Improving Sleep After TKA Using Mirtazapine and Quetiapine

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Osteo Arthritis Knee; Insomnia
• Intervention / Treatment: Drug: Placebo; Drug: Mirtazapine; Drug: Quetiapine

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 Type: Interventional
• Enrollment (Estimated): 165
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Walter van der Weegen; Phone Number: 06-34282788; Email: w.vanderweegen@st-anna.nl
• Study Contact Backup: Name: Michiel Siebelt

Study Locations

• Netherlands
  • Geldrop, Netherlands
    • St. Anna Hospital
    • Contact: Walter van der Weegen; Phone Number: 06-34282788; Email: w.vander.weegen@st-anna.nl
  • Geldrop, Netherlands
    • Knowledge Center for Orthopedic Surgery, St. Anna hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; use of placebo during first 2 weeks after TKA surgery	Drug: Placebo; a gelatinous capsule without an active ingredient
Experimental: Low dose Mirtazapine; Use of Mirtazapine 3.75mg before lights-out, allowed to increase medication to 7.5mg	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.
Experimental: Low dose Quetiapine; use of Quetiapine 3.125mg before lights-out, allowed to increase medication to 6.25mg	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: St. Anna Ziekenhuis, Geldrop, Netherlands

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 23, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Quetiapine Fumarate; Mirtazapine
• Other Study ID Numbers: W021-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data free accessible upon request
• IPD Sharing Time Frame: First year after publication
• IPD Sharing Access Criteria: After written request, and received permission
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No