Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)

• Sponsor: Laura Schanberg (Other)
• Overall Status: Completed
• CT.gov ID: NCT00065806
• Collaborator: (none)
• Enrollment: 221
• Location: 1
• Arms: 2
• Duration (Months): 75
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Lupus Erythematosus, Systemic	Drug: Atorvastatin; Drug: Placebo atorvastatin	Phase 3

Detailed Description

Children and adolescents with SLE represent 15% of all SLE patients. Children with SLE suffer high morbidity that affects many organ systems, reduces their quality of life, and shortens their lifespan. As more children with SLE survive into adulthood, atherosclerotic cardiovascular disease has emerged as a major concern. SLE is a significant risk factor for myocardial infarction and death in young premenopausal women with SLE, even after controlling for traditional cardiovascular risk factors. Acceleration of atherogenesis in SLE most likely reflects SLE-associated vascular immune and inflammatory changes.

Although limited, the data on cardiovascular and lipid abnormalities in children with SLE implicate atherosclerosis as an important cause of long-term morbidity and mortality. The 3-hydroxy-3-methlglutaryl-coenzyme A (HMG CoA) reductase inhibitors, or statins, reduce mortality and morbidity from atherosclerosis in adults and have intrinsic anti-inflammatory and immune modulatory properties. These anti-inflammatory and immune modulatory activities may have particular benefit in the prevention and treatment of atherosclerosis in SLE. This trial will evaluate atorvastatin in children with SLE in the largest cohort of pediatric SLE patients ever studied prospectively.

Children in this study will be randomized to receive either atorvastatin or a placebo. All children will be followed for 3 years, during which they will have 15 study visits. Study visits will generally last 2 hours and will include medical interview, medication review and pill count, physical examination, and blood and urine tests. Cardiovascular-specific outcome measures will include assessments of high sensitivity CRP; fasting lipid profile; homocysteine level; apolipoprotein A, B1, and Lp(a); carotid intima media thickness (IMT); and tensor diffusion/MRI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Test the Safety and Efficacy of Lipitor (Atorvastatin) in Reducing the Progression of Carotid IMT in Early Childhood SLE
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.	Drug: Atorvastatin; Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.; Other Names: Lipitor Atorvastatin Calcium
Placebo Comparator: 2 Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.	Drug: Placebo atorvastatin; Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.

Outcome Measures

Primary Outcome Measures

1. Change in Mean-Mean Common Carotid IMT (CIMT) [Change from baseline to 36 months]

   For the common carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right common near wall mean, right common far wall mean, left common near wall mean and left common far wall mean). These summary variables were then averaged to estimate a single mean-mean common CIMT for each participant visit.

Secondary Outcome Measures

1. Change in Mean-Max CIMT [Change from baseline to 36 months]

   For each side, segment and wall, the maximum CIMT over the 4 angles of interrogation was selected to produce 12 summary variables (right common near wall max, right common far wall max, right bifurcation near wall max, right bifurcation far wall max, right internal near wall max, right internal far wall max, left common near wall max, left common far wall max, left bifurcation near wall max, left bifurcation far wall max, left internal near wall max and left internal far wall max). These 12 summary variables were then averaged to estimate a single mean-max CIMT for each participant visit.

2. Change in Mean-Mean CIMT [Change from baseline to 36 months]

   For each side, segment and wall, mean CIMT values were averaged over the 4 angles of interrogation to produce 12 summary variables (right common near wall mean, right common far wall mean, right bifurcation near wall mean, right bifurcation far wall mean, right internal near wall mean, right internal far wall mean, left common near wall mean, left common far wall mean, left bifurcation near wall mean, left bifurcation far wall mean, left internal near wall mean and left internal far wall mean). These 12 summary variables were then averaged to estimate a single mean-mean CIMT for each participant visit.

3. Change in Mean-Max Common CIMT [Change from baseline to 36 months]

   For each side and wall of the common carotid arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right common near wall max, right common far wall max, left common near wall max and left common far wall max). These summary variables were then averaged to estimate a single mean-max common CIMT for each participant visit.

