START study increases sample size: additional 600 participants to be older than 35

Simon Collins, HIV i-Base

The international START study is on track to enrol the last of the initially proposed 4000 participants by May 2013. However, an additional 600 patients are due to be enrolled, which will require fewer final events and still have the study reporting primary results within three years.

As detailed in the study protocol, a blinded assessment of the event rate and baseline entry criteria was performed to review whether the projected event rate in the two arms combined was matching actual events during the enrollment phase, in order to modify the study numbers if this has an impact on the power of the study.

This analysis showed that event rates are lower than originally estimated and this could imply that the persons enrolled are healthier than assumed. The ongoing safety of both arms is clearly supported by this low event rate. Enrolment of the last 600 persons older than 35 years will assist in raising the event rate.

Conversely, the CD4 count when entering the study was higher than projected. The wider difference in CD4 counts between the deferred and immediate arms than originally projected reduces the number of endpoints needed in order to answer the study question: only 213 rather than 370 endpoints will now be required to retain 90% power on the primary endpoint of the difference between the two approaches in serious AIDS and non-AIDS events including mortality.

Continued adherence to the two strategies in the next three years (i.e. immediate vs deferred initiation of ART) is now an important focus of the ongoing study.

The projected minimum follow-up time for START remains unchanged at three years, with result still expected in 2016. The next review by the study DSMB will be in May 2013.

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