Shortly after 3:15 a.m., police said a Durham County ambulance was on its way to a call when a Nissan Pathfinder crossed the center line and slammed into it head-on, causing it to flip on its side.
The crash happened on Lakewood Avenue and University Drive.
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The driver of the Nissan and two paramedics were taken to Duke University Hospital with minor injuries.
Officers said no patients were on board the ambulance during the crash.