Sickle Cell Disease
Conditions
Brief summary
The purpose of this research study is to compare two different ways to give opioid pain medicine to treat sickle cell disease pain that is bad enough to go to the emergency department for treatment. One way uses your weight to decide how much pain medicine to give you while in the emergency department. This is called weight based treatment. The other way uses how much pain medicine you take at home and how much medicine you needed during past emergency department visits to decide how much medicine to give you. This is called patient specific treatment.
Interventions
OTHERPatient-Specific Protocol
Patients assigned to this treatment protocol will be given pain medicine(s) based on the pain medicine(s) they take at home for pain and what was needed during their past hospital and emergency department visits to treat pain. Medicines will include opioids, either morphine or hydromorphone. A member of the outpatient SCD provider team will review the patient's medical record to determine: 1) the patient's maximum home opioid dose, and 2) previous ED analgesic medication(s) and doses that have been effective and safe in the past. The patient's regular hematologist/sickle cell team will write the treatment plans. Medications will be given every 20-30 minutes for up to 6 hours.
OTHERWeight-based Protocol
Patients assigned to this treatment protocol will be given pain medicine(s) based on their weight. Medicines will include opioids, either morphine or hydromorphone. Plans will be written by the patients regular hematologist/sickle cell team.
DRUGMorphine
4 mg for participants weighing \<50 kgs, 6mg for participants weighing 50-69.9 kgs, 8mg for participants weighing 70 - 89.9 kgs and 10mg for participants weighing greater than or equal to 90 kgs. dose is given. Re-dosing is every 20-30 minutes up to 6 hours with one possible dose escalation of 25%.
DRUGHydromorphone
1 mg for participants weighing \<60 kgs, 1.5 mg for participants weighing 60 - 89.9 kgs, and 2 mg for participants weighing greater than or equal to 90 kgs. dose is given. Re-dosing is every 20-30 minutes up to 6 hours with one possible dose escalation of 25%.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All adult (18 years or older); * Sickle Cell Disease patients with the following genotypes: Hgb SS (sickle cell anemia), SC(Sickle hemoglobin-c) , and SB+(sickle Beta-Plus thalassemia) and SB-(sickle Beta zero thalassemia)
Exclusion criteria
* determined to not benefit from opioids and therefore won't receive opioids in any future Emergency Department visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Pain Score | baseline (bed placement), to disposition decision or a maximum treatment duration of 6 hours, whichever came first | Pain is measured by having the patient mark pain on a scale of 0 to 100, with 0 being no pain and 100 being the worst pain ever. Pain scores were initially measured using a 0-100 millimeter visual analog scale with higher (closer to 100 being worse); however during the COVID-19 pandemic, one site removed paper forms from the emergency department as an infection control measure. The protocol was amended to add collection of a 0-100 verbal numerical rating scale and sites were ask to obtain both a vision and verbal score if possible collecting the visual score first. For the analysis, the visual score was used if available for the primary outcome. if not available, the verbal score was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Index ED (Emergency Department) Stay | From bed placement to discharge or 6 hours whichever comes first | Length of index ED stay in hours from bed placement to discharge |
| Length of Care | up to 6 hours | Length of care from bed placement to last drug dose in hours. |
| Total Number of Hospitalizations for Vaso-Occlusive Episode 7 Days Post Enrollment | Up to 7 days post enrollment | Number of hospitalizations for Vaso-Occlusive Episode (VOE) within 7 days following enrollment |
| Number of Participants Experiencing Side Effects | Bed placement to discharge or 6 hours, whichever comes first | Side effects and safety at any time during the emergency department visit |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between August 13, 2019 - May 13 2022 at 6 academic institutions. Institutions selected based on minimum average of two ED (Emergency Department) visits/day by patients with SCD(Sickle Cell Disease) for treatment of VOE (Vaso-occlusive pain events), hematologist willing to randomize patients to the treatment arms, informatics support to post the protocols in electronic health record and infrastructure to support both enrollment of subjects and prospective data collection.
Pre-assignment details
Participants were consented & randomized in ED, clinic or by phone with the onset of COVID-19. Pain protocols were written based on the randomization arm assigned and uploaded to the Electronic Medical Record for use if the participant presented to the emergency department (ED) for pain related to their sickle cell disease. Patients were evaluated for COVID-19 at the ED visit & excluded if COVID positive. During the ED visit, baseline date were collected following bed placement of participant.
Participants by arm
| Arm | Count |
|---|---|
| Patient-Specific Protocol Patients assigned to this arm will be given pain medicine(s) based on pain medicine(s) they take at home and what was needed during their past hospital and emergency department visits to treat pain. Medicines include opioids, either morphine or hydromorphone. An outpatient SCD provider team will review patient's medical record to determine: 1) the patient's maximum home opioid dose, and 2) previous ED analgesic medication(s) and doses that have been effective & safe in the past. The patient's regular hematologist/sickle cell team will write the treatment plans. Medications will be given every 20-30 minutes for up to 6 hours.
Morphine: 4 mg for participants weighing \<50 kgs, 6mg for participants weighing 50-69.9 kgs, 8mg for participants weighing 70 - 89.9 kgs and 10mg for participants weighing greater than or equal to 90 kgs. dose is given. Re-dosing is every 20-30 minutes up to 6 hours with one possible dose escalation of 25%.
Hydromorphone: 1 mg for participants weighing \<60 kgs, 1.5 mg for participants weighing 60 - 89.9 kgs, and 2 mg for participants weighing greater than or equal to 90 kgs. dose is given. Re-dosing is every 20-30 minutes up to 6 hours with one possible dose escalation of 25%. | 54 |
| Weight-based Protocol Patients assigned to this treatment protocol will be given pain medicine(s) based on their weight.
Weight-based Protocol: Patients assigned to this treatment protocol will be given pain medicine(s) based on their weight. Medicines will include opioids, either morphine or hydromorphone. Plans will be written by the patients regular hematologist/sickle cell team.
Morphine: 4 mg for participants weighing \<50 kgs, 6mg for participants weighing 50-69.9 kgs, 8mg for participants weighing 70 - 89.9 kgs and 10mg for participants weighing greater than or equal to 90 kgs. dose is given. Re-dosing is every 20-30 minutes up to 6 hours with one possible dose escalation of 25%.
Hydromorphone: 1 mg for participants weighing \<60 kgs, 1.5 mg for participants weighing 60 - 89.9 kgs, and 2 mg for participants weighing greater than or equal to 90 kgs. dose is given. Re-dosing is every 20-30 minutes up to 6 hours with one possible dose escalation of 25%. | 50 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Confirmed COVID-19 | 1 | 2 |
| Overall Study | Emergency Department visit for non vaso-occlusive episode diagnosis | 18 | 15 |
| Overall Study | Missed emergency department visit | 25 | 30 |
| Overall Study | missing pain score | 1 | 1 |
| Overall Study | No emergency department visit | 65 | 71 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Patient-Specific Protocol | Total | Weight-based Protocol |
|---|---|---|---|
| Acute Chest Syndrome | 39 Participants | 74 Participants | 35 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 104 Participants | 50 Participants |
| Age, Continuous | 31.3 Years STANDARD_DEVIATION 8.63 | 30.3 Years STANDARD_DEVIATION 8.48 | 29.3 Years STANDARD_DEVIATION 8.28 |
| Avascular necrosis | 22 Participants | 39 Participants | 17 Participants |
| Clinical Genotypes SC SB+ | 12 Participants | 27 Participants | 15 Participants |
| Clinical Genotypes SS, SB | 42 Participants | 77 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 101 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gallbladder disease | 18 Participants | 33 Participants | 15 Participants |
| Heart Failure | 3 Participants | 4 Participants | 1 Participants |
| Kidney dysfunction | 2 Participants | 7 Participants | 5 Participants |
| Leg Ulcers | 3 Participants | 5 Participants | 2 Participants |
| Liver Dysfunction | 3 Participants | 3 Participants | 0 Participants |
| Pulmonary Hypertension | 10 Participants | 16 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 53 Participants | 101 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 54 Participants | 104 Participants | 50 Participants |
| Retinopathy | 2 Participants | 6 Participants | 4 Participants |
| Seizure | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Female | 36 Participants | 64 Participants | 28 Participants |
| Sex: Female, Male Male | 18 Participants | 39 Participants | 21 Participants |
| Stroke | 11 Participants | 19 Participants | 8 Participants |
| Transient ischemic attack | 3 Participants | 4 Participants | 1 Participants |
| Weight | 73.8 kg STANDARD_DEVIATION 16.63 | 74.0 kg STANDARD_DEVIATION 16.49 | 74.2 kg STANDARD_DEVIATION 16.49 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 46 |
| other Total, other adverse events | 50 / 50 | 46 / 46 |
| serious Total, serious adverse events | 0 / 50 | 0 / 46 |
Outcome results
Primary
The Change in Pain Score
Pain is measured by having the patient mark pain on a scale of 0 to 100, with 0 being no pain and 100 being the worst pain ever. Pain scores were initially measured using a 0-100 millimeter visual analog scale with higher (closer to 100 being worse); however during the COVID-19 pandemic, one site removed paper forms from the emergency department as an infection control measure. The protocol was amended to add collection of a 0-100 verbal numerical rating scale and sites were ask to obtain both a vision and verbal score if possible collecting the visual score first. For the analysis, the visual score was used if available for the primary outcome. if not available, the verbal score was used.
