Optimizing post operative outcomes in Total Knee Arthroplasty (TKR) through improved pain and fatigue management: a randomized placebo controlled trial.

This study is a multi-centered prospective, blinded, randomized, placebo controlled trial. There are four treatment arms; placebo, temazapam, amitryptyline, and pregabalin. Patients randomized to the placebo group will be given a single tablet administered orally once daily in the evening(NOCTE) for six weeks. Patients randomized to the pregabalin group will be given 150mg/300mg pregabalin orally once daily (NOCTE) from day of surgery to six weeks post operatively. Patients randomized to the temazepam group will receive 10mg/20mg once daily (NOCTE) from the day of surgery to day 14 post operatively. Patients randomised to the amitrypyline group will receive 10mg/25mg once daily in the evening from the day of surgery to six weeks post operatively. All treatment arms will follow a rule; patients under 70 years of age and over 70kg in weight will receive the larger dose (McEwen 70/70). E.g. Patient #01 is 61 years old and weighs 86kg, therefore they will receive the larger dose provided for their specific treatment arm. Recruitment criteria for the study includes patients undergoing TKR. The consenting patients will be randomized to one of the four aforementioned arms. Patients will undergo the standard TKR procedure and receive post operative analgesia as per surgeons peri-operative protocol. Sleep function will be assessed by a validated questionnaire called the Pittsburgh sleep quality index. Pain will be assessed using validated pain scores. Knee function will be assessed using the 'WOMAC' knee score. Patients will be assessed using these scores and range of motion assessed preoperatively, at two weeks, six weeks and 3 months, and six months post-operatively. Patients who are identified as sleeping and coping poorly (PSQI > 5) will be considered for change of management. Placebo patients will be randomised to a treatment arm, patients already in a treatment arm will have the dosage increased if suitable or will be changed to another treatment arm. Adherence will be monitored by patient questionnaire and by drug tablet return and pill count at the two week and 6 week review.