E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 |
Based on two scientific hypotheses, both which take advantage of the randomized design of START and the extended follow-up through 2021, the primary objective is to determine whether the benefit of early ART as compared to deferred ART in delaying the occurrence of a composite outcome consisting of AIDS, non-AIDS, or death from any cause is maintained, increased or reduced. |
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E.2.2 | Secondary objectives of the trial |
To compare early ART to deferred ART for the following secondary outcomes: All-cause mortality, ESRD (initiation of dialysis, renal transplantation), Decompensated liver disease, Non-AIDS malignancy, including basal and squamous cell skin cancers, AIDS, Bacterial pneumonia, Adverse events, Hospitalization, Quality of life (through December 2015), Health-care utilization and cost of care (through December 2015), HIV transmission risk behavior (through December 2015), HIV drug resistance, Pulmonary embolism or deep vein thrombosis, New-onset diabetes mellitus, Coronary artery disease requiring drug treatment, Congestive heart failure, Peripheral arterial disease, Change in estimated GFR and development of proteinuria, Blood pressure and blood lipids, ECG abnormalities (through December 2016), Use of blood pressure- or lipid-lowering treatment or aspirin, Fractures |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The pulmonary substudy, version 1.0, 2009Oct22: The primary objective of this substudy is to determine if immediate initiation of ART alters the rate of lung function decline compared to deferral of ART until the CD4+ declines below 350 cells/mm3 in HIV-1 infected persons who are antiretroviral naïve with a CD4+ count above 500 cells/mm3. Furthermore, the obejctive is to determine if immediate ART alters respiratory health status compared to deferred ART. |
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E.3 | Principal inclusion criteria |
All HIV-positive participants in START are eligible to continue in extended follow-up |
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E.4 | Principal exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
AIDS* or death from AIDS Opportunistic events consistent with the 1993 CDC expanded surveillance definition plus additional events associated with immunosuppression in the patient population targeted for enrollment. Esophageal candidiasis and chronic Herpes simplex infection will be counted as primary endpoints only if they result in death.Non-AIDSCVD: myocardial infarction, stroke, coronary revascularizationESRD: initiation of dialysis, renal transplantationDecompensated liver diseaseNon-AIDS-defining cancers, excluding basal and squamous cell skin cancers. Basal and squamous cell skin cancer will be counted as a primary endpoint only if they result in death.Death not attributable to AIDS, including death of unknown causeThe primary outcome of START and each of the major components of the primary outcome will be evaluated as the time to the first occurrence of an event above. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be assessed as part of the extended follow-up. All of these endpoints have been assessed since the beginning of the START trial in 2009; therefore, the two treatment strategies will be compared for the following three calendar periods: 1) from randomization to December 31, 2015; 2) from January 1, 2016 to December 31, 2021; and 3) cumulatively from randomization through 2021 |
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E.5.2 | Secondary end point(s) |
Separate components of the composite outcome; all-cause mortality; all AIDS events (including esophageal candidiasis and chronic Herpes simplex); all non-AIDS-defining cancers (including basal and squamous cell skin cancers); bacterial pneumonia; pulmonary embolism; deep vein thrombosis; new-onset diabetes mellitus; coronary artery disease requiring drug treatment; congestive heart failure; peripheral vascular disease; fractures; and adverse events. In addition Quality of Life; health care utilization; health care cost; transmission risk behavior; drug resistance & markers of CVD. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be assessed as part of the extended follow-up. All of these endpoints have been assessed since the beginning of the START trial in 2009; therefore, the two treatment strategies will be compared for the following three calendar periods: 1) from randomization to December 31, 2015; 2) from January 1, 2016 to December 31, 2021; and 3) cumulatively from randomization through 2021 |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Initiated on recent guidelines, now started on therapy vs. immediate therapy |
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Chile |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
India |
Ireland |
Israel |
Italy |
Luxembourg |
Malaysia |
Mali |
Mexico |
Morocco |
Nigeria |
Norway |
Peru |
Poland |
Portugal |
Singapore |
South Africa |
Spain |
Sweden |
Switzerland |
Thailand |
Uganda |
United Kingdom |
United States |
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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
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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 | 11 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 11 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |