A Phase 4 interventional study of Doxepin 6 mg and Ramelteon 8 mg in Sleep Quality Post-TKA, Postoperative Knee Function and Quality of Life After Primary TKA, sponsored by University of Washington. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-05-20.
Sponsored by University of Washington · Phase 4, Interventional, and Supportive care
Many patients experience poor sleep during recovery after total knee arthroplasty (TKA). Disturbed sleep can last weeks to months and may worsen pain, slow healing, and reduce overall quality of life. Few safe, effective, evidence-based options exist to improve sleep during this recovery period. This study aims to determine whether the medications doxepin, either alone or in combination with ramelteon, can improve sleep quality during early recovery after TKA. The investigators will also evaluate whether improved sleep leads to better pain control, knee function, and overall quality of life.
This randomized, placebo-controlled clinical trial seeks to answer the following question: Is doxepin or combination therapy consisting of doxepin plus ramelteon superior to placebo in terms of (1) sleep quality as measured by the Insomnia Severity Index, (2) postoperative knee function as measured by KOOS-JR, KOOS-PS, or (3) overall health-related quality of life during the first three months after total knee arthroplasty.
University of Washington is the lead sponsor of 1,397 studies on the registry; 225 are open to participants now.
Of its 154 completed or terminated interventional studies of FDA-regulated products, 132 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants receive doxepin 6 mg and matching placebo orally once nightly for sleep during the first 6 weeks postoperative period following total knee arthroplasty.
Drug: Doxepin 6 mg
Participants receive doxepin 6 mg and ramelteon 8 mg orally once nightly for sleep during the first 6 weeks postoperative period following total knee arthroplasty.
Drug: Doxepin 6 mg · Drug: Ramelteon 8 mg
Participants receive 2 matching placebos orally once nightly for sleep during the first 6 weeks postoperative period following total knee arthroplasty.
Drug: Placebo Tablets
Doxepin 6 mg administered orally once nightly for sleep during the first 6 weeks of the postoperative period following total knee arthroplasty
Ramelteon 8 mg administered orally once nightly for sleep during the first 6 weeks of the postoperative period following total knee arthroplasty
Placebo administered orally once nightly for sleep during the first 6 weeks of the postoperative period following total knee arthroplasty
Insomnia Severity Index (ISI) scores (sleep quality)
Insomnia Severity Index (ISI) The Insomnia Severity Index is a 7-item self-reported questionnaire assessing the nature, severity, and impact of insomnia. * Score range: 0 to 28 * Interpretation: Higher scores indicate worse insomnia severity Score categories: * 0-7: No clinically significant insomnia * 8-14: Subthreshold insomnia * 15-21: Clinical insomnia (moderate severity) * 22-28: Clinical insomnia (severe)
Time frame: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively
Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS)
Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS): The KOOS-PS is a 7-item patient-reported outcome measure assessing knee-related physical function, including activities such as rising from bed, putting on socks, rising from sitting, bending to the floor, twisting/pivoting, kneeling, and squatting . Each item is scored on a 5-point Likert scale (None to Extreme). Scores are transformed to a normalized scale ranging from 0 to 100, with higher scores indicating worse physical function (greater disability).
Time frame: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively.
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR)
Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR): The KOOS-JR is a patient-reported outcome measure assessing knee pain, stiffness, and functional limitations during activities of daily living over the past week, including tasks such as twisting/pivoting, stair navigation, standing, rising from sitting, and bending . The instrument consists of 7 items scored on a 5-point Likert scale (None to Extreme). Raw scores (range 0-28) are summed and converted to an interval score ranging from 0 to 100, where 0 represents total knee disability and 100 represents perfect knee health (higher scores indicate better outcomes)
Time frame: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively
Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10)
Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10): The PROMIS-10 is a 10-item patient-reported outcome measure assessing global physical health, mental health, pain, fatigue, and social functioning. Items are scored on 5-point Likert scales (e.g., Excellent to Poor; Not at all to Very much), with one pain item scored from 0 to 10. Raw scores are summed and converted to standardized T-scores for Global Physical Health and Global Mental Health, each ranging approximately from 0 to 100 (mean 50, standard deviation 10), where higher scores indicate better health status
Time frame: Baseline; 2 weeks postoperatively; 6 weeks postoperatively; 3 months postoperatively
90-Day Hospital Readmission Status
Hospital readmission status within 90 days following primary total knee arthroplasty, defined as any unplanned inpatient admission to a hospital occurring within 90 days after the index procedure. This is a dichotomous outcome (Yes/No), where "Yes" indicates that a readmission occurred and represents a worse outcome.
