Clinical trial NCT04380090
Conditions: Constipation
Keywords: constipation postoperative total knee arthroplasty
Sponsor: The Cleveland Clinic
Start date: 2020-02-21; Completion date: 2020-07-15
Enrollment: 154 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Postoperative constipation, defined as no fully satisfying bowel movement within the first three postoperative days, is a common occurrence with some researchers estimating that between 41 and 85% of postoperative patients experience symptoms. Causes include intraoperative medications, postoperative opioid analgesics, decreased mobility, and decreased oral intake. Constipation significantly impacts quality of life following surgery. Current standard of care for preventing postoperative constipation for patients having a single total knee arthroplasty at Cleveland Clinic is discharge on postoperative day one with either a prescription to be filled for docusate sodium (brand name Colace®) 100 mg to be taken two times a day by mouth for twenty eight days or the filled prescription, plus discharge instructions on ways to avoid and treat constipation. Research results show that docusate sodium is ineffective for preventing postoperative constipation in orthopedic surgery patients, and anecdotal reports confirm this finding. The proposed study uses a 2-group non-equivalent cohort design to evaluate the effect of one standard dose (17 grams) of an over-the-counter osmotic laxative (propylene glycol (PEG 3350), brand name Miralax) by mouth prior to discharge to the current standard of care. The primary outcome measure is whether patients report of a fully satisfying, normal for them, bowel movement within the first three postoperative days. Patient reported data will be collected by phone call four to seven days following surgery. Pertinent patient characteristics will be abstracted from the electronic medical record. The sample will consist of patients over twenty years old having a single total knee arthroplasty by Drs. Stearns, Molloy, or Murray who are admitted to unit 5D at Cleveland Clinic Lutheran Hospital postoperatively. Intent to treat analysis will be performed using logistic and linear regression models, adjusting for differences between groups on patient and surgical characteristics. Based on use of a two-sided Pearson chi-square test with 80% power and significance level of 0.05, 49 patients per group are required to detect a 25% decrease in constipation rate. To account for attrition we will over sample by 50% for a total of 74 per group or 148 total participants.

Detailed description:

Arms: arm 1: Docusate sodium one pill to be taken twice a day by mouth for 28 days arm 2: One standard dose (17 grams) of propylene glycol by mouth on postoperative day one
Interventions: intervention 1: Propylene Glycol intervention 2: Docusate Sodium
Intervention descriptions: intervention 1: Patients in the propylene glycol arm will receive one standard dose of the drug on postoperative day one prior to discharge with the aim of decreasing rates of postoperative constipation for patients following single total knee replacement surgery intervention 2: Patients in the docusate sodium arm are receiving the current standard of care for prevention of postoperative constipation following single total knee replacement surgery, docusate sodium one pill twice a day by mouth for 28 days

Protocol documents:
Prot_SAP_000.pdf: 
 
1 
 
 
Efficacy of One Dose of Laxative on Post-Operative Constipation following Total Knee 
Arthroplasty 
 
Kathleen Gonzalez, MSN, RN – Principal Investigator 
Karen Sanchez, ADN, RN – Co-Investigator 
Macy Mruk, BSN, RN – Co-Investigator 
Christian N. Burchill, PhD, MSN, RN, CEN – Research Mentor/Co-Investigator 
Cleveland Clinic, Cleveland Ohio 
 
 
 
NCT04380090   Unique Protocol ID: 20-080 
 
2/17/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Abstract 
Postoperative constipation, defined as no fully satisfying bowel movement within the first 
three postoperative days, is a common occurrence with some researchers estimating that 
between 41 and 85% of postoperative patients experience symptoms. Causes include 
intraoperative medications, postoperative opioid analgesics, decreased mobility, and decreased 
oral intake. Constipation significantly impacts quality of life following surgery. Current standard 
of care for preventing postoperative constipation for patients having a single total knee 
arthoplasty at Cleveland Clinic is discharge on postoperative day one with either a prescription 
to be filled for docusate sodium (Colace®) 100 mg to be taken two times a day by mouth for 
twenty eight days or the filled prescription, plus discharge instructions on ways to avoid and 
treat constipation. Research results show that docusate sodium is ineffective for preventing 
postoperative constipation in orthopedic surgery patients, and anecdotal reports confirm this 
finding. The proposed study uses a 2-group non-equivalent cohort design to evaluate the effect 
of one standard dose (17 grams) of an over-the-counter osmotic laxative (propylene glycol 
(PEG 3350), brand name Miralax) by mouth prior to discharge to the current standard of care. 
The primary outcome measure is whether patients report of a fully satisfying, normal for them, 
bowel movement within the first three postoperative days. Patient reported data will be collected 
by phone call four to seven days following surgery. Pertinent patient characteristics will be 
abstracted from the electronic medical record. The sample will consist of patients over twenty 
years old having a single total knee arthroplasty by Drs. Stearns, Molloy, or Murray who are 
admitted to unit 5D at Cleveland Clinic Lutheran Hospital postoperatively. Intent to treat analysis 
will be performed using logistic and linear regression models, adjusting for differences between 
groups on patient and surgical characteristics. Based on use of a two-sided Pearson chi-square 
test with 80% power and significance level of 0.05, 49 patients per group are required to detect 
a 25% decrease in constipation rate. To account for attrition we will oversample by 50% for a 
total of 74 per group or 148 total participants. 
 


 
3 
Constipation following orthopedic surgery is a common problem. Postoperative 
constipation is defined in the literature as no normal bowel movement within the first three 
postoperative days following surgery (Li et al., 2017; Trads, Deutch, & Pedersen, 2017; Turan & 
Asti, 2016). Estimates of postoperative constipation following orthopedic surgery range from 
41% to 85% of patients experiencing this uncomfortable side effect (Davies, Green, Mottram, & 
Pirmohamed, 2008; Şendir, Büyükyilmaz, Aşti, Gürpnar, & Yazgan, 2012; Stienen et al., 2014). 
Constipation has a negative impact on quality of life following orthopedic surgery (Jing & Jia, 
2019; Turan & Asti, 2016). Symptoms of postoperative constipation include abdominal pain, 
nausea, abdominal bloating, and difficulty passing hard stool (Turan & Asti, 2016). Despite the 
frequency of this problem and its impact on quality of life following orthopedic surgery, there is a 
dearth of rigorous scientific literature addressing preventative interventions. 
The majority of research studies addressing postoperative constipation prevention and 
treatment use orthopedic surgery patients as their population of interest, test non-
pharmacological interventions, and have relatively small sample sizes with no a priori sample 
size calculation noted in the manuscript. Regardless, results indicate that nursing interventions 
often work better than standard of care. In a quasi-experimental study examining the impact of 
development of a personalized postoperative constipation prevention care plan (helping patients 
figure out how they can increase fluids and fiber in their diet) for hip fracture surgery patients, 
researchers found that constipation rates were lower for those that used the individualized care 
planning process (Trads et al., 2017). Abdominal massage has also been tested as a non-
pharmacological intervention to treat postoperative constipation. Study results from two quasi-
experimental studies, orthopedic surgery patients in one study (Turan & Asti, 2016) and lung 
transplant patients in the other (Li et al., 2017), indicate that abdominal massage was superior 
to the existing standard of care at the study sites for preventing postoperative constipation. 
Turan and Asti’s (2016) abdominal massage intervention was superior to a pharmacological 
standard of care treatment, either a rectally administered laxative suppository or saline enema. 
Interestingly, results for time to first normal stool were past the defined time limit for 
postoperative constipation of surgical day three. 
Studies testing pharmacological interventions for prevention of postoperative 
constipation in the orthopedic surgery population also tend to have small sample sizes, yet 
results indicate significant differences between groups. Traditional preoperative mechanical 
bowel prep has been investigated as a postoperative constipation preventative intervention. A 
randomized controlled three arm trial investigated the efficacy of mechanical bowel prep using 
enema or suppository laxative versus the standard of care (no bowel prep) on postoperative 
constipation following spinal surgery. Sample sizes were small, 15 in each arm, yet results 
showed that time to bowel movement was shorter to a significant degree for those in the no 
bowel prep arm (Olsen et al., 2016). Researchers found in a pilot study (n=14) testing the 
feasibility of administering daily polyethylene glycol (PEG 3350 or brand name Miralax) versus 
daily oral docusate sodium (Brand name Colace) to prevent postoperative constipation 
following knee or hip arthroplasty a significant improvement in constipation rates with the PEG 
3350 group having a bowel movement one day sooner before postoperative day four (Madsen, 
Magor, & Parker, 2010).  As in the Madsen, Magor, and Parker study (2010), the current 
standard of care for preventing constipation for patients having knee or hip arthroplasty at 
Lutheran Hospital is a prescription for docusate sodium100 mg orally twice daily on discharge. 


 
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Docusate is one of the most often prescribed drugs for constipation prevention for 
hospitalized patients, but is essentially ineffective in preventing or relieving constipation (Fakheri 
& Volpicelli, 2019). Guidelines issued by The American Society of Colon and Rectal Surgeons 
(Paquette, et al, 2016) and a technical review issued by the American Gastroenterological 
Association (Bharucha, Pemberton, & Locke, 2013) both recommend the non-prescription 
osmotic laxative PEG 3350 over most other laxatives as it relieves constipation sooner than 
other treatments and is generally well-tolerated since it is not systematically absorbed. Results 
from a systematic review show that PEG 3350 performs better than another osmotic laxative 
(lactulose) at relieving constipation (Lee-Robichaud, Thomas, Morgan, & Nelson, 2010). 
Although none of these studies and guidelines specifically address the effectiveness of PEG 
3350 on postoperative constipation, they demonstrate that PEG 3350 is the gold standard in 
laxatives. 
Purpose 
The purpose of this study is to determine if one dose of an over-the-counter laxative 
administered on postoperative day one is more effective at preventing postoperative 
constipation, no fully satisfying bowel movement in the first three postoperative days, than an 
over-the-counter stool softener taken two times a day by mouth for twenty eight days. The 
primary research question to be answered is: 
What is the effect of one standard 17 gram dose of PEG 3350 given by mouth prior to 
discharge from single total knee arthroplasty surgery compared to current standard of care on 
frequency of postoperative constipation, defined as no fully satisfying bowel movement by 
postoperative day three? 
Secondary research questions are: 
 
What is the effect of one 17 gram dose of PEG 3350 given by mouth prior to discharge 
from total knee arthroplasty surgery compared to current standard of care on patient reported: 
 
Pain with bowel movement? 
 
Straining with bowel movement? 
 
Laxative use? 
Method 
This study uses a 2-group non-equivalent cohort design. Patients in cohort one will 
receive the current standard of care, a prescription for Colace to be taken twice a day for 28 
days. Once the sample size needed for group comparisons has been reached, prescribing 
practices will change. Patients in cohort two will receive one standard dose (17 grams) of 
Miralax by mouth on postoperative day one. Both groups will receive the current standard 
discharge instructions. 
Setting and Sample 
The study will be conducted at Cleveland Clinic Lutheran Hospital on unit 5D, a 42 bed 
telemetry-capable inpatient unit in which the majority of patients have had either orthopedic or 
general surgery. Follow up phone calls will be made to study participants using the phone 
number they provide, and the setting for answering these questions is of participant’s choosing. 
The sample of patients for this study must meet the following criteria: 
 
Admission to Lutheran Hospital surgical unit 5D  
 
Single total knee replacement surgery by orthopedic surgeons Stearns, Murray, 
or Molloy 


 
5 
 
Age greater than 20 
 
Discharge to home on postoperative day one 
Excluded from the study are patients who: 
 
Have known allergy to PEG 3350 
 
Are unable to complete a follow up phone call in English 
 
Have known renal disease, irritable bowel syndrome, or inflammatory bowel 
disease (Crohn’s disease or ulcerative colitis), contraindications for PEG 3350 
use 
Sampling and Sample Size 
A convenience sample of those that agree to participate will be used. Based on prior 
research (Madsen, Magor, and Parker, 2010), the constipation rate at 3 days is expected to be 
high as high as 85% in the current standard.  In order to detect a 25% decrease in this 
constipation rate with 80% power, 49 patients per group are needed. This assumes use of two-
sided Pearson chi-square tests and a significance level of 0.05.  Since any impact of covariates 
on this outcome is unknown, this is a reasonable approximation of the power based on a logistic 
regression.  This sample size will also allow for adjustment of up to 4 covariates in our planned 
models based on recommendations of Vittinghoff and McCulloch (2007), if the event rate is 
similar to previous studies. To account for attrition, we will oversample by 50% for a total of 74 
per group or 148 total participants.  
Advertising and Recruitment 
The recruitment process will occur in two phases. Study team member Karen Sanchez 
conducts a pre-operative joint replacement patient education class for patients and their family 
members every week at Lutheran Hospital. Approximately 75% of patients having total joint 
replacement surgeries at Lutheran Hospital attend this class. She will introduce the study at the 
conclusion of the class, verbally informing potential participants about the study and providing 
the recruitment flyer to potential participants who attend the class. Participants will not be 
consented at this time so as to allow potential participants time to consider enrolling in the 
study. Recruitment flyers will be posted in all patient rooms. Prior to surgery all total knee 
arthroplasty patients of the three participating surgeons will be screened for inclusion and 
exclusion criteria by a member of the study team. On the day of surgery, a study team member 
will approach those patients who meet inclusion criteria in the preoperative unit (4B) to solicit 
participation. Study team members will review the consent document in the patient’s room prior 
to anesthesia and consent those who choose to participate using the standard signed consent 
form. 
Data Collection 
 