Time frame: baseline (bed placement), to disposition decision or a maximum treatment duration of 6 hours, whichever came first
Population: 3 participants were excluded following COVID-19 diagnosis, 5 participants had missing data following baseline so analysis could not be made.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient-Specific Protocol | The Change in Pain Score | -27.0 score on a scale | Standard Deviation 27.54 |
| Weight-based Protocol | The Change in Pain Score | -27.6 score on a scale | Standard Deviation 28.13 |
p-value: 0.909Regression, Linear
Secondary
Length of Care
Length of care from bed placement to last drug dose in hours.
Time frame: up to 6 hours
Population: Data not collected on 10 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient-Specific Protocol | Length of Care | 2.5 hours | Standard Deviation 1.46 |
| Weight-based Protocol | Length of Care | 2.6 hours | Standard Deviation 1.62 |
Secondary
Length of Index ED (Emergency Department) Stay
Length of index ED stay in hours from bed placement to discharge
Time frame: From bed placement to discharge or 6 hours whichever comes first
Population: Patients had to be placed in bed in emergency department. Time was calculated from placement to change in disposition or at the end of 6 hours whichever came first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient-Specific Protocol | Length of Index ED (Emergency Department) Stay | 3.4 hours | Standard Deviation 1.48 |
| Weight-based Protocol | Length of Index ED (Emergency Department) Stay | 4.2 hours | Standard Deviation 1.72 |
Secondary
Number of Participants Experiencing Side Effects
Side effects and safety at any time during the emergency department visit
Time frame: Bed placement to discharge or 6 hours, whichever comes first
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | Moderate to severe sedation (sedation score of >=3 | 4 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | pruritus | 31 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | Nausea | 19 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | SPO2<95% requiring supplemental oxygen via nasal cannula due to opioid therapy | 4 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | respiratory depression not requiring intubation | 0 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | Drowsiness | 15 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | Low blood pressure (SBP,90mmHg and/or DBP<50mmHg | 3 Participants |
| Patient-Specific Protocol | Number of Participants Experiencing Side Effects | vomiting | 7 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | Low blood pressure (SBP,90mmHg and/or DBP<50mmHg | 1 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | Moderate to severe sedation (sedation score of >=3 | 5 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | Drowsiness | 9 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | Nausea | 19 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | vomiting | 6 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | pruritus | 36 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | respiratory depression not requiring intubation | 1 Participants |
| Weight-based Protocol | Number of Participants Experiencing Side Effects | SPO2<95% requiring supplemental oxygen via nasal cannula due to opioid therapy | 7 Participants |
Secondary
Total Number of Hospitalizations for Vaso-Occlusive Episode 7 Days Post Enrollment
Number of hospitalizations for Vaso-Occlusive Episode (VOE) within 7 days following enrollment
Time frame: Up to 7 days post enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Specific Protocol | Total Number of Hospitalizations for Vaso-Occlusive Episode 7 Days Post Enrollment | 11 hospitalizations |
| Weight-based Protocol | Total Number of Hospitalizations for Vaso-Occlusive Episode 7 Days Post Enrollment | 14 hospitalizations |