The accident happened around 4:00 a.m. Friday on the northbound lanes of the highway near Edgemoor Road.
Police say traffic had backed up from a previous crash nearby on I-95 at Philadelphia Pike in Claymont when the box truck rear ended the tractor-trailer, sending the rig into another tractor-trailer.
The driver of the box truck, identified as Edwin W. Trill Jr., 32, of Ridley Park, Pennsylvania, was trapped in the truck for about 30 minutes. He sustained serious head and chest injuries and went into cardiac arrest after being extricated from the vehicle. He was flown to Christiana Hospital where he died shortly after arrival.
The driver of the tractor trailer hit by the box truck, 59-year-old Alvin Flaud of Honey Brook, Pa., sustained head, abdominal and back injuries. He was also transported to Christiana Hospital and admitted in stable condition.
The driver of the other tractor-traler, 68-year-old Bryan Colon of Washington, North Carolina, was not injured.
The preliminary investigation indicates that Trill was not wearing his seatbelt. It is unknown at this time whether drugs or alcohol were a factor in the crash.
I-495 northbound was closed for approximately four hours while the crash was investigated and cleared.
