E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV seropositive |
Seropositivo para el HIV |
|
E.1.1.1 | Medical condition in easily understood language |
HIV seropositive |
seropositivo para el VIH |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008919 |
E.1.2 | Term | Chronic HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058315 |
E.1.2 | Term | HIV disease progression |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
Proportion of patients with decreased collagen deposition in TL equal to or greater than 50%. |
Proporción de pacientes con disminución del deposito de colágeno en TL igual o mayor al 50% |
|
E.2.2 | Secondary objectives of the trial |
1. Changes in markers of fibrosis and immune recovery TL: the ratio of MMP-9/TIMP-1 and MMP-2 / TIMP-2 in the TL, Changes in the count of CD4 + T cells in peripheral blood and LT changes the CD4/CD8 ratio in peripheral blood, changes in the value of HIV viral load in peripheral blood and LT.
2. Changes in markers of atherosclerosis: To determine the levels of IL-6, D-dimer and CRP in the different groups and changes in the diameter of the carotid intima as a marker of atherosclerosis.
3. Changes in markers of dementia and CNS inflammation: measuring levels of metalloproteinases and their inhibitors in cerebrospinal fluid, as well as beta2-microglobulin levels and levels of cells and proteins. Changes in neuropsychological test diagnosis of CDS.
4. Adverse Events. |
1. Cambios en los marcadores de fibrosis de TL y de recuperación inmunológica: el cociente MMP-9/TIMP-1 y MMP-2/ TIMP-2 en el TL, Cambios en el recuento de linfocitos T CD4+ en sangre periférica y TL, Cambios en el cociente CD4/CD8 en sangre periférica, Cambios en el valor de la carga vírica del VIH en sangre periférica y TL.
2. Cambios en los marcadores de arteriosclerosis: Determinar los niveles de IL-6, D-dímero y PCR ultrasensible en los diferentes grupo y los cambios en el diámetro de la íntima carotídea como marcador de arteriosclerosis.
3. Cambios en los marcadores de demencia e inflamación de SNC: medición de los niveles de metaloproteasas y sus inhibidores en liquido cefalorraquídeo, además de niveles de beta2-microglobulina y niveles de células y proteinas . Cambios en test neuropsicológicos diagnósticos de CDS.
4. Efectos adversos. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients older than 18 years.
2. Patients with HIV infection in antiretroviral treatment with EFV / FTC / TDF with undetectable viral load (VL <37 copies) for at least 48 weeks.
3. Nadir CD4 +> 250 cells/mm3.
4. Patients, properly informed, give their written consent to participate in the study. |
1. Pacientes con edad superior a 18 años.
2. Pacientes con infección por HIV en tratamiento antiretroviral con EFV/FTC/TDF y con carga viral indetectable (CV < 37 copias) durante al menos 48 semanas.
3. Nadir de CD4+ > 250 cel/mm3 (se permitirá una determinación < 250 cel/mm3 si se trata de una sola determinación aislada)
4. Pacientes que, adecuadamente informados, otorguen su consentimiento por escrito para participar en el estudio y someterse a las pruebas y exploraciones que ello comporta.
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E.4 | Principal exclusion criteria |
1. Criteria for patients with AIDS.
2. Patients with active opportunistic diseases.
3. Patients coinfected with HCV.
4. Patients without tonsillar tissue.
5. Treatment with other drugs receptor antagonists or angiotensin II converting enzyme inhibitors, angiotensin II.
6. Kidney failure.(Glomerular Filtration Rate (GFR < 60 mL/mn)
7. Severe liver failure (PT> 60% ).
8. Pregnant women
9. Known hypersensitivity or contraindication to any study drug.
10. determination of blood pressure (BP) <100/60 mmHg
11. Hyponatremia with serum Na numbers <132 Meq / l
12. History of chronic vomiting the last 6 months
13. History of chronic diarrhea the last 6 months |
1. Pacientes con criterios de SIDA.
2. Pacientes con enfermedades oportunistas activas.
3. Pacientes coinfectados por VHC.
4. Pacientes sin tejido amigdalar.
5. Tratamiento con otros fármacos antagonistas del receptor de la angiotensina II o con inhibidores de la enzima convertidora de la angiotensina II (ANEXO 3)
6. Insuficiencia renal (filtrado glomerular calculado con la fórmula MDRD) < 60 mL/min).
7. Insuficiencia hepática grave (tiempo de protrombina < 60%).
8. Embarazadas
9. Hipersensibilidad conocida o contraindicación a algún fármaco del estudio.
10. Cifras de Tensión arterial (TA) < 100/60 mmHg
11. Hiponatremia con cifras de Na sérico < 132 Meq/l
12. Antecedentes de vómitos de repetición los últimos 6 meses
13. Antecedentes de diarrea crónica los últimos 6 meses.
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|
E.5 End points |
E.5.1 | Primary end point(s) |
Proporción de pacientes con disminución del 50% de fibrosis en TL. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Proporción de pacientes con cambios en los niveles de IL-6, D-dímero y PCR ultrasensible en los diferentes grupos.
- Proporción de pacientes con aumento de CD4 en sangre periférica y en TL en los diferentes grupos.
- Proporción de pacientes con carga viral indetectable en plasma y disminuida en TL en los diferentes grupos
- Proporción de pacientes con cambios en el cociente CD4/CD8 en sangre periférica en los diferentes grupos.
- Proporción de pacientes con disminución del complejo íntima media en la ecografía carotídea en los diferentes grupos.
- Proporción de pacientes con cambios en niveles de metaloproteasas y sus inhibidores , beta2 -microglobulina y células y proteínas en LCR.
- Proporción de pacientes con mejoría de los test neuropsicologicos de CDS
- Incidencia y tipos de efectos adversos clínicos y alteraciones analíticas en los diferentes grupos. |
|
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 | No |
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 | Yes |
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 | 4 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |