IMPAACT P1063: Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia

NCT ID: NCT00663234

Last Updated: 2016-04-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2014-12-31

Brief Summary

Treatment of HIV with combination antiretroviral regimens frequently results in the suppression of HIV viral load, significant immune recovery, and delayed disease progression. However, treatment with these regimens, particularly protease inhibitors (PIs), has been associated with significant increases in cholesterol and triglycerides in HIV-infected adults and children. The purpose of this study was to evaluate the safety and effectiveness of escalating doses of atorvastatin, a FDA-approved drug which lowers cholesterol and triglyceride levels, in HIV-infected children receiving stable antiretroviral regimens.

Detailed Description

Antiretroviral regimens, particularly those containing PIs, often cause hyperlipidemia, which is an increase in the amount of fat (such as cholesterol and triglycerides) in the blood. These increases can lead to heart disease and pancreatitis. Although the mechanism by which PIs cause hyperlipidemia is not clearly understood, there are medications to combat this side effect. The primary purpose of this study was to evaluate the safety and effectiveness of escalating doses of atorvastatin, based on low-density lipoprotein cholesterol (LDL-C) levels, in HIV-infected children receiving stable antiretroviral therapy.

Participants were assigned to one of two groups based on age (10 to 14 years or 15 to 23 years) and were treated for a maximum of 48 weeks. The first six participants enrolled in the study were in the 15 to 23 year old age group. Once safety data through week 8 on these 6 participants was analyzed, the remaining participants were enrolled. All participants received atorvastatin in combination with a stable antiretroviral regimen. Each participant was followed independently according to a dose escalation algorithm for atorvastatin. Participants began dosing at 10 mg daily. If efficacy criteria were not met, dosing increased to 20 mg daily at week 8. Since dose escalations were done within subject, safety and efficacy rates were presented for the dose-escalation strategy overall and not for individual doses. Atorvastatin was provided by the study, but antiretrovirals were not.

Study visits occurred at study entry and weeks 4, 8, 12, 24, 36, and 48. Safety labs were collected at all study visits. Blood collection for lipid measurements occurred at weeks 4, 12, 24 and 48.

Conditions

HIV Infections; Hyperlipidemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Age 10 to 14

Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.

Age 15 to 23

Participants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.

Interventions

Atorvastatin

10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.

Intervention Type: DRUG

Other Intervention Names

Lipitor

Eligibility Criteria

Inclusion Criteria

• A diagnosis of HIV-1 infection
• CD4 % of at least 15 at screening
• HIV-1 viral load of less than 10,000 copies/ml at screening
• On a stable antiretroviral therapy regimen for at least 6 months
• Tanner stage of 2 or higher
• At least two LDL-C measurements of 130 mg/dL or higher over the 6 months prior to screening and after documented attempts at modifying diet and other risk factors. More information on this criterion can be found in the protocol.
• Able to fast overnight for 8 hours
• Negative pregnancy test at screening
• Agree to use two appropriate forms of contraception (female participants). More information on this criterion can be found in the protocol.

Exclusion Criteria

• Certain abnormal laboratory values
• Any laboratory or unresolved clinical toxicity of Grade 3 or higher
• Unlikely to remain on current antiretroviral therapy for at least six months after study entry
• Use of statin, fibrate, or niacin within 3 months prior to study entry
• Evidence of chronic ongoing myositis or history of myopathy or neuromuscular disorder
• Symptomatic peripheral neuropathy within 6 months prior to study entry
• Pharmacologic treatment for depression or other mental disorder excluding Attention Deficit Disorder within 30 days prior to study entry
• Presence of an active CDC Stage C opportunistic infection or serious bacterial infection requiring therapy within 2 weeks prior to screening.
• Chemotherapy for malignancy within 3 months prior to study entry
• Hepatitis B Surface Antigen positive
• Hepatitis C viremia
• Insulin-dependent diabetes mellitus
• Required treatment with an agent contraindicated with either atorvastatin or PIs. More information on this criterion can be found in the protocol.
• Pregnant or breastfeeding

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 23 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann Melvin, MD

Role: STUDY_CHAIR

Seattle Children's Hospital

Marilyn Crain, MD, MPH

Role: STUDY_CHAIR

University of Alabama at Birmingham

Locations

Univ. of Colorado Denver NICHD CRS (5052)

Aurora, Colorado, United States

Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)

Miami, Florida, United States

University of South Florida Tampa (5018)

Tampa, Florida, United States

Chicago Children's CRS (4001)

Chicago, Illinois, United States

Tulane University (5095)

New Orleans, Louisiana, United States

Boston Medical Center Ped. HIV Program NICHD CRS (5011)

Boston, Massachusetts, United States

New York University NY (5012)

New York, New York, United States

Metropolitan Hospital (5003)

New York, New York, United States

Bronx-Lebanon Hospital IMPAACT CRS (6901)

The Bronx, New York, United States

St. Jude/UTHSC CRS (6501)

Memphis, Tennessee, United States

Texas Children's Hosp. CRS (3801)

Houston, Texas, United States

Countries

United States

References

Kamin D, Hadigan C. Hyperlipidemia in children with HIV infection: an emerging problem. Expert Rev Cardiovasc Ther. 2003 May;1(1):143-50. doi: 10.1586/14779072.1.1.143.

Reference Type: BACKGROUND

PMID: 15030304 (View on PubMed)

Penzak SR, Chuck SK. Management of protease inhibitor-associated hyperlipidemia. Am J Cardiovasc Drugs. 2002;2(2):91-106. doi: 10.2165/00129784-200202020-00003.

Reference Type: BACKGROUND

PMID: 14727985 (View on PubMed)

Solorzano Santos F, Gochicoa Rangel LG, Palacios Saucedo G, Vazquez Rosales G, Miranda Novales MG. Hypertriglyceridemia and hypercholesterolemia in human immunodeficiency virus-1-infected children treated with protease inhibitors. Arch Med Res. 2006 Jan;37(1):129-32. doi: 10.1016/j.arcmed.2005.05.013.

Reference Type: BACKGROUND

PMID: 16314198 (View on PubMed)

The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)

Reference Type: BACKGROUND

Other Identifiers

U01AI068632

Identifier Type: NIH

Identifier Source: secondary_id

View Link

10167

Identifier Type: -

Identifier Source: secondary_id

IMPAACT P1063

Identifier Type: -

Identifier Source: org_study_id