- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica 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
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
-
-
Colorado
-
Aurora, Colorado, Stati Uniti, 80045
- Univ. of Colorado Denver NICHD CRS (5052)
-
-
Florida
-
Miami, Florida, Stati Uniti, 33136
- Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
-
Tampa, Florida, Stati Uniti, 33620
- University of South Florida Tampa (5018)
-
-
Illinois
-
Chicago, Illinois, Stati Uniti, 60614
- Chicago Children's CRS (4001)
-
-
Louisiana
-
New Orleans, Louisiana, Stati Uniti, 70112
- Tulane University (5095)
-
-
Massachusetts
-
Boston, Massachusetts, Stati Uniti, 02118
- Boston Medical Center Ped. HIV Program NICHD CRS (5011)
-
-
New York
-
Bronx, New York, Stati Uniti, 10457
- Bronx-Lebanon Hospital IMPAACT CRS (6901)
-
New York, New York, Stati Uniti, 10016
- New York University NY (5012)
-
New York, New York, Stati Uniti, 10029
- Metropolitan Hospital (5003)
-
-
Tennessee
-
Memphis, Tennessee, Stati Uniti, 38105
- St. Jude/UTHSC CRS (6501)
-
-
Texas
-
Houston, Texas, Stati Uniti, 77030
- Texas Children's Hosp. CRS (3801)
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Age 10 to 14
Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
|
10 mg to 20 mg atorvastatin taken orally once daily.
Dosage is dependent on efficacy criteria.
Altri nomi:
|
Sperimentale: Age 15 to 23
Participants ages 15 to 23 years receiving oral atorvastatin for 48 weeks while on a stable antiretroviral regimen
|
10 mg to 20 mg atorvastatin taken orally once daily.
Dosage is dependent on efficacy criteria.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Percentage of Participants Experiencing at Least One Treatment-related Adverse Event (AE)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Percent Change in Fasting Total Cholesterol (TC) From Study Entry
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Collaboratori
Investigatori
- Cattedra di studio: Ann Melvin, MD, Seattle Children's Hospital
- Cattedra di studio: Marilyn Crain, MD, MPH, University of Alabama at Birmingham
Pubblicazioni e link utili
Pubblicazioni generali
- 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)
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie metaboliche
- Disturbi del metabolismo lipidico
- Dislipidemie
- Iperlipidemie
- Iperlipoproteinemie
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Antimetaboliti
- Agenti anticolesteremici
- Agenti ipolipidemizzanti
- Agenti regolatori dei lipidi
- Inibitori dell'idrossimetilglutaril-CoA reduttasi
- Atorvastatina
Altri numeri di identificazione dello studio
- IMPAACT P1063
- U01AI068632 (Sovvenzione/contratto NIH degli Stati Uniti)
- 10167
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Infezioni da HIV
-
University of MinnesotaRitiratoInfezioni da HIV | HIV/AIDS | HIV | AIDS | Problema di Aids/Hiv | AIDS e infezioniStati Uniti
-
Erasmus Medical CenterNon ancora reclutamentoInfezioni da HIV | HIV | Infezione da HIV-1 | Infezione da HIV IOlanda
-
Helios SaludViiV HealthcareSconosciutoHIV | Infezione da HIV-1Argentina
-
ANRS, Emerging Infectious DiseasesHopital Universitaire Robert-Debre; Institut de Recherche pour le Developpement; Centre Pasteur du Cameroun e altri collaboratoriSconosciutoHIV | Bambini non infetti da HIV | Bambini esposti all'HIVCamerun
-
University of MinnesotaCompletatoInfezioni da HIV | HIV | ImmunodeficienzaStati Uniti
-
Allegheny Singer Research Institute (also known...Attivo, non reclutanteInfezioni da HIV | Infezione da HIV-1 | Infezione da HIV IStati Uniti
-
University of California, DavisCompletato
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completato
-
University of ZimbabweCompletato
-
Boston Children's HospitalNational Institute on Minority Health and Health Disparities (NIMHD)Completato
Prove cliniche su Atorvastatin
-
Peking Union Medical College HospitalReclutamentoFemmina di cancro al senoCina
-
Dong-A ST Co., Ltd.Sconosciuto
-
University Hospital Inselspital, BernePharmaPart; Viollier AG, Basel, SwitzerlandCompletatoSclerosi multipla recidivante-remittenteSvizzera
-
Zhejiang Hisun Pharmaceutical Co. Ltd.Sconosciuto
-
CHU de Quebec-Universite LavalCanadian Institutes of Health Research (CIHR); BiovaloremReclutamentoTumore del pancreas | Cancro metastatico | Adenocarcinoma duttale pancreatico | Cancro al pancreasCanada