Trial Outcomes & Findings for Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease (NCT NCT02222246)

NCT ID: NCT02222246

Last Updated: 2017-08-04

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 106 participants
• Primary outcome timeframe: Arrival in ED to discharge from the ED, up to 6 hours
• Results posted on: 2017-08-04

Participant Flow

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.

Participant milestones

Measure	Standard Dose of Morphine Sulfate or Hydromorphone 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone 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 Study STARTED	53	53
Overall Study COMPLETED	26	26
Overall Study NOT COMPLETED	27	27

Reasons for withdrawal

Measure	Standard Dose of Morphine Sulfate or Hydromorphone 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone 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 Study No Emergency Department Visits	27	26
Overall Study Physician Decision	0	1

Baseline Characteristics

Comparing Acute Pain Management Protocols for Patients With Sickle Cell Disease

Baseline characteristics by cohort

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=26 Participants 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=26 Participants 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 n=52 Participants Total of all reporting groups
Age, Continuous	27.0 years n=5 Participants	28.5 years n=7 Participants	27.0 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · African American/Black	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Caucasian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants

PRIMARY outcome

Timeframe: Arrival in ED to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Difference in Pain Score as Measured by a Visual Analogue Scale (VAS)	26.4 Units on a 100 mm VAS Standard Deviation 10.6	43.0 Units on a 100 mm VAS Standard Deviation 18.6

SECONDARY outcome

Timeframe: Every 30 minutes from arrival in ED to discharge from the ED, up to 6 hours

Population: 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.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Change in Pain Visual Analogue Scale (VAS) Scores Over Time Post-placement 90 minutes	77.4 Units on a 100 mm VAS Standard Deviation 13.7	74.7 Units on a 100 mm VAS Standard Deviation 17.3
Change in Pain Visual Analogue Scale (VAS) Scores Over Time Emergency Department Arrival	82.2 Units on a 100 mm VAS Standard Deviation 13.0	82.2 Units on a 100 mm VAS Standard Deviation 17.0
Change in Pain Visual Analogue Scale (VAS) Scores Over Time Post-placement 30 minutes	80.6 Units on a 100 mm VAS Standard Deviation 13.1	79.6 Units on a 100 mm VAS Standard Deviation 17.1
Change in Pain Visual Analogue Scale (VAS) Scores Over Time Post-placement 60 minutes	79.0 Units on a 100 mm VAS Standard Deviation 13.4	77.2 Units on a 100 mm VAS Standard Deviation 17.2
Change in Pain Visual Analogue Scale (VAS) Scores Over Time Post-placement 120 minutes	75.9 Units on a 100 mm VAS Standard Deviation 14.0	72.2 Units on a 100 mm VAS Standard Deviation 17.6
Change in Pain Visual Analogue Scale (VAS) Scores Over Time Emergency Department Discharge	55.7 Units on a 100 mm VAS Standard Deviation 21.9	40.9 Units on a 100 mm VAS Standard Deviation 25.4

SECONDARY outcome

Timeframe: From placement in Emergency Department (ED) treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of Nausea During Emergency Department Visits Nausea - No	26 Emergency Department Visits	46 Emergency Department Visits
Incidence of Nausea During Emergency Department Visits Nausea - Yes	38 Emergency Department Visits	16 Emergency Department Visits

SECONDARY outcome

Timeframe: From placement in ED treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of Vomiting During Emergency Department Visits Vomiting - Yes	10 Emergency Department Visits	8 Emergency Department Visits
Incidence of Vomiting During Emergency Department Visits Vomiting - No	54 Emergency Department Visits	54 Emergency Department Visits

SECONDARY outcome

Timeframe: From placement in ED treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit Decrease in systolic BP - No	55 Emergency Department Visits	56 Emergency Department Visits
Incidence of a Decrease in Systolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit Decrease in systolic BP - Y	9 Emergency Department Visits	6 Emergency Department Visits

SECONDARY outcome

Timeframe: From placement in ED treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit Decrease in diastolic BP - Y	24 Emergency Department Visits	20 Emergency Department Visits
Incidence of a Decrease in Diastolic Blood Pressure Greater Than or Equal to 20% of Baseline During Emergency Department Visit Decrease in diastolic BP - No	40 Emergency Department Visits	42 Emergency Department Visits

SECONDARY outcome

Timeframe: From placement in ED treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of Oxygen Desaturation (< 95%) (YES) During Emergency Department Visit SpO2 < 95% - No	27 Emergency Department Visits	32 Emergency Department Visits
Incidence of Oxygen Desaturation (< 95%) (YES) During Emergency Department Visit SpO2 < 95% - Yes	37 Emergency Department Visits	30 Emergency Department Visits

SECONDARY outcome

Timeframe: From placement in ED treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

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.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of Respiratory Distress (YES) During Emergency Department Visit Respiratory Distress - No	64 Emergency Department Visits	62 Emergency Department Visits
Incidence of Respiratory Distress (YES) During Emergency Department Visit Respiratory Distress - Yes	0 Emergency Department Visits	0 Emergency Department Visits

SECONDARY outcome

Timeframe: From placement in ED treatment room to discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

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".

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of Sedation During Emergency Department Visit moderate to severe sedation	13 Emergency Department Visits	9 Emergency Department Visits
Incidence of Sedation During Emergency Department Visit none to mild sedation	51 Emergency Department Visits	53 Emergency Department Visits

SECONDARY outcome

Timeframe: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

Need for supplemental oxygen during the Emergency Department stay; this was determined at discharge.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of the Need for Supplemental Oxygen During Emergency Department Visit O2 needed - No	49 Emergency Department Visits	55 Emergency Department Visits
Incidence of the Need for Supplemental Oxygen During Emergency Department Visit O2 needed - Yes	15 Emergency Department Visits	7 Emergency Department Visits

SECONDARY outcome

Timeframe: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

Naloxone administered during the Emergency Department stay; this was determined at discharge.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of the Administration of Naloxone During Emergency Department Visit Naloxone administered - No	64 Emergency Department Visits	62 Emergency Department Visits
Incidence of the Administration of Naloxone During Emergency Department Visit Naloxone administered - Yes	0 Emergency Department Visits	0 Emergency Department Visits

SECONDARY outcome

Timeframe: Following the initiation of opioid therapy until discharge from the ED, up to 6 hours

Population: Each Emergency Department study visit was the unit of analysis for the statistical methods addressing the primary outcome.

Intubation or other assistive ventilation techniques - including bag, valve, or mask was performed during the ED stay; this was determined at discharge.

Outcome measures

Measure	Standard Dose of Morphine Sulfate or Hydromorphone n=64 Emergency Department Visits 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).	Patient Specific Dose of Morphine Sulfate or Hydromorphone n=62 Emergency Department Visits 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.
Incidence of the Need for Assistive Ventilation Assistive Ventilation - No	64 Emergency Department Visits	62 Emergency Department Visits
Incidence of the Need for Assistive Ventilation Assistive Ventilation - Yes	0 Emergency Department Visits	0 Emergency Department Visits

Adverse Events

Patient Specific Dose of Morphine Sulfate or Hydromorphone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Standard Dose of Morphine Sulfate or Hydromorphone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Paula Tanabe

Duke University

Phone: 919-613-6038

Email: paula.tanabe@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place