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

NCT00663234 | Terminated Phase 1 Results DMC

• 3 other identifiers: IMPAACT P1063U01AI06863210167
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 11

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.

Conditions

HIV Infections; Hyperlipidemia

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (11)

• Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)

  AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the core study team. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

  Study entry to weeks 12, 24, and 48

• Percentage of Participants Experiencing at Least One Adverse Event (AE)

  AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

  Study entry to weeks 12, 24, and 48

• Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Intention to Treat)

  Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.

  Study entry and weeks 4, 12, 24, and 48

• Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Data Available)

  Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.

  Study entry and weeks 4, 12, 24, and 48

• Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Per Protocol)

  Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.

  Study entry and weeks 4, 12, 24, and 48

• Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria and Did Not Experience a Primary Safety Endpoint Attributable to Study Drug

  Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.

  Study entry and weeks 4, 12, 24, and 48

• Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by Age Group

  Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.

  Study entry and weeks 4, 12, 24, and 48

• Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by NNRTI Treatment

  Efficacy was defined as having LDL-C of 110 mg/dL or less or at least 30% decline in LDL-C from baseline to the specified week.

  Study entry and weeks 4, 12, 24, and 48

• Percent Change in LDL Cholesterol (LDL-C) From Study Entry

  Study entry and weeks 4, 12, 24, and 48

• Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) by Age Group

  AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the core study team. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

  Study entry to weeks 12, 24, and 48

• Percentage of Participants Experiencing at Least One Adverse Event (AE) by Age Group

  AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. The primary outcome measure includes any AE of grade 3 or higher and liver function tests (LFTs) of grade 2 or higher.

  Study entry to weeks 12, 24, and 48

Secondary Outcomes (8)

• Percent Change in Fasting Total Cholesterol (TC) From Study Entry

  Study entry and weeks 4, 12, 24, and 48

• Percent Change in Triglycerides (TG) From Study Entry

  Study entry and weeks 4, 12, 24, and 48

• Percent Change in HDL-cholesterol (HDL-C) From Study Entry

  Study entry and weeks 4, 12, 24, and 48

• Percent Change in Apolipoprotein A1 (Apo A-1) From Study Entry

  Study entry and weeks 12, 24, and 48

• Percent Change in Apolipoprotein B (Apo B) From Study Entry

  Study entry and weeks 12, 24, and 48

Study Arms (2)

Age 10 to 14

EXPERIMENTAL

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

Drug: Atorvastatin

Age 15 to 23

EXPERIMENTAL

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

Drug: Atorvastatin

Interventions

Atorvastatin DRUG

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

Also known as: Lipitor

Age 10 to 14; Age 15 to 23

Eligibility Criteria

• Age: 10 Years - 23 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (11)

Univ. of Colorado Denver NICHD CRS (5052)

Aurora, Colorado, 80045, United States

Location

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

Miami, Florida, 33136, United States

Location

University of South Florida Tampa (5018)

Tampa, Florida, 33620, United States

Location

Chicago Children's CRS (4001)

Chicago, Illinois, 60614, United States

Location

Tulane University (5095)

New Orleans, Louisiana, 70112, United States

Location

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

Boston, Massachusetts, 02118, United States

Location

New York University NY (5012)

New York, New York, 10016, United States

Location

Metropolitan Hospital (5003)

New York, New York, 10029, United States

Location

Bronx-Lebanon Hospital IMPAACT CRS (6901)

The Bronx, New York, 10457, United States

Location

St. Jude/UTHSC CRS (6501)

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hosp. CRS (3801)

Houston, Texas, 77030, United States

Location

Related Publications (4)

• 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.

  PMID: 15030304 BACKGROUND

• 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.

  PMID: 14727985 BACKGROUND

• 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.

  PMID: 16314198 BACKGROUND

• 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)

  BACKGROUND

MeSH Terms

Conditions

HIV Infections; Hyperlipidemias

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

Target enrollment was 40 participants (20 in each age cohort). However, the study was prematurely discontinued due to administrative reasons, having enrolled only 28 participants (21 participants aged 10 to 14 and 7 participants aged 15 to 23).

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Ann Melvin, MD

  Seattle Children's Hospital

  STUDY CHAIR

• Marilyn Crain, MD, MPH

  University of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2008
• First Posted: April 22, 2008
• Study Start: August 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 6, 2016
• Results First Posted: April 6, 2016

Record last verified: 2016-03

Locations

US (11)