Improving Sleep After TKA Using Mirtazapine and Quetiapine

Not Applicable

Not yet recruiting

• Conditions: Osteo Arthritis Knee; Insomnia
• Interventions: Drug: Placebo; Drug: Mirtazapine; Drug: Quetiapine

• Registration Number: NCT04728581
• Lead Sponsor: St. Anna Ziekenhuis, Geldrop, Netherlands

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2021-01-12
• Study First Submitted QC: 2021-01-23
• Study First Posted: 2021-01-28
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-01
• Last Update Posted: 2023-06-02
• Study Start: 2024-01-01
• Primary Completion: 2026-05-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 165

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	use of placebo during first 2 weeks after TKA surgery
Low dose Mirtazapine	Mirtazapine	Use of Mirtazapine 3.75mg before lights-out, allowed to increase medication to 7.5mg
Low dose Quetiapine	Quetiapine	use of Quetiapine 3.125mg before lights-out, allowed to increase medication to 6.25mg

Primary Outcome Measures

Name	Time	Method
Oxford Knee Score (OKS)	6 weeks after surgery	Validated functional knee score after TKA, minimum score 12 (best outcome), maximum score 60 (worst outcome)

Secondary Outcome Measures

Name	Time	Method
Visual Analogue Scale (VAS) for pain in rest	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	Visual analogue reporting of knee pain while resting, indicated on a 0 (best outcome) to 100 (worst outcome) mm line
Oxford knee score	1 week before surgery; first day postoperative; 2; 4; 12 weeks after surgery	Validated functional knee score after TKA, minimum score 12 (best outcome), maximum score 60 (worst outcome)
Leeds Sleep Evaluation questionnaire (LSEQ)	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	Validated sleep score in 3 dimensions of sleep
Visual Analogue Scale (VAS) for fatigue	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	Visual analogue reporting of fatigue after sleep, indicated on a 0 (best outcome) to 100 (worst outcome) mm line
Visual Analogue Scale (VAS) for sleep quality	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	Visual analogue reporting of quality sleep, indicated on a 0 (worst outcome) to 100 (best outcome) mm line
Visual Analogue Scale (VAS) for pain during activity	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	Visual analogue reporting of knee pain during exercises, indicated on a 0 (best outcome) to 100 (worst outcome) mm line
Morphine use	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	Total amount (mg) morphine use after surgery is documented
EuroQol (EQ) 5D	1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery	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)

Trial Locations

Locations (2)

St. Anna hospital; 🇳🇱 Geldrop, Netherlands

Knowledge Center for Orthopedic Surgery, St. Anna hospital; 🇳🇱 Geldrop, Netherlands