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

NCT ID: NCT06807970

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-07-01

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GLP-1RA

Intervention group: GLP-1RA +TKR:

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.

Group Type: EXPERIMENTAL

Glucagon-like peptide-1 receptor agonists (GLP 1 RA)

Intervention Type: DRUG

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.

Control (standard treatment)

Control Group: TKR alone:

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.

Group Type: PLACEBO_COMPARATOR

Control (Standard treatment)

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age between 40 and 80 years old
• BMI ≥27 kg/m2
• On the surgical waiting list for primary TKR
• Willing and able to cooperate in a weight management programme.
• Meeting indication for semaglutide

Exclusion Criteria

• Revision surgery or surgery for neoplastic disease
• A medical condition which in the opinion of the investigators makes the patient unsuitable for participation in the trial
• Contraindication to GLP-1RA, like history of pancreatitis, severe gastrointestinal diseases such as gastroparesis, thyroid cancer, and inflammatory bowel disease
• Lack of acceptance of the randomisation process.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Prof Lawrence Lau

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lawrence Lau, FRCS, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Central Contacts

Lawrence Lau, FRCS, PhD

Role: CONTACT

laucml@hku.hk

+852 92646862

Other Identifiers

UW24-423

Identifier Type: -

Identifier Source: org_study_id