  (14.0) 72.2  (17.6)
Emergency Department Discharge 55.7  (21.9) 40.9  (25.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments The trajectory of change in pain score was evaluated every 30 minutes over 120 hours (2 hours) rather than 6 hours because of expected missing data after 120 minutes due to discharge from the ED.
Type of Statistical Test Non-Inferiority
Comments Trajectory of pain across time (arrival to discharge)
Statistical Test of Hypothesis P-Value 0.0049
Comments p-value for the protocol by time interaction
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Emergency Department Arrival
Statistical Test of Hypothesis P-Value 0.9393
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Post-placement 30 minutes
Statistical Test of Hypothesis P-Value 0.7259
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Post-placement 60 minutes
Statistical Test of Hypothesis P-Value 0.5300
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Post-placement 90 minutes
Statistical Test of Hypothesis P-Value 0.3678
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Post-placement 120 minutes
Statistical Test of Hypothesis P-Value 0.2457
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Emergency Department Discharge
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Incidence of Nausea During Emergency Department Visits
Hide Description Nausea at any point from placement until discharge, based on nausea data collected every 30 minutes during that time period. Thus, a nausea variable was derived in which 0=no and 1=yes that nausea was reported by the patient at least once during the placement to discharge time interval.
Time Frame From placement in Emergency Department (ED) treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods.
Arm/Group Title Patient Specific Dose of Morphine Sulfate or Hydromorphone Standard Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Nausea - No
26
  40.6%
46
  74.2%
Nausea - Yes
38
  59.4%
16
  25.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patient Specific Dose of Morphine Sulfate or Hydromorphone, Standard Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Incidence of nausea during Emergency Department Visit - YES
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Incidence of Vomiting During Emergency Department Visits
Hide Description Vomiting at any point from placement until discharge, based on vomiting data collected every 30 minutes during that time period. Thus, a vomiting variable was derived in which 0=no and 1=yes that vomiting was reported by the patient at least once during the placement to discharge time interval.
Time Frame From placement in ED treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Vomiting - No
54
  84.4%
54
  87.1%
Vomiting - Yes
10
  15.6%
8
  12.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Incidence of vomiting (YES) during Emergency Department visit
Statistical Test of Hypothesis P-Value 0.6625
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
5.Secondary Outcome
Title Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit
Hide Description Decrease in systolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A systolic variable was derived in which 0=no and 1=yes that a >= 20% decrease of baseline systolic blood pressure was reported by the patient at least once during the placement to discharge time interval.
Time Frame From placement in ED treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Decrease in systolic BP - No
55
  85.9%
56
  90.3%
Decrease in systolic BP - Y
9
  14.1%
6
   9.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Decrease in systolic BP (>= 20% of baseline)
Statistical Test of Hypothesis P-Value 0.4473
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
6.Secondary Outcome
Title Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit
Hide Description Decrease in diastolic blood pressure at any point from placement until discharge, based on blood pressure data collected every 30 minutes during that time period. A diastolic variable was derived in which 0=no and 1=yes that a > 20% decrease of baseline diastolic blood pressure was reported by the patient at least once during the placement to discharge time interval.
Time Frame From placement in ED treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Decrease in diastolic BP - No
40
  62.5%
42
  67.7%
Decrease in diastolic BP - Y
24
  37.5%
20
  32.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Decrease in diastolic blood pressure (>= 20% baseline)
Statistical Test of Hypothesis P-Value 0.5372
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
7.Secondary Outcome
Title Incidence of Oxygen Desaturation (< 95%) (YES) During Emergency Department Visit
Hide Description Saturation of peripheral capillary oxygen < 95% (SPO2 < 95%) at any point from placement until discharge, based on SPO2 data collected every 30 minutes during that time period. Thus, a SPO2 variable was derived in which 0=no and 1=yes that SPO2 < 95% was reported by the patient at least once during the placement to discharge time interval.
Time Frame From placement in ED treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
SpO2 < 95% - No
27
  42.2%
32
  51.6%
SpO2 < 95% - Yes
37
  57.8%
30
  48.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Incidence of oxygen desaturation (<95%) YES during Emergency Department visit
Statistical Test of Hypothesis P-Value 0.2891
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
8.Secondary Outcome
Title Incidence of Respiratory Distress (YES) During Emergency Department Visit
Hide Description Respiratory distress at any point from placement until discharge, based on data collected every 30 minutes during that time period. Thus, a respiratory distress variable was derived in which 0=no and 1=yes that respiratory distress was reported by the patient at least once during the placement to discharge time interval.
Time Frame From placement in ED treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Respiratory Distress - No
64
 100.0%
62
 100.0%
Respiratory Distress - Yes
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Incidence of Sedation During Emergency Department Visit
Hide Description Severe-to moderate sedation at any point from placement until discharge, based on sedation data collected every 30 minutes during that time period. Thus, a sedation variable was derived in which 0=no and 1=yes that moderate-severe sedation was reported by the patient at least once during the placement to discharge time interval. Sedations scoring was as follows: None was defined as "awake and alert", Mild sedation was defined as "responds to voice", Moderate sedation was defined as "responds to touch, with or without voice" and Severe sedation was defined as "somnolent, difficult to arouse".
Time Frame From placement in ED treatment room to discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
none to mild sedation
51
  79.7%
53
  85.5%
moderate to severe sedation
13
  20.3%
9
  14.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Incidence of sedation during Emergency Department visit.
Statistical Test of Hypothesis P-Value 0.3915
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
10.Secondary Outcome
Title Incidence of the Need for Supplemental Oxygen During Emergency Department Visit
Hide Description Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.
Time Frame Following the initiation of opioid therapy until discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
O2 needed - No
49
  76.6%
55
  88.7%
O2 needed - Yes
15
  23.4%
7
  11.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Dose of Morphine Sulfate or Hydromorphone, Patient Specific Dose of Morphine Sulfate or Hydromorphone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Incidence of the need for supplemental oxygen during Emergency Department visit
Statistical Test of Hypothesis P-Value 0.0726
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
11.Secondary Outcome
Title Incidence of the Administration of Naloxone During Emergency Department Visit
Hide Description Naloxone administered during the Emergency Department stay; this was determined at discharge.
Time Frame Following the initiation of opioid therapy until discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Naloxone administered - No
64
 100.0%
62
 100.0%
Naloxone administered - Yes
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Incidence of the Need for Assistive Ventilation
Hide Description Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.
Time Frame Following the initiation of opioid therapy until discharge from the ED, up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.
Arm/Group Title Standard Dose of Morphine Sulfate or Hydromorphone Patient Specific Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description:

