Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)
Summary
The purpose of this study is: 1. To assess the efficacy of a lipid-lowering agent (atorvastatin) on the development of atherosclerosis that predisposes children with SLE to cardiovascular events in adulthood. 2. To assess the safety of intermediate-term (36 months) treatment of children and young adults with atorvastatin. 3. To further characterize the course of SLE in children and young adults, by establishing a cohort of pediatric SLE patients to be followed prospectively. 4. To establish a mechanism for conducting clinical trials in rare pediatric rheumatic diseases using the Children's Arthritis and Rheumatology Research Alliance (CARRA).
Timeline
- Start
- 2003-09
- Primary completion
- 2009-12
- Completion
- 2009-12
Outcome
Missed primary endpoint
paper The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met PMID 23436914 ↗
paper Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). PMID 22031171 ↗
Publications
- Gurion R, Tangpricha V, Yow E, Schanberg LE, McComsey GA, Robinson AB; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Avascular necrosis in pediatric systemic lupus erythematosus: a brief report and review of the literature. Pediatr Rheumatol Online J. 2015 Apr 23;13:13. doi: 10.1186/s12969-015-0008-x.
- Robinson AB, Tangpricha V, Yow E, Gurion R, Schanberg LE, McComsey GA; APPLE Investigators. Vitamin D status is a determinant of atorvastatin effect on carotid intima medial thickening progression rate in children with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) substudy. Lupus Sci Med. 2014 Sep 10;1(1):e000037. doi: 10.1136/lupus-2014-000037. eCollection 2014.
- Robinson AB, Tangpricha V, Yow E, Gurion R, McComsey GA, Schanberg LE; APPLE Investigators. Vitamin D deficiency is common and associated with increased C-reactive protein in children and young adults with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus substudy. Lupus Sci Med. 2014 Apr 30;1(1):e000011. doi: 10.1136/lupus-2014-000011. eCollection 2014.
- Ardoin SP, Schanberg LE, Sandborg CI, Barnhart HX, Evans GW, Yow E, Mieszkalski KL, Ilowite NT, Eberhard A, Imundo LF, Kimura Y, Levy D, von Scheven E, Silverman E, Bowyer SL, Punaro L, Singer NG, Sherry DD, McCurdy DK, Klein-Gitelman M, Wallace C, Silver RM, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed AM, Thompson SD; APPLE investigators. Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein. Ann Rheum Dis. 2014 Mar;73(3):557-66. doi: 10.1136/annrheumdis-2012-202315. Epub 2013 Feb 22.
- Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, Mieszkalski KL, Ilowite NT, Eberhard A, Imundo LF, Kimura Y, von Scheven E, Silverman E, Bowyer SL, Punaro M, Singer NG, Sherry DD, McCurdy D, Klein-Gitelman M, Wallace C, Silver R, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed AM, Provenzale J, Thompson SD; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Use of atorvastatin in systemic lupus erythematosus in children and adolescents. Arthritis Rheum. 2012 Jan;64(1):285-96. doi: 10.1002/art.30645.
- Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, Mieszkalski KL, Ilowite NT, Eberhard A, Levy DM, Kimura Y, von Scheven E, Silverman E, Bowyer SL, Punaro L, Singer NG, Sherry DD, McCurdy D, Klein-Gitelman M, Wallace C, Silver R, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed A; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. Arthritis Rheum. 2009 May;60(5):1496-507. doi: 10.1002/art.24469.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Atorvastatin | Small molecule | 10 mg | Oral |
| Subject | Atorvastatin | Small molecule | 20 mg | Oral |