E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV AND HYPERCHOLESTEROLAEMIA |
VIH E HIPERCOLESTEROLEMIA |
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E.1.1.1 | Medical condition in easily understood language |
HIV and high cholesterol levels |
VIH y altos niveles de colesterol |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect of rosuvastatin to protease inhibitor switching on fasting total cholesterol over 12 weeks |
Comparar el efecto de rosuvastatina o la sustitución de inhibidor de proteasa en el colesterol total en ayunas durante 12 semanas |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of rosuvastatin to protease inhibitor switching on: 1.Total cholesterol through week 12 2.Safety parameters (HIV viral load, clinical adverse events, serious adverse events, laboratory adverse events, modifications to antiretroviral therapy) 3.Quality of life (SF-12) 4.Fasting LDL cholesterol (estimated with Friedwald equation unless triglycerides >400mg/dL, in which case LDL-C would be measured directly), HDL cholesterol, total : HDL cholesterol ratio, LDL particles sizes, triglycerides 5.Fasting glucose and insulin 6.Framingham cardiovascular risk score 7.D:A:D 5-year estimated risk calculator |
Comparar los efectos de rosuvastatina o sustitución de inhibidor de la proteasa sobre:
? Colesterol total en la semana 12 ? Parámetros de seguridad (carga viral, acontecimientos adversos clínicos y de laboratorio, acontecimientos adversos graves, cambios del tratamiento antirretroviral) ? Calidad de vida (cuestionario SF-12) ? Colesterol LDL en ayunas, colesterol HDL, ratio colesterol total/colesterol HDL, tamaño partículas LDL, triglicéridos) ? Glucosa e insulina en ayunas ? Cálculo del riesgo cardiovascular según Framingham ? Cálculo del riesgo cardiovascular según D.A.A. estimado a 5 años |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.HIV-positive status 2.Adults (?18 years of age) 3.Stable and well-tolerated combination ART including a ritonavir-boosted PI for the previous 6 months 4.HIV RNA <50 copies/mL for at least the preceding 3 months 5.Fasting total cholesterol ?5.5 mmol/L (>213 mg/dL) 6.Framingham risk score ?8% at 10 years OR diabetes mellitus OR a family history of premature coronary artery disease in a first-degree relative 7.Provision of written, informed consent |
1. VIH positivos 2. Adultos (?18 años) 3. En combinación estable y bien tolerada de tratamiento antirretroviral que incluya un inhibidor de la proteasa potenciado con ritonavir dutante los últimos 6 meses 4. VIH RNA <50 copies/mL en los últimos 3 meses. 5. Colesterol total en ayunas ?5.5 mmol/L (>213 mg/dL) 6. Fragmingham score ?8% a 10 años o Diabetes mellitus o historia familiar de enfermedad coronaria prematura en familiar de primer grado 7. Otorgar consentimiento informado por escrito |
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E.4 | Principal exclusion criteria |
1.Any statin in the previous 12 weeks 2.Previous statin-induced myopathy or hepatitis 3.History of coronary artery disease, stroke or any other indication for the use of statin therapy (hyperlipidaemia: genetic, secondary or idiopathic) 4.Concurrent use of: ?oral corticosteroids use other than for replacement therapy (ie. prednisolone 5-7.5 mg, hydrocortisone 20-30 mg, cortisone acetate 25-37.5 mg daily) ?other immunosuppressive or immunomodulating drugs 5.Contra-indication to rosuvastatin therapy: ?liver transaminases >5 times the upper normal limit ?creatinine clearance <30 mL/min ?known myopathy ?current fibrate therapy ?known resistance to one or more ?backbone? ART drugs 6.No potent switch ART drug available to replace the current ritonavir-boosted PI 7.Known intolerance to rosuvastatin or the proposed switch ART drug 8.Women attempting or likely to become pregnant, or who are pregnant or breast-feeding 9.A patient with a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study, or interfere with the patient?s participation for the full duration of the study 10.Unable to complete study procedures |
1. Uso de estatinas en las últimas 12 semanas 2. Antecedentes de miopatía o hepatitis inducida por estatinas 3. Antecedentes de enfermedad coronaria, accidente cerebro-vascular, o otras indicaciones para el uso de estatinas (hiperlipidemia: genética, secundaria, o idiopática) 4. Uso concomitante de: - Corticosteroides, salvo tratamiento sustitutivo (p.ej prednisolona 5-7.5 mg, hidrocortisona 20-30 mg, acetato de cortisona 25-37.5 mg /día) - Otros inmunosupresores e inmunomoduladores 5. Contraindicación para el uso de Rosuvastatina: - Transaminasas >5 veces el límite superior de normalidad - Aclaramiento de creatinina < 30mL/min - Miopatía conocida - Uso actual de fibratos - Resistencia a uno o más de los fármacos antirretrovirales que forman parte de la combinación actual 6. Ausencia de antirretroviral para sustituir al actual inhibidor de la proteasa potenciado 7. Intolerancia a Rosuvastatina o a antirretroviral sustitutivo 8. Embarazo o lactancia 9. Cualquier enfermedad médica preexistente conocida que pudiera interferir en la participación del paciente en el ensayo y en su finalización 10. Incapacidad para cumplir con los procedimientos del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change from baseline in total cholesterol at 12 weeks |
Pocentaje medio de cambio de los niveles de colesterol a las 12 semanas respecto la basal |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
? Total cholesterol through week 12 ? Safety parameters (HIV viral load, clinical adverse events, serious adverse events, laboratory adverse events, modifications to antiretroviral therapy) ? Quality of life (SF-12) ? Fasting LDL cholesterol (estimated with Friedwald equation unless triglycerides >400mg/dL, in which case LDL-C would be measured directly), HDL cholesterol, total : HDL cholesterol ratio, LDL particles sizes, triglycerides ? Fasting glucose and insulin ? Framingham cardiovascular risk score (available at: http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof) ? D:A:D 5-year estimated risk calculator (available at: http://www.cphiv.dk/TOOLS/DADRiskEquations/tabid/437/Default.aspx) |
? Colesterol total en la semana 12 ? Parámetros de seguridad (carga viral, acontecimientos adversos clínicos y de laboratorio, acontecimientos adversos graves, cambios del tratamiento antirretroviral) ? Calidad de vida (cuestionario SF-12) ? Colesterol LDL en ayunas, colesterol HDL, ratio colesterol total/colesterol HDL, tamaño partículas LDL, triglicéridos) ? Glucosa e insulina en ayunas ? Cálculo del riesgo cardiovascular según Framingham ? Cálculo del riesgo cardiovascular según D.A.A. estimado a 5 años |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The last visit of the last subject undergoing the trial. |
Se considerará final del ensayo el momento de la última visita del último sujeto reclutado. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |