NCT06807970

Optimization of Obesity for Total Knee Replacement With Glucagon-like Peptide-1 Receptor Agonist

Novel Perioperative Optimization of Obese Osteoarthritic Patients Pending Total Knee Replacement With Glucagon-like Peptide-1 Receptor Agonist (NPO-OOPS-TKR)

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 40 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Studies have shown that obese patients undergoing total knee replacement (TKR) surgery face a higher risk of perioperative issues such as increased use of pain medication, surgical site infections, and the need for revision surgeries compared to non-obese patients. Obesity is also linked to more significant preoperative pain and lingering symptoms post-surgery. Consequently, there's a growing interest in weight loss interventions prior to TKR to enhance perioperative care and outcomes. Recent retrospective studies have indicated that such interventions can improve physical function post-TKR. Research focusing on weight loss interventions before joint replacement surgery is limited. There is currently a gap in research regarding RCTs on weight loss interventions using anti-obesity drugs before TKR, particularly in Asian populations. One promising avenue under exploration involves the use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) as anti-obesity medication before total knee replacement (TKR) surgery. However, there are currently no randomized controlled trials (RCTs) examining the effects of GLP-1RAs on knee arthroplasty outcomes. Large database studies have indicated that GLP-1RAs may decrease the likelihood of certain post-surgery complications but increase the risk of others. In summary, addressing obesity through weight loss interventions, particularly with GLP-1RAs, holds promise for improving outcomes in TKR patients. However, further research, including randomized controlled trials, is necessary to fully understand the effects of GLP-1RAs on perioperative outcomes and patient health.

Detailed description

2.1 Hypothesis Hypothesis for this pilot trial is conducting trial of GLP-1RA for perioperative optimization for TKR feasible. The null hypothesis for the full trial is that clinical, functional and quality of life (QoL) outcomes in obese patients undergoing TKR will not be improved if this is preceded by GLP-1 RA induced weight loss. 3\. Study objective The primary aims of this pilot study are 1) estimate adherence, tolerability and follow-up rates, 2) recruitment and management challenges. The secondary aims are to assess the effect of semaglutide for perioperative optimization in TKR and gather data to estimate the feasibility like tolerability and sample size for a future trial.

Conditions

• Osteoarthritis (OA) of the Knee

Interventions

Type	Name	Description
DRUG	Glucagon-like peptide-1 receptor agonists (GLP 1 RA)	Patients in intervention group will have GLP-1RA semaglutide for 48 weeks and then stops for one month before and after TKR following the latest anesthesia guideline for GLP-1RA. Followed by TKR They will continue semaglutide for 48 weeks during the post-operative follow-up period. This is decided based on balancing treatment effect of semaglutide, waiting time for TKR, and TKR follow-up requirement. In Hong Kong, waiting time for TKR would be \~4 years and so a period of 12 months treatment of semaglutide is reasonable. And in the STEP 6 trial, weight loss at week 52 (-12%) is similar to that in study end at week 68(-13·2%), and STEP5 trial showed maintaining semaglutide to week 104 could maintain weight loss of similar degree as in week 52. And the consensus of assessing TKR Patient-Reported Outcome Measures (PROMs) is one year follow up.
OTHER	Control (Standard treatment)	If patients are randomized to the control group, they will receive routine follow-up with general advice on diet and physical activity but will not receive semaglutide, and will not be offered a specific management program for their weight. This is in line with current practice.

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-07-01
• Completion: 2028-07-01
• First posted: 2025-02-04
• Last updated: 2025-09-03

Regulatory

• FDA-regulated drug study