search
Back to results

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

Primary Purpose

HIV Infections, Hyperlipidemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atorvastatin
Sponsored by
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Treatment Experienced

Eligibility Criteria

10 Years - 23 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Univ. of Colorado Denver NICHD CRS (5052)
  • Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
  • University of South Florida Tampa (5018)
  • Chicago Children's CRS (4001)
  • Tulane University (5095)
  • Boston Medical Center Ped. HIV Program NICHD CRS (5011)
  • Bronx-Lebanon Hospital IMPAACT CRS (6901)
  • New York University NY (5012)
  • Metropolitan Hospital (5003)
  • St. Jude/UTHSC CRS (6501)
  • Texas Children's Hosp. CRS (3801)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Age 10 to 14

Age 15 to 23

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Percent Change in Triglycerides (TG) From Study Entry
Percent Change in HDL-cholesterol (HDL-C) From Study Entry
Percent Change in Apolipoprotein A1 (Apo A-1) From Study Entry
Percent Change in Apolipoprotein B (Apo B) From Study Entry
Percent Change in High-sensitivity CRP (Hs-CRP) From Study Entry
Percent Change in Interleukin 6 (IL-6) From Study Entry
Percentage of Participants With Undetectable Plasma HIV-1 RNA
Undetectable is defined as plasma HIV-1 RNA below the lower limit of quantification of the assay used.

Full Information

First Posted
April 21, 2008
Last Updated
March 8, 2016
Sponsor
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
search

1. Study Identification

Unique Protocol Identification Number
NCT00663234
Brief Title
IMPAACT P1063: Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia
Official Title
Phase I/II Safety and Efficacy Investigation of Atorvastatin for Treatment of PI-Associated Increased LDL Cholesterol in HIV-Infected Children and Adolescents
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
The study was prematurely discontinued due to administrative reasons.
Study Start Date
August 2009 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Hyperlipidemia
Keywords
Treatment Experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Age 10 to 14
Arm Type
Experimental
Arm Description
Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Arm Title
Age 15 to 23
Arm Type
Experimental
Arm Description
Participants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Other Intervention Name(s)
Lipitor
Intervention Description
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)
Description
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.
Time Frame
Study entry to weeks 12, 24, and 48
Title
Percentage of Participants Experiencing at Least One Adverse Event (AE)
Description
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.
Time Frame
Study entry to weeks 12, 24, and 48
Title
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Intention to Treat)
Description
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.
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Data Available)
Description
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.
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Per Protocol)
Description
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.
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria and Did Not Experience a Primary Safety Endpoint Attributable to Study Drug
Description
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.
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by Age Group
Description
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.
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by NNRTI Treatment
Description
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.
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percent Change in LDL Cholesterol (LDL-C) From Study Entry
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) by Age Group
Description
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.
Time Frame
Study entry to weeks 12, 24, and 48
Title
Percentage of Participants Experiencing at Least One Adverse Event (AE) by Age Group
Description
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.
Time Frame
Study entry to weeks 12, 24, and 48
Secondary Outcome Measure Information:
Title
Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percent Change in Triglycerides (TG) From Study Entry
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percent Change in HDL-cholesterol (HDL-C) From Study Entry
Time Frame
Study entry and weeks 4, 12, 24, and 48
Title
Percent Change in Apolipoprotein A1 (Apo A-1) From Study Entry
Time Frame
Study entry and weeks 12, 24, and 48
Title
Percent Change in Apolipoprotein B (Apo B) From Study Entry
Time Frame
Study entry and weeks 12, 24, and 48
Title
Percent Change in High-sensitivity CRP (Hs-CRP) From Study Entry
Time Frame
Study entry and weeks 12, 24, and 48
Title
Percent Change in Interleukin 6 (IL-6) From Study Entry
Time Frame
Study entry and weeks 12, 24, and 48
Title
Percentage of Participants With Undetectable Plasma HIV-1 RNA
Description
Undetectable is defined as plasma HIV-1 RNA below the lower limit of quantification of the assay used.
Time Frame
Study entry and weeks 12, 24, and 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
23 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Melvin, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Marilyn Crain, MD, MPH
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Study Chair
Facility Information:
Facility Name
Univ. of Colorado Denver NICHD CRS (5052)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of South Florida Tampa (5018)
City
Tampa
State/Province
Florida
ZIP/Postal Code
33620
Country
United States
Facility Name
Chicago Children's CRS (4001)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Tulane University (5095)
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Boston Medical Center Ped. HIV Program NICHD CRS (5011)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Bronx-Lebanon Hospital IMPAACT CRS (6901)
City
Bronx
State/Province
New York
ZIP/Postal Code
10457
Country
United States
Facility Name
New York University NY (5012)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Metropolitan Hospital (5003)
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
St. Jude/UTHSC CRS (6501)
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Texas Children's Hosp. CRS (3801)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15030304
Citation
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.
Results Reference
background
PubMed Identifier
14727985
Citation
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.
Results Reference
background
PubMed Identifier
16314198
Citation
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.
Results Reference
background
Citation
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)
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs