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It was a try from wing Napolioni Nalaga that made the difference for Clermont, who had featured in every French final since 2007 without success, and the boot of Morgan Parra did the rest of the damage.
First-half tries from British & Irish Lions Tommy Bowe and Lee Byrne provided the Ospreys with the impetus they needed to win at the RDS.
Meanwhile, more than 80,000 packed into the 2012 Heineken Cup final venue, Twickenham Stadium, to see Leicester Tigers snatch victory from the jaws of defeat in a sensational 33-27 triumph against Saracens.
Their win meant that three national champions emerged from the Pool 3 of the 2009/2010 Heineken Cup draw - ASM Clermont Auvergne, Ospreys and Leicester Tigers.
The Italian Super 10 title went to Benetton Treviso thanks to their 16-12 victory over Viadana in Rome.
