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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Buprenorphine Arm | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| buprenorphine | Drug | Patients in this study will receive dosages to be determined by a physician that are specific to each patient. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 72 hours after buprenorphine initiation |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sophie Lanzkron, MD, MHS | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25220043 | Background | Daitch D, Daitch J, Novinson D, Frey M, Mitnick C, Pergolizzi J Jr. Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med. 2014 Dec;15(12):2087-94. doi: 10.1111/pme.12520. Epub 2014 Sep 12. | |
| 27320469 | Background |
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Data will be published at some point in the future but individual data will not be disclosed
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| ID | Title | Description |
|---|---|---|
| FG000 | Buprenorphine Arm | This is the main and only arm of the study. This was an observational trial in which patients who were converted to buprenorphine had data collected on hospital utilization before and after conversion to buprenorphine and filled out surveys listed in secondary outcomes. buprenorphine: As this was part of clinical care individual dosages were dependent on prior opioid exposure and patient characteristics. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | 72 hours after buprenorphine initiation |
|
Within 72 hours of induction
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Nervous system disorders | Systematic Assessment | Central Retinal Artery Occlusion- Thought unlikely to induction |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Opioid Withdrawal | Psychiatric disorders | Systematic Assessment | Participants with recurrent withdrawal who had their doses adjusted upward within two days. |
The study was not randomized nor controlled. The participant pool was limited to those patients who consented to have their data reported; and among those prospectively enrolled, to those who accepted induction. In addition, not all inductions followed the same procedure. In particular, those that were performed inpatient might have a number of biases in patient selection and capacity to detect adverse events.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sophie Lanzkron | Johns Hopkins University School of Medicine | 4105028642 | slanzkr@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 28, 2020 | Jul 8, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D000069479 | Buprenorphine, Naloxone Drug Combination |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| 6 months pre BUP induction, 6 months post BUP induction |
| 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). | COWS score at BUP induction, COWS score at the end of the first day of induction |
| 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. | 6 months after induction |
| Carroll CP, Lanzkron S, Haywood C Jr, Kiley K, Pejsa M, Moscou-Jackson G, Haythornthwaite JA, Campbell CM. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease. Am J Prev Med. 2016 Jul;51(1 Suppl 1):S69-77. doi: 10.1016/j.amepre.2016.02.012. |
| 1710777 | Background | Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 4;325(1):11-6. doi: 10.1056/NEJM199107043250103. |
| 12924748 | Background | Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| 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. | Posted | Mean | Standard Deviation | acute care visits per patient | 6 months pre BUP induction, 6 months post BUP induction |
|
|
|
| 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). | 38 out of 43 patients had complete pre-induction COWS data 37 out of 43 patients had complete post-induction COWS data | Posted | Mean | Standard Deviation | score on a scale | COWS score at BUP induction, COWS score at the end of the first day of induction |
|
|
|
| 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. | Posted | Count of Participants | Participants | 6 months after induction |
|
|
|
| 0 |
| 47 |
| 1 |
| 47 |
| 9 |
| 47 |
|
|
| Body Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Participant presented with worsened pain. Participant reported pain crisis after uneventful induction. |
|
| Neck Swelling | General disorders | Systematic Assessment | participant who presented with neck swelling |
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| Tongue numbness | General disorders | Systematic Assessment | participant experienced tongue numbness during induction |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Participant was admitted to the hospital for pneumonia and suspicion of delayed type hemolytic transfusion reaction related to a prior transfusion |
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| Headache | General disorders | Systematic Assessment | participant had headache during induction |
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| Hyperglycemia | Endocrine disorders | Systematic Assessment | participant with brittle type I diabetes mellitus and poor insulin adherence presenting with hyperglycemia as was typical of many prior episodes |
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| Nausea | Gastrointestinal disorders | Systematic Assessment | participant with brittle type I diabetes mellitus and poor insulin adherence presenting with nausea as was typical of many prior episodes |
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D009270 | Naloxone |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
|