4. Change in Mean-Max Internal CIMT [Change from baseline to 36 months]

   For each side and wall of the internal carotid arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right internal near wall max, right internal far wall max, left internal near wall max and left internal far wall max). These summary variables were then averaged to estimate a single mean-max internal CIMT for each participant visit.

5. Change in Mean-Mean Internal CIMT [Change from baseline to 36 months]

   For the internal carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right internal near wall mean, right internal far wall mean, left internal near wall mean and left internal far wall mean). These summary variables were then averaged to estimate a single mean-mean internal CIMT for each participant visit.

6. Change in Mean-Max Bifurcation CIMT [Change from baseline to 36 months]

   For each side and wall of the bifurcation arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right bifurcation near wall max, right bifurcation far wall max, left bifurcation near wall max and left bifurcation far wall max). These summary variables were then averaged to estimate a single mean-max bifurcation CIMT for each participant visit.

7. Change in Mean-Mean Bifurcation CIMT [Change from baseline to 36 months]

   For the bifurcation arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right bifurcation near wall mean, right bifurcation far wall mean, left bifurcation near wall mean and left bifurcation far wall mean). These summary variables were then averaged to estimate a single mean-mean bifurcation CIMT for each participant visit.

8. Change in Mean-Max Far Wall CIMT [Change from baseline to 36 months]

   For the far wall measurements for each side and segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 6 summary variables (right common far wall max, right bifurcation far wall max, right internal far wall max, left common far wall max, left bifurcation far wall max, and left internal far wall max). These 6 summary variables were then averaged to estimate a single mean-max far wall CIMT for each participant visit.

9. Change in Mean-Mean Far Wall CIMT [Change from baseline to 36 months]

   For the far wall measurements for each side and segment, mean CIMT values were averaged over the 4 angles of interrogation to produce 6 summary variables (right common far wall mean, right bifurcation far wall mean, right internal far wall mean, left common far wall mean, left bifurcation far wall mean and left internal far wall mean). These 6 summary variables were then averaged to estimate a single mean-mean far wall CIMT for each participant visit.

10. Change in Mean-Max Near Wall CIMT [Change from baseline to 36 months]

    For the near wall measurements for each side and segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 6 summary variables (right common near wall max, right bifurcation near wall max, right internal near wall max, left common near wall max, left bifurcation near wall max, and left internal near wall max). These 6 summary variables were then averaged to estimate a single mean-max near wall CIMT for each participant visit.

11. Change in Mean-Mean Near Wall CIMT [Change from baseline to 36 months]

    For the near wall measurements for each side and segment, mean CIMT values were averaged over the 4 angles of interrogation to produce 6 summary variables (right common near wall mean, right bifurcation near wall mean, right internal near wall mean, left common near wall mean, left bifurcation wall mean and left internal far wall mean). These 6 summary variables were then averaged to estimate a single mean-mean far wall CIMT for each participant visit.

12. Change in Natural Log of mg/L for hsCRP [Change from baseline to 36 months]

13. Change in Total Cholesterol [Change from baseline to 36 months]

14. Change in HDL Cholesterol [Change from baseline to 36 months]

15. Change in LDL Cholesterol [Change from baseline to 36 months]

16. Change in Triglycerides [Change from baseline to 36 months]

17. Change in Lipoprotein A [Change from baseline to 36 months]

18. Change in Homocysteine [Change from baseline to 36 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meets American College of Rheumatology (ACR) revised diagnostic guidelines for SLE

• Weight of 25 kg (55 lbs) or more

• Outpatient

• Ability to complete self-report questionnaires in either English or Spanish

• Willingness to comply with recommended diet

• Acceptable methods of contraception

Exclusion Criteria:

• Drug-induced lupus

• Liver disease (ALT or aspartate aminotransferase greater than 2 X normal value)

• Myositis (CK greater than 3 X normal value)

• Inability to obtain adequate-quality IMT images

• Current use of oral or parenteral tacrolimus or cyclosporine

• Dialysis or serum creatinine reater than 2.5 mg/dL

• Active nephrotic syndrome (urinary protein greater than 3 g/24 h and serum albumin less than 2.3 g/dl)

