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Slow recruitment
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Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. The investigators are interested in investigating the efficacy of dipyridamole in preventing flares in patients with lupus and its impact on biomarkers of disease activity.
T cells in systemic lupus erythematosus (SLE) express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in combination with low dose aspirin in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. The investigators aim to investigate the efficacy of dipyridamole in the prevention of flares in SLE patients after withdrawal of background immunosuppressive medications. The investigators will additionally evaluate the safety and tolerability of dipyridamole and its impact on quality of life measures in this population. Furthermore, the effect of dipyridamole on T and B cell biomarkers will be examined.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| extended release dipyridamole/aspirin | Experimental | extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks |
|
| aspirin | Active Comparator | half a tablet of a 81mg aspirin twice daily for 24 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| extended release dipyridamole 200mg/aspirin 25mg | Drug | one tablet twice daily for 24 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA) | This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Systemic Lupus Erythematosus Responder Index (SRI) 4 | This is a landmark analysis of percentage of patients who meet the following response criteria: Compared to baseline there must be a 4 point decrease in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), no increase in The British Isles Lupus Assessment Group (BILAG) Index score and no more of an increase in Physician's Global Assessment (PGA) than 10% of the scale. As assessed here, there must also be no off protocol increase in medications. All scales signify worsening disease when scores increase. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Katherine Thanou, MD | Oklahoma Medical Research Foundation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oklahoma Medical Research Foundation | Oklahoma City | Oklahoma | 73104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21437870 | Background | Kyttaris VC, Zhang Z, Kampagianni O, Tsokos GC. Calcium signaling in systemic lupus erythematosus T cells: a treatment target. Arthritis Rheum. 2011 Jul;63(7):2058-66. doi: 10.1002/art.30353. | |
| 33687069 | Derived | Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2. |
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Those who wish access to this data may contact Joan Merrill at joan-merrill@omrf.org for further information
The data will be available on or before June 1 2021
For de-identified data only: Please submit a two page request describing the research you wish to do and the investigators credentials and current employment. This will be reviewed by our cohort advisory board and IRB prior to release.
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There were no pre-assignment restrictions or procedures.
All patients were recruited from the Oklahoma Medical Research Foundation clinic after a full informed consent process.
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| ID | Title | Description |
|---|---|---|
| FG000 | Extended Release Dipyridamole/Aspirin | extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks extended release dipyridamole 200mg/aspirin 25mg: one tablet twice daily for 24 weeks |
| FG001 | Aspirin | half a tablet of a 81mg aspirin twice daily for 24 weeks 81mg aspirin: half a tablet twice daily for 24 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Extended Release Dipyridamole/Aspirin | extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks extended release dipyridamole 200mg/aspirin 25mg: one tablet twice daily for 24 weeks |
| BG001 | Aspirin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA) | This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76. | Full Analysis Set was analyzed including all randomized patients | Posted | Count of Participants | Participants | 24 weeks |
6 months
All adverse events were recorded in the medical record and compiled for analysis.
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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 | Extended Release Dipyridamole/Aspirin | extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks extended release dipyridamole 200mg/aspirin 25mg: one tablet twice daily for 24 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hysterectomy | Reproductive system and breast disorders | MedDRA (10.0) | Non-systematic Assessment | This patient had sudden schedule change for non-emergent hysterectomy during the trial. Intubation was complicated by pneumonia but that did not prolong hospitalization (reported as non serious AE). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joan T. Merrill, M.D. | Oklahoma Medical Research Foundation | 405-822-2336 | joan-merrill@omrf.org |
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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 | Jan 13, 2015 | Oct 9, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| D000068342 | Aspirin, Dipyridamole Drug Combination |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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Pilot study
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| 81mg aspirin | Drug | half a tablet twice daily for 24 weeks |
|
|
| 24 weeks |
| SRI Component Analyses: 4 Point Drop in SLEDAI | This is a landmark analysis of percentage of patients who, compared to baseline, have a 4 point drop in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A 4 point decrease signifies a clinically significant decrease in disease activity as reported in many studies and as commonly used as a clinical endpoint in trials. SLEDAI could range 0-105 but is rarely greater than 20. | 24 weeks |
half a tablet of a 81mg aspirin twice daily for 24 weeks
81mg aspirin: half a tablet twice daily for 24 weeks
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mean BILAG Score at Entry | The BILAG (Britiish Isles Lupus Assessment Group) index is commonly used in international SLE trials. It provides a discontinuous scale that assigns a score to each active organ system based on assessment of disease as mild (BILAG C) moderate (B) or severe (A). A global score is derived by assigning 12 points to each organ rated severe (A) 8 points for moderate (B) and 1 point for mild (C), adding these together. Thus, the total score is weighted by the severity of disease in each organ. Mean population scores at baseline are calculated for each group. | Mean | Standard Deviation | units on a scale |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Extended Release Dipyridamole/Aspirin | extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks extended release dipyridamole 200mg/aspirin 25mg: one tablet twice daily for 24 weeks |
| OG001 | Aspirin | half a tablet of a 81mg aspirin twice daily for 24 weeks 81mg aspirin: half a tablet twice daily for 24 weeks |
|
|
| Secondary | Systemic Lupus Erythematosus Responder Index (SRI) 4 | This is a landmark analysis of percentage of patients who meet the following response criteria: Compared to baseline there must be a 4 point decrease in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), no increase in The British Isles Lupus Assessment Group (BILAG) Index score and no more of an increase in Physician's Global Assessment (PGA) than 10% of the scale. As assessed here, there must also be no off protocol increase in medications. All scales signify worsening disease when scores increase. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76. | Full analysis set of all randomized patients | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| Secondary | SRI Component Analyses: 4 Point Drop in SLEDAI | This is a landmark analysis of percentage of patients who, compared to baseline, have a 4 point drop in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A 4 point decrease signifies a clinically significant decrease in disease activity as reported in many studies and as commonly used as a clinical endpoint in trials. SLEDAI could range 0-105 but is rarely greater than 20. | Full Analysis Set of all randomized patients | Posted | Count of Participants | Participants | 24 weeks |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 13 |
| 13 |
| EG001 | Aspirin | half a tablet of a 81mg aspirin twice daily for 24 weeks 81mg aspirin: half a tablet twice daily for 24 weeks | 0 | 5 | 1 | 5 | 5 | 5 |
|
| Upper Respiratory Infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment | Described as several dizzy spells with two episodes of near fainting or fainting |
|
| Spider Bite | Injury, poisoning and procedural complications | MedDRA (10.0) | Non-systematic Assessment |
|
| Bladder Outlet Obstruction | Renal and urinary disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Chlamydia infectoin | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| herpes zoster | Immune system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Muscle Cramp | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
| neuralgia | Immune system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Sleep Disorder | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment | At two different points in the study patient experienced insomnia and hypersomulence |
|
| urticaria | Immune system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| sprained ankle | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| weight loss | General disorders | MedDRA (10.0) | Non-systematic Assessment | This was not associated with anorexia reported by patient but no cause found. It continued for a number of weeks but did was not reported to continue after that |
|
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| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004176 | Dipyridamole |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |