Study design
pain
This was a randomized, double-blind, double-dummy, active-comparator non-inferiority study comprising three periods: screening period, treatment period, and follow-up period (Fig. Study design. The patient’s eligibility was checked during the screening period (up to 15 days). Patients used a 100-mm visual analog scale (VAS) to assess their pain at rest on study days − 2, − 1, and 1 (where study day 1 was the day of starting treatment); only patients with a score of ≥ 25 mm averaged over the 3 days were eligible. The dosing procedure in each group is described in more detail in the Supplementary Methods. Patients received a dose of 50 mg/day in the evening on study day 1, followed by 100 mg/day on study day 2. On study days 2–10, the tramadol dose could be escalated by 100 mg/day to a maximum of 300 mg/day. The dose could not be escalated between study days 11 and 14. Rescue medication was permitted throughout the treatment period. 