Antiphospholipid Syndrome
Conditions
Keywords
Persistently Antiphospholipid Antibody Positive Patients
Brief summary
The purpose of this study is to determine whether a drug named Fluvastatin is beneficial and safe in reducing the risk of cardiovascular disease and blood clots in patients with antiphospholipid antibodies or Antiphospholipid Syndrome (APS).
Detailed description
The primary objective of the study is to determine the effects of fluvastatin on pro-thrombotic and pro-inflammatory markers in aPL-positive lupus and non-lupus patients (primary endpoint) and to determine the safety of fluvastatin in aPL-positive lupus and non-lupus patients (secondary endpoint). All eligible patients will sign an IRB-approved consent form during the screening visit and give blood for baseline laboratory tests. Within a week of the screening visit, all patients will be started on Fluvastatin 40 mg daily for three months. At three months patients will be instructed to stop the study medication and they will be followed for another three months. Thus, the total duration of the study is six months: first three months is interventional and the last three months is observational.
Interventions
DRUGFluvastatin
Fluvastatin 40 mg daily for 3 months
Sponsors
University of Texas
Hospital for Special Surgery, New York
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Persistently antiphospholipid-antibody positive patients (positive lupus anticoagulant test, anticardiolipin antibody ≥ 40 GPL /MPL, and/or anti- β2-glycoprotein I antibody \> 20 SGU/SMU) with or without systemic lupus erythematosus
Exclusion criteria
* Younger than 18 year-old * Pregnant * Planning to get pregnant within the next 6 months * Taking other cholesterol lowering agents * Taking other immunosuppressive medications (such as methotrexate, azathioprine, cellcept, enbrel, remicade, or rituximab)(Hydroxychloroquine \[Plaquenil\] during the study period is allowed). * Treatment with biologic agents including anti-TNF medications and Rituximab * Treatment with erythromycin, itraconazole, or clarithromycin * Taking prednisone higher than 10 mg daily * Taking non-steroidal anti-inflammatory drug (such as Motrin, Advil, etc) regularly * Have a muscle or liver disease * Have chronic renal disease requiring dialysis * Have hepatitis C and/or HIV infection * Have active infections requiring antibiotics * Have the diagnosis of a systemic autoimmune disease (such as rheumatoid arthritis or systemic sclerosis) other than lupus * Have diagnosis of another chronic condition requiring corticosteroid treatment more than 10mg daily * History of an allergic reaction to cholesterol lowering agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | 3 months | Biomarkers: IL6 (pg/mL), IL1β (pg/mL), IL8 (pg/mL), VEGF (pg/mL), TNFα (pg/mL), IFNα (pg/mL), IP10 (pg/mL), sCD40L (pg/mL) |
Countries
United States
Participant flow
Recruitment details
4 groups were recruited: primary antiphospholipid syndrome(PAPS); systemic lupus erythematosus (SLE) with antiphospholipid syndrome(APS)(SLE/APS); persistent aPL positivity without SLE/APS(Primary aPL); and persistent aPL positivity with SLE but no APS(SLE/ aPL). The frequency-matched control group was identified from a databank of healthy persons.
Pre-assignment details
SLE was defined based on the American College of Rheumatology classification criteria. APS was defined based on the updated Sapporo classification criteria. Positive aPL was defined as persistently (at least 12 weeks apart) positive LA test, aCL≥40 GPL/MPL and/or aβ2GPI≥20 SGU/SMU.
Participants by arm
| Arm | Count |
|---|---|
| Fluvastatin All patients will take Fluvastatin 40 mg daily for 3 months.
Fluvastatin: Fluvastatin 40 mg daily for 3 months | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Fluvastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants |
| Race/Ethnicity, Customized Caucasian | 28 Participants |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 41 |
| other Total, other adverse events | 8 / 41 |
| serious Total, serious adverse events | 0 / 41 |
Outcome results
Primary
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients
Biomarkers: IL6 (pg/mL), IL1β (pg/mL), IL8 (pg/mL), VEGF (pg/mL), TNFα (pg/mL), IFNα (pg/mL), IP10 (pg/mL), sCD40L (pg/mL)
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker TNFa | 21.5 pg/mL | Standard Deviation 50.5 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL6 | 31.2 pg/mL | Standard Deviation 48.4 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IFNa | 10.1 pg/mL | Standard Deviation 88.4 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL1B | 3.0 pg/mL | Standard Deviation 7.7 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IP10 | 427.2 pg/mL | Standard Deviation 569.8 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL8 | 24.5 pg/mL | Standard Deviation 48.4 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker VEGF | 242.2 pg/mL | Standard Deviation 399.6 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker sCD40L | 276.5 pg/mL | Standard Deviation 676 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IFNa | 0.3 pg/mL | Standard Deviation 367.1 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IP10 | 656.2 pg/mL | Standard Deviation 454.8 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker sCD40L | 145.6 pg/mL | Standard Deviation 5159.8 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL6 | 12.2 pg/mL | Standard Deviation 103.5 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker TNFa | 11.6 pg/mL | Standard Deviation 24.1 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL1B | 11.4 pg/mL | Standard Deviation 20.1 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL8 | 27.4 pg/mL | Standard Deviation 53.7 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker VEGF | 109.1 pg/mL | Standard Deviation 348.4 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IP10 | 249.7 pg/mL | Standard Deviation 698.9 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL8 | 7.2 pg/mL | Standard Deviation 50.4 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL6 | 0.4 pg/mL | Standard Deviation 0.7 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker sCD40L | 149.7 pg/mL | Standard Deviation 17035.6 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IFNa | 0.3 pg/mL | Standard Deviation 512.2 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker VEGF | 74.6 pg/mL | Standard Deviation 158.3 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker TNFa | 8.9 pg/mL | Standard Deviation 15.7 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL1B | 0.3 pg/mL | Standard Deviation 0.6 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker sCD40L | 76.9 pg/mL | Standard Deviation 970 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker TNFa | 53.9 pg/mL | Standard Deviation 62.5 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL6 | 2.7 pg/mL | Standard Deviation 76.8 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL1B | 0.5 pg/mL | Standard Deviation 5.1 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IL8 | 21.6 pg/mL | Standard Deviation 48.9 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IFNa | 13.2 pg/mL | Standard Deviation 558.5 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker IP10 | 472.5 pg/mL | Standard Deviation 690.5 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | Biomarker VEGF | 67.2 pg/mL | Standard Deviation 499.4 |
Primary
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients
Biomarker sTF (pM)
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | 153.6 pM | Standard Deviation 381 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | 329.2 pM | Standard Deviation 447 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | 190.4 pM | Standard Deviation 139 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | 102.1 pM | Standard Deviation 177 |
Primary
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients
Biomarkers sICAM-1 (ng/mL), sVCAM-1 (ng/mL), sE-sel (ng/mL)
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sE-sel | 27.7 ng/mL | Standard Deviation 36.7 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sICAM-1 | 281.6 ng/mL | Standard Deviation 406.8 |
| PAPS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sVCAM-1 | 1128.4 ng/mL | Standard Deviation 1152.8 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sICAM-1 | 55.1 ng/mL | Standard Deviation 70.3 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sE-sel | 14.7 ng/mL | Standard Deviation 20.4 |
| SLE/APS | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sVCAM-1 | 156.4 ng/mL | Standard Deviation 19.3 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sVCAM-1 | 321.3 ng/mL | Standard Deviation 1015.1 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sICAM-1 | 163.5 ng/mL | Standard Deviation 341.7 |
| Primary aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sE-sel | 10.9 ng/mL | Standard Deviation 26.4 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sICAM-1 | 2.8 ng/mL | Standard Deviation 32.9 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sE-sel | 4.1 ng/mL | Standard Deviation 21.5 |
| SLE/aPL | Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients | sVCAM-1 | 41.1 ng/mL | Standard Deviation 27.2 |