Trial Outcomes & Findings for Effects of Fluvastatin on Proinflammatory and Prothrombotic Markers in Antiphospholipid Syndrome Patients (NCT NCT00674297)

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

3 months

Results posted on

2018-05-01

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	PAPS Primary APS	SLE/APS SLE with APS	Primary aPL Persistant aPL positivity without SLE or APS.	SLE/aPL Persistent aPL positivity with SLE but no APS.
Overall Study STARTED	18	7	9	7
Overall Study COMPLETED	8	7	5	4
Overall Study NOT COMPLETED	10	0	4	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of Fluvastatin on Proinflammatory and Prothrombotic Markers in Antiphospholipid Syndrome Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluvastatin n=41 Participants All patients will take Fluvastatin 40 mg daily for 3 months. Fluvastatin: Fluvastatin 40 mg daily for 3 months
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	28 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	PAPS n=18 Participants Primary APS	SLE/APS n=7 Participants SLE with APS	Primary aPL n=9 Participants Persistant aPL positivity without SLE or APS.	SLE/aPL n=7 Participants Persistent aPL positivity with SLE but no APS.
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker IL6	31.2 pg/mL Standard Deviation 48.4	12.2 pg/mL Standard Deviation 103.5	0.4 pg/mL Standard Deviation 0.7	2.7 pg/mL Standard Deviation 76.8
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker IL1B	3.0 pg/mL Standard Deviation 7.7	11.4 pg/mL Standard Deviation 20.1	0.3 pg/mL Standard Deviation 0.6	0.5 pg/mL Standard Deviation 5.1
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker IL8	24.5 pg/mL Standard Deviation 48.4	27.4 pg/mL Standard Deviation 53.7	7.2 pg/mL Standard Deviation 50.4	21.6 pg/mL Standard Deviation 48.9
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker VEGF	242.2 pg/mL Standard Deviation 399.6	109.1 pg/mL Standard Deviation 348.4	74.6 pg/mL Standard Deviation 158.3	67.2 pg/mL Standard Deviation 499.4
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker TNFa	21.5 pg/mL Standard Deviation 50.5	11.6 pg/mL Standard Deviation 24.1	8.9 pg/mL Standard Deviation 15.7	53.9 pg/mL Standard Deviation 62.5
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker IFNa	10.1 pg/mL Standard Deviation 88.4	0.3 pg/mL Standard Deviation 367.1	0.3 pg/mL Standard Deviation 512.2	13.2 pg/mL Standard Deviation 558.5
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker IP10	427.2 pg/mL Standard Deviation 569.8	656.2 pg/mL Standard Deviation 454.8	249.7 pg/mL Standard Deviation 698.9	472.5 pg/mL Standard Deviation 690.5
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients Biomarker sCD40L	276.5 pg/mL Standard Deviation 676.0	145.6 pg/mL Standard Deviation 5159.8	149.7 pg/mL Standard Deviation 17035.6	76.9 pg/mL Standard Deviation 970.0

PRIMARY outcome

Timeframe: 3 months

Biomarker sTF (pM)

Outcome measures

Outcome measures
Measure	PAPS n=18 Participants Primary APS	SLE/APS n=7 Participants SLE with APS	Primary aPL n=9 Participants Persistant aPL positivity without SLE or APS.	SLE/aPL n=7 Participants Persistent aPL positivity with SLE but no APS.
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients	153.6 pM Standard Deviation 381.0	329.2 pM Standard Deviation 447.0	190.4 pM Standard Deviation 139.0	102.1 pM Standard Deviation 177.0

PRIMARY outcome

Timeframe: 3 months

Biomarkers sICAM-1 (ng/mL), sVCAM-1 (ng/mL), sE-sel (ng/mL)

Outcome measures

Outcome measures
Measure	PAPS n=18 Participants Primary APS	SLE/APS n=7 Participants SLE with APS	Primary aPL n=9 Participants Persistant aPL positivity without SLE or APS.	SLE/aPL n=7 Participants Persistent aPL positivity with SLE but no APS.
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients sICAM-1	281.6 ng/mL Standard Deviation 406.8	55.1 ng/mL Standard Deviation 70.3	163.5 ng/mL Standard Deviation 341.7	2.8 ng/mL Standard Deviation 32.9
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients sVCAM-1	1128.4 ng/mL Standard Deviation 1152.8	156.4 ng/mL Standard Deviation 19.3	321.3 ng/mL Standard Deviation 1015.1	41.1 ng/mL Standard Deviation 27.2
Effects of Fluvastatin on Proinflammatory and Prothrombotic Biomarkers (BMR) in aPL Positive Patients sE-sel	27.7 ng/mL Standard Deviation 36.7	14.7 ng/mL Standard Deviation 20.4	10.9 ng/mL Standard Deviation 26.4	4.1 ng/mL Standard Deviation 21.5

Adverse Events

aPL Positive Patients

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	aPL Positive Patients n=41 participants at risk Patients with aPL positivity
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 1/41 • Number of events 1 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.
Immune system disorders Lupus flare	2.4% 1/41 • Number of events 1 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.
Musculoskeletal and connective tissue disorders Myalgia with high CPK	2.4% 1/41 • Number of events 1 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.
Musculoskeletal and connective tissue disorders Myalgia with normal CPK	7.3% 3/41 • Number of events 3 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.
Vascular disorders Recurrent deep vein thrombosis	2.4% 1/41 • Number of events 1 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.
Nervous system disorders Headache	2.4% 1/41 • Number of events 1 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.
Psychiatric disorders Insomnia	2.4% 1/41 • Number of events 1 • 6 months An adverse event (AE) was defined as any untoward medical occurrence in a study patient regardless of causality assessment. A serious AE was defined as one occurring at any dose that met one or more of the following criteria: death; life-threatening; requiring or prolonging inpatient hospitalisation; disabling; or resulting in a congenital anomaly/birth defect.

Additional Information

Doruk Erkan, MD

Hospital for Special Surgery

Phone: 212 774-2291

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place