• Total cholesterol greater than 350 mg/dL

• Xanthoma

• Familial hypercholesterolemia

• Pregnant or breastfeeding

• Use of estrogen-containing contraceptives (e.g., Lo-Ovral)

• Unable to adhere to study regimen

• Life-threatening non-SLE illness that would interfere with ability to complete the study

• Current drug or alcohol abuse

• Anticipated poor compliance

• Participation in another drug intervention study within 30 days of study enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Medical Center / Duke Clinical Research Institute	Durham	North Carolina	United States	27715

Sponsors and Collaborators

• Laura Schanberg

Investigators

• Principal Investigator: Laura E. Schanberg, MD, Duke Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Laura Schanberg, Associate Director, Professor, Duke University
• ClinicalTrials.gov Identifier: NCT00065806
• Other Study ID Numbers: Pro00006680; NIAMS-090; N01 AR022265
• First Posted: Aug 4, 2003
• Last Update Posted: Aug 15, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Laura Schanberg, Associate Director, Professor, Duke University: Pediatric lupus; Atherosclerosis; SLE; HMG CoA reductase inhibitor
• Additional relevant MeSH terms: Atherosclerosis; Lupus Erythematosus, Systemic; Atorvastatin

Study Results

Participant Flow

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Period Title: Overall Study
STARTED	113	108
COMPLETED	93	89
NOT COMPLETED	20	19

Baseline Characteristics

Arm/Group Title	1 Atorvastatin	2 Placebo	Total
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Total of all reporting groups
Overall Participants	113	108	221
Age (Count of Participants)
<=18 years	87 77%	87 80.6%	174 78.7%
Between 18 and 65 years	26 23%	21 19.4%	47 21.3%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.7 (2.8)	15.8 (2.5)	15.7 (2.6)
Sex: Female, Male (Count of Participants)
Female	95 84.1%	89 82.4%	184 83.3%
Male	18 15.9%	19 17.6%	37 16.7%

Outcome Measures

1. Primary Outcome

Title	Change in Mean-Mean Common Carotid IMT (CIMT)
Description	For the common carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right common near wall mean, right common far wall mean, left common near wall mean and left common far wall mean). These summary variables were then averaged to estimate a single mean-mean common CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0010	0.0024

2. Secondary Outcome

Title	Change in Mean-Max CIMT
Description	For each side, segment and wall, the maximum CIMT over the 4 angles of interrogation was selected to produce 12 summary variables (right common near wall max, right common far wall max, right bifurcation near wall max, right bifurcation far wall max, right internal near wall max, right internal far wall max, left common near wall max, left common far wall max, left bifurcation near wall max, left bifurcation far wall max, left internal near wall max and left internal far wall max). These 12 summary variables were then averaged to estimate a single mean-max CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0037	0.0064

3. Secondary Outcome

Title	Change in Mean-Mean CIMT
Description	For each side, segment and wall, mean CIMT values were averaged over the 4 angles of interrogation to produce 12 summary variables (right common near wall mean, right common far wall mean, right bifurcation near wall mean, right bifurcation far wall mean, right internal near wall mean, right internal far wall mean, left common near wall mean, left common far wall mean, left bifurcation near wall mean, left bifurcation far wall mean, left internal near wall mean and left internal far wall mean). These 12 summary variables were then averaged to estimate a single mean-mean CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0033	0.0049

4. Secondary Outcome

Title	Change in Mean-Max Common CIMT
Description	For each side and wall of the common carotid arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right common near wall max, right common far wall max, left common near wall max and left common far wall max). These summary variables were then averaged to estimate a single mean-max common CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0006	0.0008

5. Secondary Outcome

Title	Change in Mean-Max Internal CIMT
Description	For each side and wall of the internal carotid arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right internal near wall max, right internal far wall max, left internal near wall max and left internal far wall max). These summary variables were then averaged to estimate a single mean-max internal CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0090	0.0144

6. Secondary Outcome

Title	Change in Mean-Mean Internal CIMT
Description	For the internal carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right internal near wall mean, right internal far wall mean, left internal near wall mean and left internal far wall mean). These summary variables were then averaged to estimate a single mean-mean internal CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0067	0.0082

