E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 drug conservation (DC group) strategy with the viral suppression (VS group) strategy in delaying clinical disease progression or death. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the DC group with the VS group for the following: - Survival, Incidence of major cardiovascular and metabolic complications, Incidence of serious disease progression events, Combined endpoint of clinical disease progression, major cardiovascular and metabolic complications, or death, Grade 4 adverse events, Self-reported changes in body appearance, Adherence to antiretroviral treatment, averaged over follow-up, Disease progression, death, and other outcomes above within subgroups. 2.In subsamples of patients, to compare the DC and VS groups for other major disease outcome, Quality of life, HIV transmission risk behaviors, Health care utilization and costs 3. To conduct nested case-control studies in subsamples of patients on predictors of survival and clinical disease progression. 4. To study predictors of survival, disease progression, and major cardiovascular and metabolic complications. 5. Inaddition other protocol defined analyses will be conducted. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Signed informed consent 2. Evidence of HIV infection (positive ELISA and Western Blot and/or documented history of measurable HIV RNA) 3. Age > 13 years (in effect 18 years at most sites) 4. Current CD4+ cell count > 350 cells/mm3 (within 45 days prior to randomization) 5. Willing to initiate, modify, or stop antiretroviral therapy, in accordance with the randomized assignment 6. If participating in sexual activity that could lead to pregnancy, willingness to use acceptable contraception methods |
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E.4 | Principal exclusion criteria |
1. Current participation in the CPCRA FIRST, MDR-HIV or another study which is not consistent with one of the treatment groups in the SMART study (e.g., ESPRIT or SILCAAT).
2. Current pregnancy or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to disease progression or death. (The events constituting “disease progression” are opportunistic events that are consistent with the 1993 CDC expanded surveillance definition for clinical AIDS. These events are defined in the CPCRA Clinical Events Handbook and in a paper describing event documentation and review procedures. Other Major Endpoints include: -Survival -Time to major cardiovascular events: myocardial infarction, coronary artery disease requiring treatment or an invasive procedure, or stroke. (These events are defined in the CPCRA Supplemental Events Handbook.) - Time to “serious” disease progression event, including death. A serious event for this protocol is defined as one of the following: progressive multifocal leukoencephalopathy, lymphoma, visceral Kaposi's sarcoma, AIDS dementia complex, toxoplasmosis, histoplasmosis, cryptococcosis, MAC, wasting syndrome, and cytomegalovirus disease. - Time to major cardiovascular or metabolic events: myocardial infarction (based on review of hospital records or serial ECG changes indicating major Q wave changes), coronary artery disease requiring treatment or an invasive procedure, myocarditis or pericarditis, stroke, diabetes mellitus, pancreatitis, lactic acidosis, or osteonecrosis (These events are defined in the CPCRA Supplemental Events Handbook.) Initiation of drug treatment for hypertension and hyperlipidemia will also be recorded. - Time to disease progression event, major cardiovascular event, major metabolic event, or death - Time to the development of any grade 4 adverse event - Change in self-reported body appearance - Time to developing new ST-T wave abnormalities, left ventricular hypertrophy, major arrhythmias, heart rate, heart rate corrected QT interval, complete heart block, LBBB, and RBBB based on the resting ECG - Health care utilization and costs - Change in total, LDL, VLDL, and HDL cholesterol; triglycerides, glucose, insulin, C-peptide, hemoglobin A1c, venous lactate, and in body cell mass as measured by BIA. - Change in quality of life - Symptom severity - Change in HIV transmission risk behaviors - Change in fat distribution as assessed by DEXA and CT scans - Self-reported adherence to antiretroviral drugs - Development of MDR HIV drug resistance (evidence of resistance to 2 or more classes of antiretroviral drugs) - Retroviral rebound syndrome |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
strategic study (see also sec.D2) |
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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) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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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The study will be event-driven. That is, following a 3.5-year enrollment period, follow-up will extend as long as necessary to obtain the required 910 primary events |
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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 | 7 |
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 | 9 |