- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00663234
IMPAACT P1063: Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia
Phase I/II Safety and Efficacy Investigation of Atorvastatin for Treatment of PI-Associated Increased LDL Cholesterol in HIV-Infected Children and Adolescents
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
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Colorado
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Aurora, Colorado, Vereinigte Staaten, 80045
- Univ. of Colorado Denver NICHD CRS (5052)
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Florida
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Miami, Florida, Vereinigte Staaten, 33136
- Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
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Tampa, Florida, Vereinigte Staaten, 33620
- University of South Florida Tampa (5018)
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Illinois
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Chicago, Illinois, Vereinigte Staaten, 60614
- Chicago Children's CRS (4001)
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Louisiana
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New Orleans, Louisiana, Vereinigte Staaten, 70112
- Tulane University (5095)
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Massachusetts
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Boston, Massachusetts, Vereinigte Staaten, 02118
- Boston Medical Center Ped. HIV Program NICHD CRS (5011)
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New York
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Bronx, New York, Vereinigte Staaten, 10457
- Bronx-Lebanon Hospital IMPAACT CRS (6901)
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New York, New York, Vereinigte Staaten, 10016
- New York University NY (5012)
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New York, New York, Vereinigte Staaten, 10029
- Metropolitan Hospital (5003)
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Tennessee
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Memphis, Tennessee, Vereinigte Staaten, 38105
- St. Jude/UTHSC CRS (6501)
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Texas
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Houston, Texas, Vereinigte Staaten, 77030
- Texas Children's Hosp. CRS (3801)
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Age 10 to 14
Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
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10 mg to 20 mg atorvastatin taken orally once daily.
Dosage is dependent on efficacy criteria.
Andere Namen:
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Experimental: Age 15 to 23
Participants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
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10 mg to 20 mg atorvastatin taken orally once daily.
Dosage is dependent on efficacy criteria.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)
Zeitfenster: Study entry to weeks 12, 24, and 48
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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.
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Study entry to weeks 12, 24, and 48
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Percentage of Participants Experiencing at Least One Adverse Event (AE)
Zeitfenster: Study entry to weeks 12, 24, and 48
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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.
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Study entry to weeks 12, 24, and 48
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Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Intention to Treat)
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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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.
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Study entry and weeks 4, 12, 24, and 48
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Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Data Available)
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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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.
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Study entry and weeks 4, 12, 24, and 48
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Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria (Per Protocol)
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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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.
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Study entry and weeks 4, 12, 24, and 48
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Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria and Did Not Experience a Primary Safety Endpoint Attributable to Study Drug
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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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.
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Study entry and weeks 4, 12, 24, and 48
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Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by Age Group
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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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.
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Study entry and weeks 4, 12, 24, and 48
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Percentage of Participants Who Met the LDL Cholesterol (LDL-C) Efficacy Criteria by NNRTI Treatment
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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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.
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Study entry and weeks 4, 12, 24, and 48
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Percent Change in LDL Cholesterol (LDL-C) From Study Entry
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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Study entry and weeks 4, 12, 24, and 48
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Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE) by Age Group
Zeitfenster: Study entry to weeks 12, 24, and 48
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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
Zeitfenster: 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.
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Study entry to weeks 12, 24, and 48
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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Study entry and weeks 4, 12, 24, and 48
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Percent Change in Triglycerides (TG) From Study Entry
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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Study entry and weeks 4, 12, 24, and 48
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Percent Change in HDL-cholesterol (HDL-C) From Study Entry
Zeitfenster: Study entry and weeks 4, 12, 24, and 48
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Study entry and weeks 4, 12, 24, and 48
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Percent Change in Apolipoprotein A1 (Apo A-1) From Study Entry
Zeitfenster: Study entry and weeks 12, 24, and 48
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Study entry and weeks 12, 24, and 48
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Percent Change in Apolipoprotein B (Apo B) From Study Entry
Zeitfenster: Study entry and weeks 12, 24, and 48
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Study entry and weeks 12, 24, and 48
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Percent Change in High-sensitivity CRP (Hs-CRP) From Study Entry
Zeitfenster: Study entry and weeks 12, 24, and 48
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Study entry and weeks 12, 24, and 48
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Percent Change in Interleukin 6 (IL-6) From Study Entry
Zeitfenster: Study entry and weeks 12, 24, and 48
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Study entry and weeks 12, 24, and 48
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Percentage of Participants With Undetectable Plasma HIV-1 RNA
Zeitfenster: Study entry and weeks 12, 24, and 48
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Undetectable is defined as plasma HIV-1 RNA below the lower limit of quantification of the assay used.
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Study entry and weeks 12, 24, and 48
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Mitarbeiter und Ermittler
Mitarbeiter
Ermittler
- Studienstuhl: Ann Melvin, MD, Seattle Children's Hospital
- Studienstuhl: Marilyn Crain, MD, MPH, University of Alabama at Birmingham
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
- 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.
- 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.
- 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)
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Stoffwechselerkrankungen
- Störungen des Fettstoffwechsels
- Dyslipidämien
- Hyperlipidämien
- Hyperlipoproteinämien
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antimetaboliten
- Anticholesterämische Mittel
- Hypolipidämische Mittel
- Lipidregulierende Mittel
- Hydroxymethylglutaryl-CoA-Reduktase-Inhibitoren
- Atorvastatin
Andere Studien-ID-Nummern
- IMPAACT P1063
- U01AI068632 (US NIH Stipendium/Vertrag)
- 10167
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