7. Secondary Outcome

Title	Change in Mean-Max Bifurcation CIMT
Description	For each side and wall of the bifurcation arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right bifurcation near wall max, right bifurcation far wall max, left bifurcation near wall max and left bifurcation far wall max). These summary variables were then averaged to estimate a single mean-max bifurcation CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0033	0.0072

8. Secondary Outcome

Title	Change in Mean-Mean Bifurcation CIMT
Description	For the bifurcation arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right bifurcation near wall mean, right bifurcation far wall mean, left bifurcation near wall mean and left bifurcation far wall mean). These summary variables were then averaged to estimate a single mean-mean bifurcation CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0030	0.0055

9. Secondary Outcome

Title	Change in Mean-Max Far Wall CIMT
Description	For the far wall measurements for each side and segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 6 summary variables (right common far wall max, right bifurcation far wall max, right internal far wall max, left common far wall max, left bifurcation far wall max, and left internal far wall max). These 6 summary variables were then averaged to estimate a single mean-max far wall CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0045	0.0082

10. Secondary Outcome

Title	Change in Mean-Mean Far Wall CIMT
Description	For the far wall measurements for each side and segment, mean CIMT values were averaged over the 4 angles of interrogation to produce 6 summary variables (right common far wall mean, right bifurcation far wall mean, right internal far wall mean, left common far wall mean, left bifurcation far wall mean and left internal far wall mean). These 6 summary variables were then averaged to estimate a single mean-mean far wall CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0042	0.0064

11. Secondary Outcome

Title	Change in Mean-Max Near Wall CIMT
Description	For the near wall measurements for each side and segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 6 summary variables (right common near wall max, right bifurcation near wall max, right internal near wall max, left common near wall max, left bifurcation near wall max, and left internal near wall max). These 6 summary variables were then averaged to estimate a single mean-max near wall CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0024	0.0038

12. Secondary Outcome

Title	Change in Mean-Mean Near Wall CIMT
Description	For the near wall measurements for each side and segment, mean CIMT values were averaged over the 4 angles of interrogation to produce 6 summary variables (right common near wall mean, right bifurcation near wall mean, right internal near wall mean, left common near wall mean, left bifurcation wall mean and left internal far wall mean). These 6 summary variables were then averaged to estimate a single mean-mean far wall CIMT for each participant visit.
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mm]	0.0022	0.0028

13. Secondary Outcome

Title	Change in Natural Log of mg/L for hsCRP
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [natural log of mg/L]	-0.13	0.27

14. Secondary Outcome

Title	Change in Total Cholesterol
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mg/dl]	-30.30	-0.72

15. Secondary Outcome

Title	Change in HDL Cholesterol
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mg/dl]	-0.43	0.89

16. Secondary Outcome

Title	Change in LDL Cholesterol
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mg/dl]	-27.63	-1.48

17. Secondary Outcome

Title	Change in Triglycerides
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mg/dl]	-11.04	-5.62

18. Secondary Outcome

Title	Change in Lipoprotein A
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [mg/dl]	2.00	6.34

19. Secondary Outcome

Title	Change in Homocysteine
Time Frame	Change from baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Atorvastatin	2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Measure Participants	113	108
Mean (95% Confidence Interval) [μmoles/liter]	1.84	1.76

