Improving Sleep After TKA Using Mirtazapine and Quetiapine

Insomnia Clinical Trial

Official title:

Mirtazapine and Quetiapine as Treatment for Postoperative Sleep Disturbance After Fast-track Knee Replacement

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04728581
• Other study ID #: W021-001
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: January 1, 2027

Study information

• Verified date: June 2023
• Source: St. Anna Ziekenhuis, Geldrop, Netherlands
• Contact: Walter van der Weegen
• Phone: 06-34282788
• Email: w.vanderweegen[@]st-anna.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Use of mirtazapine and quetiapine for improvement of sleep quality after TKA

Description:

Background After knee replacement surgery there is a loss of quantity and quality of sleep. Loss of sleep is associated with increased pain perception. Subsequently, patients use more analgesic medication and it takes them longer to fully recover from surgery. Low doses of the tetracyclic antidepressant mirtazapine and the neuroleptic quetiapine are nowadays off-label prescribed for insomnia and improve length and quality of deep sleep phases. Quetiapine and mirtazapine could improve sleep after knee replacement surgery and improve patient recovery. This placebo-controlled, randomized, double-blind study investigates the effect of quetiapine and mirtazapine on functional recovery after total knee arthroplasty.

Methods This is a prospective, single center, double-blinded randomized controlled trial. 165 patients with knee osteoarthritis scheduled for total knee arthroplasty will be randomly allocated to a low-dose quetiapine (LDQ), a low-dose mirtazapine (LDM) group or a placebo group. Outcomes will be evaluated at baseline, 2, 4, 6 and 12 weeks after surgery. Functional outcome after total knee arthroplasty is measured using a patient related outcome measure through the Oxford Knee Score (OKS). In order to measure postoperative sleep quality, patients will be monitored using the Leeds Sleep evaluation questionnaire (LSEQ). Furthermore, pain is registered using a visual analogue scale (VAS), weekly opioid use is monitored, and general health status is reported through the EQ-5D. Analyses will be conducted on an intention-to-treat basis using logistic and linear mixed regression models. This trial complies with the SPIRIT guidelines for randomized controlled trials.

Discussion This study will provide clinicians with evidence whether quetiapine contributes to rehabilitation of patients undergoing fast-track knee replacement surgery.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 165
• Est. completion date: January 1, 2027
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Indication for TKA

Exclusion Criteria:

• use of benzodiazepines

• use of anti-depressants

• use of oxycodone

• patients diagnosed with obstructive sleep apnea syndrome, severe respiratory insufficiency, or myasthenia

• a known hypersensitivity to mirtazapine, quetiapine and/or related to the gelatinous (placebo) capsule

• insufficient understanding of the Dutch language.

Related Conditions & MeSH terms

• Insomnia
• Osteo Arthritis Knee
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Mirtazapine
Use of 3.75mg mirtazapine before lights-out during first 2 weeks after TKA surgery. With insufficient effect on sleep, patients are allowed to increase medication to 7.5mg mirtazapine.
• Quetiapine
Use of 3.125mg quetiapine before lights-out during first 2 weeks after TKA surgery. With insufficient effect on sleep, patients are allowed to increase medication to 6.25mg mirtazapine.
• Placebo
a gelatinous capsule without an active ingredient

Locations

Country	Name	City	State
Netherlands	Knowledge Center for Orthopedic Surgery, St. Anna hospital	Geldrop
Netherlands	St. Anna hospital	Geldrop

Sponsors (1)

Lead Sponsor	Collaborator
St. Anna Ziekenhuis, Geldrop, Netherlands

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxford Knee Score (OKS)	Validated functional knee score after TKA, minimum score 12 (best outcome), maximum score 60 (worst outcome)	6 weeks after surgery
Secondary	Leeds Sleep Evaluation questionnaire (LSEQ)	Validated sleep score in 3 dimensions of sleep	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	Visual Analogue Scale (VAS) for fatigue	Visual analogue reporting of fatigue after sleep, indicated on a 0 (best outcome) to 100 (worst outcome) mm line	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	Visual Analogue Scale (VAS) for sleep quality	Visual analogue reporting of quality sleep, indicated on a 0 (worst outcome) to 100 (best outcome) mm line	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	Visual Analogue Scale (VAS) for pain in rest	Visual analogue reporting of knee pain while resting, indicated on a 0 (best outcome) to 100 (worst outcome) mm line	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	Visual Analogue Scale (VAS) for pain during activity	Visual analogue reporting of knee pain during exercises, indicated on a 0 (best outcome) to 100 (worst outcome) mm line	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	EuroQol (EQ) 5D	General well being score, full health represented by 11111 score (overall score for the Netherlands of 1,000), worst health represented by 55555 score (overal score for the Netherlands of -0,329)	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	Morphine use	Total amount (mg) morphine use after surgery is documented	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
Secondary	Oxford knee score	Validated functional knee score after TKA, minimum score 12 (best outcome), maximum score 60 (worst outcome)	1 week before surgery; first day postoperative; 2; 4; 12 weeks after surgery