Time frame: Within 90 days postoperatively
Medication Compliance
Medication Compliance: Medication adherence assessed using patient self-report and pill counts when feasible. Self-reported adherence is measured by patient-reported proportion of prescribed doses taken, and pill counts are used to calculate the percentage of medication consumed relative to the prescribed amount. Adherence is expressed as a percentage from 0 to 100%, where higher values indicate better compliance.
Time frame: 2 weeks postoperatively; 6 weeks postoperatively
Length of Stay (LOS)
Length of Stay (LOS): Length of hospital stay following primary total knee arthroplasty, defined as the number of days from hospital admission to discharge (continuous variable, ≥0 days), where higher values indicate longer hospitalization (worse outcome).
Time frame: Perioperative/Periprocedural
Discharge Destination
Discharge Destination: Discharge disposition following primary total knee arthroplasty, categorized as home versus skilled nursing facility. This is a categorical outcome where discharge to a skilled nursing facility represents a worse outcome compared to discharge home.
Time frame: Perioperative/Periprocedural
Postoperative Mobility (Step Count)
Postoperative Mobility (Step Count): Postoperative mobility assessed by the number of steps taken during inpatient physical therapy sessions following primary total knee arthroplasty. Step count is recorded as the total number of steps ambulated (continuous variable, ≥0), where higher values indicate better functional recovery.
Time frame: Perioperative/Periprocedural
Level of Assistance Required for Ambulation
Level of Assistance Required for Ambulation: Level of assistance required during inpatient physical therapy following primary total knee arthroplasty, categorized as independent, 1-person assist, 2-person assist, or maximal assist. This is an ordinal outcome where greater assistance requirements indicate worse functional recovery.
Time frame: Perioperative/Periprocedural
Postoperative Falls
Postoperative Falls: Occurrence of patient falls during hospitalization or within the follow-up period after primary total knee arthroplasty, defined as any unintentional descent to the ground or lower level documented in the medical record. This is a dichotomous outcome (Yes/No), where "Yes" indicates a fall occurred and represents a worse outcome.
Time frame: Perioperative/Periprocedural; 3 months postoperatively
Postoperative Delirium
Occurrence of delirium during hospitalization or follow-up after primary total knee arthroplasty, defined by clinical documentation of acute confusional state or use of delirium-related precautions (e.g., 1:1 sitter, physical restraints). This is a dichotomous outcome (Yes/No), where "Yes" indicates delirium occurred and represents a worse outcome.
Time frame: Perioperative/Periprocedural; 3 months postoperatively
Pressure Ulcers (Bed Sores)
Pressure Ulcers (Bed Sores): Development of pressure ulcers during hospitalization or follow-up after primary total knee arthroplasty, defined as localized injury to the skin or underlying tissue documented in the medical record. This is a dichotomous outcome (Yes/No), where "Yes" indicates a pressure ulcer occurred and represents a worse outcome.
Time frame: Perioperative/Periprocedural; 3 months postoperatively
Postoperative Opioid Consumption (Morphine Milligram Equivalents)
Postoperative Opioid Consumption (Morphine Milligram Equivalents): Total postoperative opioid use following primary total knee arthroplasty, calculated as cumulative morphine milligram equivalents (MME) administered during hospitalization and follow-up. This is a continuous variable (≥0 mg), where higher values indicate greater opioid consumption (worse outcome).
Time frame: Perioperative/Periprocedural; 3 months postoperatively
Postoperative Medical Complications
Postoperative Medical Complications: Occurrence of medical complications following primary total knee arthroplasty, including myocardial infarction, venous thromboembolism, cerebrovascular accident, acute kidney injury, respiratory failure, urinary tract infection, pneumonia, gastrointestinal obstruction, and need for intensive care unit (ICU) admission during the same hospitalization. This is a composite dichotomous outcome (Yes/No), where "Yes" indicates that one or more complications occurred and represents a worse outcome.
Time frame: Perioperative/Periprocedural
Postoperative Surgical Complications
Occurrence of surgical complications following primary total knee arthroplasty, including reoperation, periprosthetic fracture, dislocation, infection, and postoperative stiffness. This is a composite dichotomous outcome (Yes/No), where "Yes" indicates that one or more complications occurred and represents a worse outcome.
Time frame: Perioperative/Periprocedural; 3 months postoperatively
Plan to share: No
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Washington