Sickle Cell Disease
Conditions
Brief summary
This study will assess the safety of changing pain medications (opioids) adult sickle cell patients take to another type of medication therapy (buprenorphine). Patients will be asked questions about their quality of life. Other tools for assessment will also be administered.
Detailed description
This is a descriptive, pilot study to assess the safety of converting a subset of adult sickle cell patients who are on effective disease modifying therapy (on high dose oral opioids who are unable to wean off opioids) and who continue to have frequent acute visits where parenteral opioids are administered to convert all opioid treatments to buprenorphine. Quality of life will be assessed using the Adult Sickle Cell Quality of life Measurement tool (ASCQ-Me), the Brief Pain Inventory (BPI), two Patient-Reported Outcomes Measurement Information System (PROMIS) surveys (short-form Pain Interference and Physical Function), and frequency of acute pain visits. Buprenorphine is a partial mu-agonist and kappa antagonist and has a high affinity for the mu receptors with an elimination half-life of 28-37 hours for the sublingual administration. The lower risk for misuse, diminished withdrawal symptoms and cravings for opioids as well as the reduced risk of overdose make it an appealing alternative. Recent data on successful conversion for patients with chronic pain show a decrease in pain scores and increase in quality of life measurements after the beginning buprenorphine therapy for more than two months. The first dose will be determined for each patient by a physician to ensure that the dosage of buprenorphine will be appropriate given the patient's current opioid dosage. There is the risk of withdrawal induced vaso-occlusive crisis (VOC). Within 30 days prior to conversion to buprenorphine, a patient will take the ASCQ-Me, BPI, and two PROMIS surveys. Twenty-four hours prior to conversion, the patient will stop all opioid intake. The day of conversion, the patient will take a Clinical Opiate Withdrawal Scale (COWS) survey to determine whether they are in withdrawal. If so, the patient will begin buprenorphine conversion. They will also retake the aforementioned quality of life surveys. The patient will return on days 1, 14, 30, 90, and 180 to be evaluated.
Interventions
DRUGbuprenorphine
Patients in this study will receive dosages to be determined by a physician that are specific to each patient.
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sickle Cell Disease, any genotype * On disease modifying therapy (either chronic transfusions or hydroxyurea) * On chronic daily full agonist opioid therapy with doses ranging from 90 to 400 morphine equivalents * Have greater than 5 acute care visits in the last 6 months or have daily pain of 7 or higher on the Visual Analog Scale despite chronic opioid therapy. * Able to provide consent * Has medical insurance
Exclusion criteria
* Acute vaso-occlusive crisis on day of or day prior to buprenorphine initiation * Use of methadone as long acting opioid (due to prolonged half-life and limited data in other populations) * Use of illicit drugs as documented by urine toxicology screen (except for THC) * Pregnancy * Acute or severe bronchial asthma * Hypersensitivity to buprenorphine or any component of the product * Medical disorder, condition, or history that in the investigator's judgement would impair the patient's ability to participate or complete this study or render the patient to be inappropriate for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment | 72 hours after buprenorphine initiation | Data will be collected on need for hospitalization within 72 hours of conversion due to withdrawal induced vaso-occlusive crisis (VOC). If 2 out of the first 5 patients require hospitalization within 72 hours of conversion the study will be stopped and we will assess what changes need to be made in the protocol to decrease the risk of hospitalization triggered by the conversion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Acute Care Visits Per Subject in the 6 Months Prior to Buprenorphine (BUP) Induction and in the 6 Months Post to BUP Induction | 6 months pre BUP induction, 6 months post BUP induction | Change in the number of acute care visits per subject in the 6 months prior to BUP induction and in the 6 months post to BUP induction will be observed by comparing the mean number of acute care visits per patient- either to Emergency Department (ED) or to Sickle Cell Infusion Center - in the six months prior to BUP induction and in the six months post to BUP induction. |
| Change in Severity of Opiate Withdrawal, Based on the Clinical Opiate Withdrawal Scale (COWS) Score | COWS score at BUP induction, COWS score at the end of the first day of induction | Change in severity of opiate withdrawal will be observed by comparing the mean COWS score at BUP induction and 1 day post induction. All patients will be in opiate withdrawal at the time of buprenorphine induction and at the end of the first day of induction. The level of withdrawal will be measured by the COWS score, an 11-item scale designed to be administered by a clinician. The score ranges from 0-4 (no withdrawal), 5-12 (mild withdrawal), 13-24 (moderate withdrawal), 25-36 (severe withdrawal), and 36-48 (most severe withdrawal). |
| Number of Participants Continuing Buprenorphine Therapy After 6 Months of Induction | 6 months after induction | After induction, clinical team will continue to follow up with patients to see if they would like to continue buprenorphine therapy during the next 6 months after induction. The date of discontinuation and the reason why will be recorded. The number of participants reported in the outcome is the number of participants that continued buprenorphine therapy 6 months after induction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buprenorphine Arm This is the main and only arm of the study. All patients in this arm will undergo the steps outlined in the protocol to convert to buprenorphine treatment.
