Clinical trial NCT04728581: Improving Sleep After TKA Using Mirtazapine and Quetiapine
Official title: Mirtazapine and Quetiapine as Treatment for Postoperative Sleep Disturbance After Fast-track Knee Replacement
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Osteo Arthritis Knee
Insomnia
Lead sponsor: St. Anna Ziekenhuis, Geldrop, Netherlands
Sponsor class: OTHER
First posted: 2021-01-28
Enrollment: 165
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Oxford Knee Score (OKS)
timeFrame: 6 weeks after surgery
Secondary outcomes:
measure: Leeds Sleep Evaluation questionnaire (LSEQ)
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: Visual Analogue Scale (VAS) for fatigue
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: Visual Analogue Scale (VAS) for sleep quality
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: Visual Analogue Scale (VAS) for pain in rest
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: Visual Analogue Scale (VAS) for pain during activity
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: EuroQol (EQ) 5D
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: Morphine use
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 6; 12 weeks after surgery
measure: Oxford knee score
timeFrame: 1 week before surgery; first day postoperative; 2; 4; 12 weeks after surgery
Other outcomes:
Locations:
city: Geldrop
country: Netherlands
facility: Knowledge Center for Orthopedic Surgery, St. Anna hospital
city: Geldrop
country: Netherlands
facility: St. Anna hospital
Study officials:
References: