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HIV InfectionsPhase 1/2NCT00663234

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

A Phase 1/2 study testing Atorvastatin in people with HIV Infections and Hyperlipidemia, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 11 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 10 to 23 years
Conditions the study is for
HIV Infections, Hyperlipidemia
What is being tested?
Atorvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
11 sitesUnited States
Study dates
Aug 2009to Dec 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 23 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites
  • Univ. of Colorado Denver NICHD CRS (5052)

    Aurora, Colorado, 80045

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

    Boston, Massachusetts, 02118

  • Chicago Children's CRS (4001)

    Chicago, Illinois, 60614

  • Texas Children's Hosp. CRS (3801)

    Houston, Texas, 77030

  • St. Jude/UTHSC CRS (6501)

    Memphis, Tennessee, 38105

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

    Miami, Florida, 33136

  • Tulane University (5095)

    New Orleans, Louisiana, 70112

  • New York University NY (5012)

    New York, New York, 10016

  • Metropolitan Hospital (5003)

    New York, New York, 10029

  • University of South Florida Tampa (5018)

    Tampa, Florida, 33620

  • Bronx-Lebanon Hospital IMPAACT CRS (6901)

    The Bronx, New York, 10457

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Atorvastatin
Keywords
Treatment Experienced
Medical subject headings
HIV Infections, Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtorvastatinDrug

    Also called Lipitor

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

Study groups in NCT00663234
Study groupRoleWhat they receive
Age 10 to 14ExperimentalParticipants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Receives: Drug: Atorvastatin
Age 15 to 23ExperimentalParticipants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Receives: Drug: Atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Study entry to weeks 12, 24, and 48

  2. 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.

    Measured: Study entry to weeks 12, 24, and 48

  3. 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.

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

  4. 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.

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

  5. 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.

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

  6. 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.

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

  7. 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.

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

  8. 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.

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

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

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

  10. 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.

    Measured: Study entry to weeks 12, 24, and 48

  11. 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.

    Measured: Study entry to weeks 12, 24, and 48

Secondary outcomes (8)
  1. Percent Change in Fasting Total Cholesterol (TC) From Study Entry

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

  2. Percent Change in Triglycerides (TG) From Study Entry

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

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

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

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

    Measured: Study entry and weeks 12, 24, and 48

  5. Percent Change in Apolipoprotein B (Apo B) From Study Entry

    Measured: Study entry and weeks 12, 24, and 48

  6. Percent Change in High-sensitivity CRP (Hs-CRP) From Study Entry

    Measured: Study entry and weeks 12, 24, and 48

  7. Percent Change in Interleukin 6 (IL-6) From Study Entry

    Measured: Study entry and weeks 12, 24, and 48

  8. 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.

    Measured: Study entry and weeks 12, 24, and 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2008 (estimated)
  2. Study startAug 2009
  3. Primary completionDec 2014
  4. Study completionDec 2014

Why it stopped: The study was prematurely discontinued due to administrative reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00663234
Sponsor's protocol ID
IMPAACT P1063
Other IDs
U01AI068632, 10167
Status last verified
Mar 2016
First submitted
21 Apr 2008
Last updated
6 Apr 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 15030304
  • 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.

    PubMed 14727985
  • 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.

    PubMed 16314198
  • 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)

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atorvastatin in people with HIV Infections and Hyperlipidemia, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) (time frame: Study entry to weeks 12, 24, and 48). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00663234, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2016.

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