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

8 maart 2016 bijgewerkt door: International Maternal Pediatric Adolescent AIDS Clinical Trials Group

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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

28

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Colorado
      • Aurora, Colorado, Verenigde Staten, 80045
        • Univ. of Colorado Denver NICHD CRS (5052)
    • Florida
      • Miami, Florida, Verenigde Staten, 33136
        • Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
      • Tampa, Florida, Verenigde Staten, 33620
        • University of South Florida Tampa (5018)
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60614
        • Chicago Children's CRS (4001)
    • Louisiana
      • New Orleans, Louisiana, Verenigde Staten, 70112
        • Tulane University (5095)
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02118
        • Boston Medical Center Ped. HIV Program NICHD CRS (5011)
    • New York
      • Bronx, New York, Verenigde Staten, 10457
        • Bronx-Lebanon Hospital IMPAACT CRS (6901)
      • New York, New York, Verenigde Staten, 10016
        • New York University NY (5012)
      • New York, New York, Verenigde Staten, 10029
        • Metropolitan Hospital (5003)
    • Tennessee
      • Memphis, Tennessee, Verenigde Staten, 38105
        • St. Jude/UTHSC CRS (6501)
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • Texas Children's Hosp. CRS (3801)

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

10 jaar tot 23 jaar (Kind, Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Age 10 to 14
Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Geneesmiddel: Atorvastatin
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Andere namen:
  • Lipitor
Experimenteel: Age 15 to 23
Participants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Geneesmiddel: Atorvastatin
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Andere namen:
  • Lipitor

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)
Tijdsspanne: Study entry to weeks 12, 24, and 48
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)
Tijdsspanne: Study entry to weeks 12, 24, and 48
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)
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
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)
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
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)
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
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
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
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
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
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
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
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
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
Study entry and weeks 4, 12, 24, and 48
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) by Age Group
Tijdsspanne: Study entry to weeks 12, 24, and 48
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
Tijdsspanne: Study entry to weeks 12, 24, and 48
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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
Study entry and weeks 4, 12, 24, and 48
Percent Change in Triglycerides (TG) From Study Entry
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
Study entry and weeks 4, 12, 24, and 48
Percent Change in HDL-cholesterol (HDL-C) From Study Entry
Tijdsspanne: Study entry and weeks 4, 12, 24, and 48
Study entry and weeks 4, 12, 24, and 48
Percent Change in Apolipoprotein A1 (Apo A-1) From Study Entry
Tijdsspanne: Study entry and weeks 12, 24, and 48
Study entry and weeks 12, 24, and 48
Percent Change in Apolipoprotein B (Apo B) From Study Entry
Tijdsspanne: Study entry and weeks 12, 24, and 48
Study entry and weeks 12, 24, and 48
Percent Change in High-sensitivity CRP (Hs-CRP) From Study Entry
Tijdsspanne: Study entry and weeks 12, 24, and 48
Study entry and weeks 12, 24, and 48
Percent Change in Interleukin 6 (IL-6) From Study Entry
Tijdsspanne: Study entry and weeks 12, 24, and 48
Study entry and weeks 12, 24, and 48
Percentage of Participants With Undetectable Plasma HIV-1 RNA
Tijdsspanne: Study entry and weeks 12, 24, and 48
Undetectable is defined as plasma HIV-1 RNA below the lower limit of quantification of the assay used.
Study entry and weeks 12, 24, and 48

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Medewerkers

National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Onderzoekers

  • Studie stoel: Ann Melvin, MD, Seattle Children's Hospital
  • Studie stoel: Marilyn Crain, MD, MPH, University of Alabama at Birmingham

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 augustus 2009

Primaire voltooiing (Werkelijk)

1 december 2014

Studie voltooiing (Werkelijk)

1 december 2014

Studieregistratiedata

Eerst ingediend

21 april 2008

Eerst ingediend dat voldeed aan de QC-criteria

21 april 2008

Eerst geplaatst (Schatting)

22 april 2008

Updates van studierecords

Laatste update geplaatst (Schatting)

6 april 2016

Laatste update ingediend die voldeed aan QC-criteria

8 maart 2016

Laatst geverifieerd

1 maart 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • IMPAACT P1063
  • U01AI068632 (Subsidie/contract van de Amerikaanse NIH)
  • 10167

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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