Clinical trial NCT03968939
Conditions: Primary Total Hip Arthroplasty Primary Total Knee Arthroplasty
Sponsor: James A. Keeney
Start date: 2019-10-01; Completion date: 2022-05-22
Enrollment: 55 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To compare non-prescription sleep aids (low-dose diphenhydramine and melatonin) to sleep hygiene education for improving postoperative sleep quality after total joint arthroplasty.

Detailed description:

Arms: arm 1: Control Group (Usual Care): Participants do not use any type of sleep education or non-prescription sleep medications to assist with getting a "good night's sleep". arm 2: Sleep Hygiene Education: Participants are provided a Sleep Hygiene Education Brochure containing information about getting a "good night's sleep." arm 3: Participants are given both:

1. Over-the-counter sleep aids:25 mg Diphenhydramine (Benadryl) and 3mg oral melatonin to be taken before bedtime;
2. and a Sleep Hygiene Education Brochure containing information about getting a "good night's sleep."
Interventions: intervention 1: Diphenhydramine (Benadryl) intervention 2: Melatonin intervention 3: Sleep Hygiene Education
Intervention descriptions: intervention 1: Oral Diphenhydramine (Benadryl), 25 mg intervention 2: Oral Melatonin, 3 mg intervention 3: Brochure containing information about getting a "good night's sleep."

Protocol documents:
Prot_000.pdf: 
Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
1 
 
 
Proposal 
 
Postoperative Sleep Quality Following Total Joint Arthroplasty: A Prospective, 
Randomized, Controlled Trial of Diphenhydramine and Melatonin Versus Sleep 
Skills Training 
 
James A. Keeney, MD 
 
 
Background 
Sleep disruption is a common, yet oft-ignored, problem in patients before and 
after total joint arthroplasty (TJA) with a postoperative prevalence as high as 50%.1 
Postoperative sleep disturbance is often reciprocal to night pain and mediates the 
association between early postoperative pain and functional recovery following TJA.2 As 
such, optimizing sleep has potential to decrease pain and enhance a patient’s mental 
status during daytime hours after TJA, which may improve functional outcomes and 
hasten postoperative recovery.3 Inversely, persistent sleep disturbance after TJA may 
increase pain and jeopardize the postoperative course while straining the physician- 
patient relationship. 
 
The impact of sleep quality on postoperative functioning and recovery 
necessitates its optimization, especially in the context of exponentially increasing demand 
for TJA and an evolving healthcare landscape. By 2030, total hip arthroplasty (THA) 
utilization is projected to nearly triple from 2005 levels to almost 600,000 cases per year.4 
Demand for total knee arthroplasty (TKA) is also expected to increase over 650% from 
2005 levels to nearly 3.5 million cases annually.4 The utilization of patient satisfaction 
and outcome measures in reimbursement systems also continues to increase. Patient 
responses on such outcome measure tools can be impacted by their sleep quality, as it 
remains an important determinant of postoperative pain and functional recovery. This 
paradigm shift underlines the importance of optimizing all aspects of TJA patients’ 
postoperative course, including sleep quality. While previous studies have demonstrated 
sleep disturbance in the weeks and early months following TKA,2, 5-7 there is a paucity of 
studies which prospectively assess interventions for sleep optimization after primary 
THA and TKA. 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
2 
 
 
The purpose of this study is to compare the efficacy of non-prescription sleep medications 
(low-dose diphenhydramine and melatonin) to sleep hygiene education for improving sleep 
after primary elective total hip and knee arthroplasty. 
 
Objective: 
• To compare non-prescription sleep aids (low-dose diphenhydramine and 
melatonin) to sleep hygiene education for improving postoperative sleep quality 
after total joint arthroplasty 
 
Study Design: 
• Patient Population: 
o Sample size: 375 
o Inclusion criteria: all patients undergoing elective primary total hip or 
knee arthroplasty 
o Exclusion criteria: history of substance abuse, workman’s compensation 
patients, revision joint replacement, history of prescription or over-the- 
counter sleep aid use 
 
• Data To Be Collected: 
o Demographic data: gender, age, body mass index (BMI), alcohol 
consumption, tobacco use, narcotic use, previous diagnosis of sleep apnea 
o Perioperative data: Diagnosis, Operation, Laterality, American Society of 
Anesthesiologists (ASA) classification, Tourniquet time, Location of 
discharge (home vs rehabilitation facility), Length of stay 
o Postoperative data: Medications  
o Outcomes Data Collection Tools: 
 Epworth Sleepiness Scale (ESS) (Appendix 1) 
 Pittsburgh Sleep Quality Index (PSQI) (Appendix 2) 
 Visual Analogue Scale (VAS) for pain 
 Sleep Skills Handout (Appendix 3) 
 
• Study Methods and Logistics 
o Consenting patients scheduled for primary THA or TKA who meet the 
“patient population” criteria as noted above will be enrolled in the study at 
their preoperative clinic visit 
o Patients will be randomized  to one of three groups: 
 Control group (Usual Care) 
 Sleep Hygiene Education 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
3 
 
 
 Over-the-counter sleep aids (25 mg Benadryl + 3mg melatonin) + 
Sleep Hygiene Education 
o Data will be collected at: preoperative clinic visit at time of enrollment, 
and 3, 6, and 12 weeks postoperative (by phone or routine postoperative 
clinic visits) 
o Logistics for Benadryl + Melatonin Group + Sleep Hygiene Education 
 This group will be given their full supply of Benadryl (25mg) and 
Melatonin before being discharged, but will not start them until 
the first day home each day  until 12 weeks postoperative. 
 I can acquire department funding to supply the Benadryl and 
melatonin free of charge to patients, I met with pharmacy and they 
said the cost is nearly negligible for these medications. 
 This will be a handout (Appendix 3) that will be reviewed with 
patients at enrollment and 3, 6, and 12 weeks postoperative 
when the data is collected. 
o Logistics Sleep Hygiene Education Group 
 This will be a handout (Appendix 3) that will be reviewed with 
patients at enrollment and 3, 6, and 12 weeks postoperative 
when the data is collected. 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
4 
 
 
Appendix 1: Epworth Sleepiness Scale (ESS) 
 
How likely are you to doze off or fall asleep during the following situations, 
in contrast to just feeling tired? 
 
For each of the situations listed below, give yourself a score of 0 to 3, where 
0 = Would never doze; 1 = Slight chance; 2 = Moderate chance; 3 = High chance. 
 
Work out your total score by adding up your individual scores for situations 1 to 8. (If 
you have not been in the following situations recently, think about how you would have 
been affected.) 
 
Situation 
Score 
Sitting and reading 
 
Watching television 
Sitting inactive in a public place (e.g. a theatre/meeting) 
As a passenger in a car for an hour with no break 
Lying down in the afternoon (when possible) 
Sitting and talking to someone 
Sitting quietly after lunch without alcohol 
In a car, while stopped for a few minutes in traffic 
Total 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
5 
 
 
 
 
 
Appendix 2: Pittsburgh Sleep Quality Index (PSQI) 
 
Instructions: 
The following questions relate to your usual sleep habits during the past month only. 
Your answers should indicate the most accurate reply for the majority of days and nights 
in the past month. Please answer all the questions. 
 
1. During the past month, when have you usually gone to bed at night? 
 
usual bed time  
 
 
2. During the past month, how long (in minutes) has it usually taken you to fall asleep 
each night? 
 
number of minutes  
 
 
3. During the past month, when have you usually got up in the morning? 
 
usual getting up time  
 
 
4. During the past month, how many hours of actual sleep did you get at night? (This 
may be different than the number of hours you spend in bed). 
 
hours of sleep per night  
 
 
For each of the remaining questions, check the one best response. Please answer all 
questions. 
 
5. During the past month, how often have you had trouble sleeping because you…… 
 
(a) Cannot get to sleep within 30 minutes 
 
Not during the 
Less than 
Once or 
three or more 
past month  
once a week  
 
twice a week  
 
times a week  
 
 
(b) Wake up in the middle of the night or early morning 
 
Not during the 
Less than 
Once or 
Three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
(c) Have to get up to use the bathroom 
 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
6 
 
 
(d) Cannot breathe comfortably 
 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
(e) Cough or snore loudly 
 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
(f) Feel too cold 
 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
(g) Feel too hot 
 
Not during the 
past month  
 
Less than 
once a week  
 
Once or 
twice a week  
 
three or more 
times a week  
 
(h) Had bad dreams 
Not during the 
past month  
 
Less than 
once a week  
 
Once or 
twice a week  
 
three or more 
times a week  
 
(i) Have pain 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
(j)  Other reason(s), please describe  
 
 
 
How often during the past month have you had trouble sleeping because of this? 
 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
 
6. During the past month, how would you rate your sleep quality overall? 
 
Very good  
             
Fairly good  
           
Fairly bad  
               
Very bad  
 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
7 
 
 
 
7. During the past month, how often have you taken medicine (prescribed or “ over 
the counter”) to help you sleep? 
 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
8. During the past month, how often have you had trouble staying awake while 
driving, eating meals, or engaging in social activity? 
Not during the 
Less than 
Once or 
three or more 
past month  
 once a week  
 
twice a week  
 
times a week  
 
 
9. During the past month, how much of a problem has it been for you to keep up 
enough enthusiasm to get things done? 
 
No problem at all  
               
Only a very slight problem 
Somewhat   of   a    problem A 
very big problem  
 
 
10. Do you have a bed partner or roommate? 
 
No bed partner or roommate 
  
 
Partner/roommate in other room          
 
Partner in same room, but not same bed 
Partner in same bed 
  
 
 
11. How often do you feel tired during the following times during the day? 
 
Morning: 
0 
1 
2 
3 
most days 
often 
occasionally 
never 
 
Afternoon: 
0 
1 
2 
3 
most days 
often 
occasionally 
never 
 
Evening: 
0 
1 
2 
3 
most days 
often 
occasionally 
never 


Sleep Quality after Primary THA and TKA 
  Version 3 
  
 
 
        March 6, 2020 
8 
 
 
 
Appendix 3: Sleep Hygiene Education Handout 
 
https://www.kramesstore.com/index.php/abcs-of-zzzs-the-basics-of-sleep-health-nsf.html 
• I will look into department funding to buy these brochures to use as our handout 
(~$0.80 per brochure). They are published by the National Sleep Foundation and 
appear to be high quality. 
 
 
 
References 
 
1. Wylde V, Rooker J, Halliday L, Blom A: Acute postoperative pain at rest after hip and 
knee arthroplasty: Severity, sensory qualities and impact on sleep. Orthop Traumatol 
Surg Res 2011;97:139-144. 
 
2. Cremeans-Smith JK, Millington K, Sledjeski E, Greene K, Delahanty DL: Sleep 
disruptions mediate the relationship between early postoperative pain and later 
functioning following total knee replacement surgery. J Behav Med 2006;29:215-222. 
 
3. Hawker GA, Stewart L, French MR, et al: Understanding the pain experience in hip 
and knee osteoarthritis--an OARSI/OMERACT initiative. Osteoarthritis Cartilage 
2008;16:415-422. 
 
4. Kurtz S, Ong K, Lau E, Mowat F, Halpern M: Projections of primary and revision hip 
and knee arthroplasty in the united states from 2005 to 2030. J Bone Joint Surg Am 
2007;89:780-785. 
 
5. Krenk L, Jennum P, Kehlet H: Sleep disturbances after fast-track hip and knee 
arthroplasty. Br J Anaesth 2012;109:769-775. 
 
6. Er MS, Altinel EC, Altinel L, Erten RA, Eroglu M: An assessment of sleep quality in 
patients undergoing total knee arthroplasty before and after surgery. Acta Orthop 
Traumatol Turc 2014;48:50-54. 
 
7. Chen AF, Orozco FR, Austin LS, Post ZD, Deirmengian CA, Ong AC: Prospective 
evaluation of sleep disturbances after total knee arthroplasty. J Arthroplasty 2016;31:330- 
332.