Adverse Events

Arm/Group Title	1 Atorvastatin		2 Placebo
Arm/Group Description	Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Atorvastatin : Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.		Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months. Placebo atorvastatin : Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
All Cause Mortality
	1 Atorvastatin		2 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1 Atorvastatin		2 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/113 (30.1%)		40/108 (37%)
Blood and lymphatic system disorders
Thrombocytopenia	2/113 (1.8%)	3	1/108 (0.9%)	5
Thrombotic Thrombocytopenic Purpura	0/113 (0%)	0	1/108 (0.9%)	1
Cardiac disorders
Pericardial Effusion	1/113 (0.9%)	1	1/108 (0.9%)	1
Congenital, familial and genetic disorders
Sickle Cell Anaemia with Crisis	1/113 (0.9%)	5	1/108 (0.9%)	4
Gastrointestinal disorders
Abdominal Pain	1/113 (0.9%)	1	1/108 (0.9%)	1
Vomiting	1/113 (0.9%)	1	1/108 (0.9%)	1
Enteritis	1/113 (0.9%)	1	0/108 (0%)	0
Irritable Bowel Syndrome	1/113 (0.9%)	1	0/108 (0%)	0
Pancreatitis Acute	1/113 (0.9%)	1	0/108 (0%)	0
General disorders
Adverse Drug Reaction	1/113 (0.9%)	1	1/108 (0.9%)	1
Infusion Related Reaction	1/113 (0.9%)	1	0/108 (0%)	0
Non-Cardiac Chest Pain	0/113 (0%)	0	1/108 (0.9%)	1
Hepatobiliary disorders
Cholelithiasis	1/113 (0.9%)	1	0/108 (0%)	0
Hepatitis	0/113 (0%)	0	1/108 (0.9%)	1
Immune system disorders
Serum Sickness	0/113 (0%)	0	2/108 (1.9%)	2
Infections and infestations
Herpes Zoster	1/113 (0.9%)	1	5/108 (4.6%)	5
Pneumonia	4/113 (3.5%)	5	1/108 (0.9%)	5
Appendicitis	1/113 (0.9%)	1	1/108 (0.9%)	2
Gastroeneritis	2/113 (1.8%)	2	0/108 (0%)	0
Gastroenteritis Viral	2/113 (1.8%)	2	0/108 (0%)	0
Sinusitis	2/113 (1.8%)	2	0/108 (0%)	0
Viral Infection	2/113 (1.8%)	2	0/108 (0%)	0
Bacteraemia	0/113 (0%)	0	1/108 (0.9%)	1
Cervicitis Trichomonal	1/113 (0.9%)	1	0/108 (0%)	0
Clostridial Infection	0/113 (0%)	0	1/108 (0.9%)	1
Infection	0/113 (0%)	0	1/108 (0.9%)	1
Meningitis Aseptic	0/113 (0%)	0	1/108 (0.9%)	1
Meningitis Viral	0/113 (0%)	0	1/108 (0.9%)	1
Peritonitis Bacterial	1/113 (0.9%)	1	0/108 (0%)	0
Pharyngitis Streptococcal	1/113 (0.9%)	1	0/108 (0%)	0
Pneumonia Streptococcal	1/113 (0.9%)	1	0/108 (0%)	0
Pyelonephritis	0/113 (0%)	0	1/108 (0.9%)	1
Pyelonephritis Acute	0/113 (0%)	0	1/108 (0.9%)	1
Streptococcal Sepsis	1/113 (0.9%)	1	0/108 (0%)	0
Investigations
Muscle Enzyme Increased	1/113 (0.9%)	1	0/108 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/113 (0%)	0	2/108 (1.9%)	2
Gestational Diabetes	1/113 (0.9%)	1	0/108 (0%)	0
Musculoskeletal and connective tissue disorders
Systemic Lupus Erythematosus	10/113 (8.8%)	13	8/108 (7.4%)	10
Arthraligia	1/113 (0.9%)	1	0/108 (0%)	0
Myositis	1/113 (0.9%)	1	0/108 (0%)	0
Osteonecrosis	0/113 (0%)	0	1/108 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytosis haematophagic	0/113 (0%)	0	1/108 (0.9%)	1
Malignant Melanoma	0/113 (0%)	0	1/108 (0.9%)	1
Nervous system disorders
Convulsion	0/113 (0%)	0	3/108 (2.8%)	3
Headache	0/113 (0%)	0	1/108 (0.9%)	1