buprenorphine: Patients in this study will receive dosages to be determined by a physician that are specific to each patient. | 47 |
| Total | 47 |
Baseline characteristics
| Characteristic | Buprenorphine Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants |
| Age, Continuous | 38 years STANDARD_DEVIATION 10.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 46 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 47 |
| other Total, other adverse events | 9 / 47 |
| serious Total, serious adverse events | 1 / 47 |
Outcome results
Primary
Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment
Data will be collected on need for hospitalization within 72 hours of conversion due to withdrawal induced vaso-occlusive crisis (VOC). If 2 out of the first 5 patients require hospitalization within 72 hours of conversion the study will be stopped and we will assess what changes need to be made in the protocol to decrease the risk of hospitalization triggered by the conversion.
Time frame: 72 hours after buprenorphine initiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buprenorphine Arm | Number of Subjects Who Require Hospitalization Within 72 Hours Post Conversion From Full Agonist Opioids to Buprenorphine-based Pain Treatment | 1 Participants |
Secondary
Change in Severity of Opiate Withdrawal, Based on the Clinical Opiate Withdrawal Scale (COWS) Score
Change in severity of opiate withdrawal will be observed by comparing the mean COWS score at BUP induction and 1 day post induction. All patients will be in opiate withdrawal at the time of buprenorphine induction and at the end of the first day of induction. The level of withdrawal will be measured by the COWS score, an 11-item scale designed to be administered by a clinician. The score ranges from 0-4 (no withdrawal), 5-12 (mild withdrawal), 13-24 (moderate withdrawal), 25-36 (severe withdrawal), and 36-48 (most severe withdrawal).
Time frame: COWS score at BUP induction, COWS score at the end of the first day of induction
Population: 38 out of 43 patients had complete pre-induction COWS data 37 out of 43 patients had complete post-induction COWS data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buprenorphine Arm | Change in Severity of Opiate Withdrawal, Based on the Clinical Opiate Withdrawal Scale (COWS) Score | COWS score at BUP induction | 8.92 score on a scale | Standard Deviation 3.8 |
| Buprenorphine Arm | Change in Severity of Opiate Withdrawal, Based on the Clinical Opiate Withdrawal Scale (COWS) Score | COWS score at the end of the first day of induction | 3.32 score on a scale | Standard Deviation 2.46 |
Secondary
Change in the Number of Acute Care Visits Per Subject in the 6 Months Prior to Buprenorphine (BUP) Induction and in the 6 Months Post to BUP Induction
Change in the number of acute care visits per subject in the 6 months prior to BUP induction and in the 6 months post to BUP induction will be observed by comparing the mean number of acute care visits per patient- either to Emergency Department (ED) or to Sickle Cell Infusion Center - in the six months prior to BUP induction and in the six months post to BUP induction.
Time frame: 6 months pre BUP induction, 6 months post BUP induction
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buprenorphine Arm | Change in the Number of Acute Care Visits Per Subject in the 6 Months Prior to Buprenorphine (BUP) Induction and in the 6 Months Post to BUP Induction | Number of Acute Visits per patient 6 months prior to BUP induction | 11.86 acute care visits per patient | Standard Deviation 11.92 |
| Buprenorphine Arm | Change in the Number of Acute Care Visits Per Subject in the 6 Months Prior to Buprenorphine (BUP) Induction and in the 6 Months Post to BUP Induction | Number of Acute Visits per patient 6 months post BUP induction | 3.35 acute care visits per patient | Standard Deviation 3.79 |
Secondary
Number of Participants Continuing Buprenorphine Therapy After 6 Months of Induction
After induction, clinical team will continue to follow up with patients to see if they would like to continue buprenorphine therapy during the next 6 months after induction. The date of discontinuation and the reason why will be recorded. The number of participants reported in the outcome is the number of participants that continued buprenorphine therapy 6 months after induction.
Time frame: 6 months after induction
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buprenorphine Arm | Number of Participants Continuing Buprenorphine Therapy After 6 Months of Induction | 38 Participants |