Study team members will gather the following information from those agreeing to 
participate: recruitment date, name, best time of day to call, best phone number to call, patient’s 
surgeon, age, sex, race/ethnicity, and whether they had a saphenous nerve block performed. 
This information will be entered into the study database in REDCap. Follow up phone calls will 
be conducted by a member of the study team beginning on postoperative day four. If the patient 
does not answer, then a total of two follow up calls can be made up through postoperative day 
seven. If the patient does not participate by day seven, they will be considered lost to follow up. 
The phone calls will follow a phone script, which starts with confirming that the participant still 
wants to answer the follow up questions. The script will be housed in REDCap so as to create a 


 
6 
database of responses as participants answer questions. After completing the survey, if the 
patient states they have not had a satisfying bowel movement, they will be instructed to 
increase their fluid and fiber consumption and use a laxative of their choosing or call their 
primary care physician or surgeon’s office to get further direction in resolving their constipation. 
 
Data needed to answer the research questions will come from two primary sources, 
patient report and abstracted from the electronic health record. All data will be gathered by 
members of the research team and entered into a REDCap database. 
 
Patient reported measures: 
o Age 
o Sex 
o Race/ethnicity 
o Bowel movement within first three post-operative days (yes/no) 
o Straining with bowel movement (0-10 numeric rating scale) 
o Discomfort with bowel movement (0-10 numeric rating scale) 
o Laxative use (yes/no) 
o Opioid analgesic use (yes/no) 
o Saphenous nerve long-acting regional block for pain control (yes/no/not sure) 
 
Electronic health record measures collected by study team members: 
o Surgeon 
o Past medical history diagnoses needed to calculate the Charlson Comorbidity 
Index Revised, as documented in the admitting problem list 
o Type of anesthesia (general vs. spinal/local) as documented in anesthesia 
OpTime record 
o Length of surgery calculated in minutes based on anesthesia OpTime record 
documented as start time of case and end time of case 
Data Analysis 
 
Intent-to-treat analysis will be used in this study. Data analyses will be conducted by a 
statistician from Quantitative Health Sciences using SAS software (version 9.3; Cary, NC) or R 
software (version 3.1; Vienna, Austria) as appropriate. Demographic characteristics will be 
reported using descriptive statistics. Categorical data will be summarized using frequencies and 
percentages, and continuous data described using means, standard deviations, and percentiles 
of interest (median, quartiles, and range). Pearson chi-square t-tests for nominal factors, 
Wilcoxon rank sum tests for ordered factors and non-normal continuous measures, and two-
sample t-tests for normal continuous measures will be used to compare treatment groups on 
collected patient and surgical characteristics. Logistic regression models will be used to assess 
differences in constipation rates between groups while adjusting for patient and surgical 
characteristics that differ between groups.  Linear regression models will be used to compare 
groups on levels of pain and straining between groups with similar adjustment.  Distributional 
assumptions of the linear mode will be tested, and if they are not met, alternative approaches, 
such as ordinal regression may be used instead. Rates of laxative and opioid use in the follow-
up period will be summarized and, if warranted, sensitivity analyses of the same analyses as 
above, omitting those who use laxatives or opioids, may be performed. 
 
 


 
7 
 
Feasibility 
The participating surgeons at Lutheran Hospital perform on average 57 total knee 
arthroplasty surgeries every month, thus making it possible to complete data collection in six 
months. The surgeons and the advanced practice providers caring for this group of patients are 
supportive of this study. Nursing administration at Lutheran Hospital is supportive of this study. 
The information gathered from participants during the follow up phone calls is purposely brief so 
as to be as minimally burdensome to the participants as possible. Study team members are 
available to make follow up phone calls from Cleveland Clinic devices. 
Limitations and Anticipated Problems 
The major limitation to this study is the single site and homogeneity that exists within the 
patient populations served by the three participating surgeons. There is also the potential for 
social desirability bias as participants respond to questions in the follow up phone call. There 
are no valid and reliable instruments that measure constipation for this population, so using 
participant self-report is the best way to quantify postoperative constipation and its symptoms. 
The primary anticipated problem in this study is losing participants to follow up. Oversampling 
should account for this loss. 
Human Subjects Protection 
 
In order to protect the confidentiality and anonymity of participants, access to the data 
will be limited to study team members and QHS staff conducting the analysis. A written informed 
consent document will be used as part of the informed consent process, and completed copies 
will be kept in a locked file drawer in the PI’s office. All data will be stored in REDCap databases 
accessible only to study team members. Collected protected health information is limited to 
those items needed to make the follow up phone call and extract data from the electronic 
medical record. All PHI will be deleted from the final database and replaced with a participant 
code number prior to analysis. This final database will be maintained electronically as the 
source of truth for this study. 


 
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