Migraine	0/113 (0%)	0	1/108 (0.9%)	1
Myelitis Transverse	0/113 (0%)	0	1/108 (0.9%)	1
Pregnancy, puerperium and perinatal conditions
Abortion, Spontaneous	1/113 (0.9%)	1	0/108 (0%)	0
Foetal Cardiac Disorder	1/113 (0.9%)	1	0/108 (0%)	0
Pre-eclampsia	1/113 (0.9%)	1	0/108 (0%)	0
Psychiatric disorders
Suicidal Ideation	1/113 (0.9%)	1	2/108 (1.9%)	2
Depression	2/113 (1.8%)	2	0/108 (0%)	0
Pscyhotic Disorder	0/113 (0%)	0	2/108 (1.9%)	2
Drug Dependence	1/113 (0.9%)	1	0/108 (0%)	0
Hallucination	0/113 (0%)	0	1/108 (0.9%)	1
Hallucination, Visual	0/113 (0%)	0	1/108 (0.9%)	1
Mental Status Changes	1/113 (0.9%)	1	0/108 (0%)	0
Lupus Encephalitis	1/113 (0.9%)	1	0/108 (0%)	0
Renal and urinary disorders
Lupus Nephritis	1/113 (0.9%)	1	3/108 (2.8%)	3
Glomerulonephritis Acute	1/113 (0.9%)	1	0/108 (0%)	0
Renal Failure Acute	1/113 (0.9%)	1	0/108 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/113 (0.9%)	1	0/108 (0%)	0
Respiratory Failure	1/113 (0.9%)	1	0/108 (0%)	0
Skin and subcutaneous tissue disorders
Uticaria	1/113 (0.9%)	1	3/108 (2.8%)	3
Panniculitis	1/113 (0.9%)	1	1/108 (0.9%)	1
Psoriasis	0/113 (0%)	0	1/108 (0.9%)	1
Rash	1/113 (0.9%)	1	0/108 (0%)	0
Vascular disorders
Hypertension	1/113 (0.9%)	1	2/108 (1.9%)	2
Other (Not Including Serious) Adverse Events
	1 Atorvastatin		2 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/113 (83.2%)		95/108 (88%)
Blood and lymphatic system disorders
Leukopenia	8/113 (7.1%)	13	6/108 (5.6%)	9
Eye disorders
Conjunctivitis	2/113 (1.8%)	2	6/108 (5.6%)	6
Gastrointestinal disorders
Gastrointestinal Disorder	10/113 (8.8%)	14	8/108 (7.4%)	8
General disorders
Non-Cardiac Chest Pain	6/113 (5.3%)	7	4/108 (3.7%)	4
Fatigue	2/113 (1.8%)	2	6/108 (5.6%)	6
Infections and infestations
Upper Respiratory Tract Infection	15/113 (13.3%)	17	18/108 (16.7%)	24
Sinusitis	11/113 (9.7%)	15	7/108 (6.5%)	11
Urinary Tract Infection	8/113 (7.1%)	11	10/108 (9.3%)	16
Herpes Zoster	4/113 (3.5%)	5	12/108 (11.1%)	12
Bronchitis	6/113 (5.3%)	7	3/108 (2.8%)	3
Investigations
Alanine Aminotransferase Increased	8/113 (7.1%)	10	9/108 (8.3%)	11
Blood Creatine Phosphokinase Increased	8/113 (7.1%)	14	7/108 (6.5%)	11
Aspartate Aminotransferase Increased	6/113 (5.3%)	8	5/108 (4.6%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	10/113 (8.8%)	12	10/108 (9.3%)	15
Systemic Lupus Erythematosus	10/113 (8.8%)	14	8/108 (7.4%)	11
Back Pain	9/113 (8%)	10	5/108 (4.6%)	5
Osteonecrosis	5/113 (4.4%)	9	6/108 (5.6%)	11
Myositis	6/113 (5.3%)	6	3/108 (2.8%)	3
Nervous system disorders
Neurotoxicity	27/113 (23.9%)	62	25/108 (23.1%)	51
Headache	7/113 (6.2%)	9	7/108 (6.5%)	7
Renal and urinary disorders
Proteinuria	12/113 (10.6%)	19	8/108 (7.4%)	11
Respiratory, thoracic and mediastinal disorders
Cough	4/113 (3.5%)	6	8/108 (7.4%)	8
Skin and subcutaneous tissue disorders
Rash	19/113 (16.8%)	28	28/108 (25.9%)	47
Vascular disorders
Hypertension	13/113 (11.5%)	30	12/108 (11.1%)	25

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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