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Overall Number of Participants Analyzed 26 26
Overall Number of Units Analyzed
Type of Units Analyzed: Emergency Department Visits
64 62
Count of Units
Unit of Measure: Emergency Department Visits
Assistive Ventilation - No
64
 100.0%
62
 100.0%
Assistive Ventilation - Yes
0
   0.0%
0
   0.0%
Time Frame Adverse Events were collected on study subjects from time of admission to the Emergency Department until discharge from the Emergency Department, decision to admit to hospital, or up to 6 hours, whichever came first.
Adverse Event Reporting Description Adverse Events were defined as intubation and/or admission to the Intensive Care Unit.
 
Arm/Group Title Patient Specific Dose of Morphine Sulfate or Hydromorphone Standard Dose of Morphine Sulfate or Hydromorphone
Hide Arm/Group Description

A patient-specific analgesic protocol for use in the ED to manage VOC crises. Following randomization, a patient's healthcare team will develop a specific analgesic protocol for use during future ED visits for VOC occurring during the study period (up to 6 visits). Treatment protocols will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous). Dosage and frequency will be based on a patient's prior treatment history.

Hydromorphone (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

Morphine Sulfate (Patient Specific dosing): Patient specific analgesic management, with specific opioid dosage and frequency based on a protocol developed by a patient's healthcare team.

A standardized analgesic protocol (based on recent NHLBI recommendations) for use in the ED to manage VOC crises. Treatment protocol will include either morphine sulfate or hydromorphone (delivered intravenous or sub-cutaneous), with dosage based on weight. Repeat doses of opioids may be administered every 20-30 minutes as needed, although dosage will be maintained or provided at no more than 25% above the initial dose.

Hydromorphone (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

Morphine Sulfate (Standardized, weight-based dosing): Standardized analgesic management using a SCD specific standard protocol based on NHBLI guidelines (initial opioid dose weight-based).

All-Cause Mortality
Patient Specific Dose of Morphine Sulfate or Hydromorphone Standard Dose of Morphine Sulfate or Hydromorphone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Patient Specific Dose of Morphine Sulfate or Hydromorphone Standard Dose of Morphine Sulfate or Hydromorphone
Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/26 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Patient Specific Dose of Morphine Sulfate or Hydromorphone Standard Dose of Morphine Sulfate or Hydromorphone
Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/26 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Paula Tanabe
Organization: Duke University
Phone: 919-613-6038
EMail: paula.tanabe@duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02222246     History of Changes
Other Study ID Numbers: Pro00054047
R34 RHL121224A ( Other Grant/Funding Number: NHLBI )
First Submitted: August 19, 2014
First Posted: August 21, 2014
Results First Submitted: May 12, 2017
Results First Posted: August 4, 2017
Last Update Posted: August 4, 2017