Fig. 1.

Study design and subject disposition. The baseline visit (randomization) was arranged after the screening visit (visit 0). If a wash-out was not necessary, the patient could be admitted to visit 1 (baseline) on the same day as the screening visit, in which case attention had to be paid that all the procedures/assessments foreseen at the baseline visit were performed. The wash-out period was only needed if patients were taking analgesics/NSAIDs. The per-protocol (PP) population consisted of all patients in the intention-to-treat (ITT) population who did not have any major protocol violations. The PP population consisted of 341 patients in the HA-HL group and 340 in the placebo group; six patients in the HA-HL group and five in the placebo group had major protocol deviations, most commonly intake of a prohibited medication (n = 5) or violation of an exclusion criteria (n = 3)