Tato stránka byla automaticky přeložena a přesnost překladu není zaručena. Podívejte se prosím na anglická verze pro zdrojový text.

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

8. března 2016 aktualizováno: 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.

Přehled studie

Postavení

Ukončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

28

Fáze

  • Fáze 2
  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

10 let až 23 let (Dítě, Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Nerandomizované
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Age 10 to 14
Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Lék: Atorvastatin
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Ostatní jména:
  • Lipitor
Experimentální: Age 15 to 23
Participants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
Lék: Atorvastatin
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Ostatní jména:
  • Lipitor

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Spolupracovníci

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

Vyšetřovatelé

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

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. srpna 2009

Primární dokončení (Aktuální)

1. prosince 2014

Dokončení studie (Aktuální)

1. prosince 2014

Termíny zápisu do studia

První předloženo

21. dubna 2008

První předloženo, které splnilo kritéria kontroly kvality

21. dubna 2008

První zveřejněno (Odhad)

22. dubna 2008

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

6. dubna 2016

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

8. března 2016

Naposledy ověřeno

1. března 2016

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • IMPAACT P1063
  • U01AI068632 (Grant/smlouva NIH USA)
  • 10167

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Klinické studie na HIV infekce

Prohledejte podobné pokusy

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

CROs by country

CROs in Zambia

Podmínky

Vzácné nemoci

Drogové intervence

Doplňky stravy

Sponzor / Spolupracovníci

Místa

3
Předplatit